HIV

PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 13 Jul 2018)
Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS. (I)
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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 13 Jul 2018)
Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
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SMALL MOLECULE INHIBITORS OF NEUTRAL SPHINGOMYELINASE 2 (nSMase2) FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES (Fri, 13 Jul 2018)
Small molecule inhibitors of neutral sphingomyelinase 2 (nSMase2) and their use for treating neurodegenerative diseases, such as, neurodegenerative diseases associated with high levels of ceramide, including, but not limited to Alzheimer's disease (AD), HIV-associated neurocognitive disorder (HAND), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS), and, in other aspects, for treating cancer, are provided.
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ANTIVIRAL BENZYL-AMINE PHOSPHODIAMIDE COMPOUNDS (Fri, 29 Jun 2018)
Compounds of Formula I: and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
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HETEROCYCLIC COMPOUNDS AS HIV PROTEASE INHIBITORS (Fri, 29 Jun 2018)
The present invention is directed to compounds of Formula I, pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.
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HETEROCYCLIC COMPOUNDS AS HIV PROTEASE INHIBITORS (Fri, 29 Jun 2018)
The present invention is directed to compounds of Formula I pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.
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ANTIVIRAL ALIPHATIC ESTER PRODRUGS OF TENOFOVIR (Fri, 29 Jun 2018)
Compounds of Formula (I): and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.18mm" wi="55.20mm" file="US20180162831A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NITROGEN-CONTAINING TRICYCLIC DERIVATIVES HAVING HIV REPLICATION INHIBITORY ACTIVITY (Fri, 15 Jun 2018)
<p id="p-0001" num="0000">The present invention provides a novel compound having antiviral activity, especially HIV replication inhibitory activity and a medicament containing the same. The compound represented by the formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.68mm" wi="59.86mm" file="US20180162876A1-20180614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein A<sup>3 </sup>is CR<sup>3A</sup>, CR<sup>3A</sup>R<sup>3B</sup>, N or NR<sup>3C</sup>; R<sup>3A</sup>, R<sup>3B</sup>, R<sup>4A </sup>and R<sup>4B </sup>are each independently a hydrogen atom, halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkynyl, or substituted or unsubstituted non-aromatic carbocyclyl; R<sup>3C </sup>is a hydrogen atom, substituted or unsubstituted alkyl, or substituted or unsubstituted non-aromatic carbocyclyl; ring T<sup>1 </sup>is substituted or unsubstituted nitrogen-containing non-aromatic heterocycle; R<sup>1 </sup>is a hydrogen atom, halogen, cyano, or substituted or unsubstituted alkyl; R<sup>2 </sup>is each independently substituted or unsubstituted alkyl or the like: n is 1 or 2; R<sup>3 </sup>is substituted or unsubstituted aromatic carbocyclyl or the like; R<sup>4 </sup>is a hydrogen atom or a carboxy protecting group.</p>
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HETEROCYCLIC COMPOUNDS AS HIV PROTEASE INHIBITORS (Fri, 15 Jun 2018)
The present invention is directed to compounds of Formula (I), pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.
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Modulators of toll-like receptors for the treatment of HIV (Fri, 15 Jun 2018)
Provided are methods, uses, pharmaceutical regimens, pharmaceutical compositions, and kits comprising modulators of TLR7, including those of Formula 1l: Formula || and pharmaceutically acceptable salts thereof, useful in treating HIV infections.
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POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE (Fri, 08 Jun 2018)
<p id="p-0001" num="0000">Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="64.69mm" file="US20180153887A1-20180607-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">including stereoisomers and pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>, X, Y<sup>1</sup>, Y<sup>2</sup>, or L are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.</p>
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TETRACYCLIC HETEROCYCLE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS (Fri, 08 Jun 2018)
The present invention relates to Tetracyclic Heterocycle Compounds of Formula (I): (I) and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, R1, R2, R3 and R7 are as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Heterocycle Compound, and methods of using the Tetracyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.
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TRICYCLIC HETEROCYCLE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS (Fri, 08 Jun 2018)
The present invention relates to Tricyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein A, X, Y, Z, R1, R7A, R7B and R8 are as defined herein. The present invention also relates to compositions comprising at least one Tricyclic Heterocycle Compound, and methods of using the Tricyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.
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FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS (Thu, 07 Jun 2018)
The present invention relates to Fused Tricyclic Heterocycle Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 -R 8 , A, X and n are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocycle Derivative, and the Fused Tricyclic Heterocycle Derivatives for use in treating or preventing HIV infection in a subject.
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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.18mm" wi="55.20mm" file="US20180147196A1-20180531-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MONOMERIC CXCL121 PEPTIDE AND USE THEREOF (Fri, 01 Jun 2018)
<p id="p-0001" num="0000">The present invention provides a CXCL12<sub>1 </sub>peptide engineered to resist peptide-induced dimerization by maintaining steric repulsion of the chemokine helix, pharmaceutical compositions thereof, and methods of using said dimer in the treatment of cancer, inflammatory disorders, autoimmune disease, and HIV/AIDS.</p>
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HUMAN IMMUNODEFICIENCY VIRUS (HIV)-NEUTRALIZING ANTIBODIES (Thu, 24 May 2018)
The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies are characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV 1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.
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TRICYCLIC P2-LIGAND CONTAINING POTENT HIV-PROTEASE INHIBITORS AGAINST HIV/AIDS (Fri, 18 May 2018)
Various embodiments relate to a compound of the formula (I) and (II), wherein X, X1, X2, X3, and R1-R4 are defined herein, as well as pharmaceutical compositions comprising compounds of the formula (I) and/or (II) and methods of treating an HIV infection comprising administering a therapeutically effective amount of one or more compounds of formula (I) and/or (II), or a pharmaceutical composition comprising compounds of the formula (I) and/or (II), to a patient in need thereof.
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Oxolupene derivatives (Wed, 16 May 2018)
<p id="p-0001" num="0000">Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I and II:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="99.23mm" wi="69.85mm" file="US09969767-20180515-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> These compounds are useful for the treatment of HIV and AIDS. </p>
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ANTI-HIV PEPTIDES (Sat, 12 May 2018)
The present disclosure provides simple β-hairpin peptides in linear and cyclic form that specifically bind to HIV-1 Trans-Activation Response element (HIV-1 TAR), as well as compositions and use thereof.
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AGENTS AND METHODS FOR TREATING CREB BINDING PROTEIN-DEPENDENT CANCERS (Sat, 12 May 2018)
Single chain peptides comprising either a cell penetrating HIV-TAT peptide sequence and a MYB:CBP complex interfering peptide sequence from MYB, or compsiring a cell penetrating HIV-TAT peptide sequence, a CBP binding peptide sequence from CREB and a MYB:CBP complex interfering peptide sequence from MYB, are provided for use in preventing MYB:CBP complex formation and downstream events leading to cancer, in particular a leukemia. Both L-amino acid single chain peptides and retro-inverso single chain peptides are provided.
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THERAPEUTIC COMPOUNDS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Compounds disclosed herein including compounds of formula I′:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.62mm" wi="69.85mm" file="US20180127388A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and salts thereof are provided. Pharmaceutical compositions comprising compounds disclosed herein, processes for preparing compounds disclosed herein, intermediates useful for preparing compounds disclosed herein and therapeutic methods for treating an HIV infection using compounds disclosed herein are also provided.</p>
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COMPOUNDS (Fri, 11 May 2018)
<p id="p-0001" num="0000">Compounds of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.29mm" wi="59.86mm" file="US20180127405A1-20180510-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is heteroaryl optionally substituted by methyl, ethyl, halo or =0; and</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is H, methyl or ethyl. <br/> and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disease, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel disease, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure. </li> </ul> </li> </ul> </p>
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ANTI-HIV PEPTIDES (Fri, 11 May 2018)
<p id="p-0001" num="0000">The present disclosure provides simple β-hairpin peptides in linear and cyclic form that specifically bind to HIV-1 Trans-Activation Response element (HIV-1 TAR), as well as compositions and use thereof.</p>
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THERAPEUTIC COMPOUNDS (Fri, 04 May 2018)
<p id="p-0001" num="0000">Compounds disclosed herein including compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.69mm" wi="69.85mm" file="US20180118734A1-20180503-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and salts thereof are provided. Pharmaceutical compositions comprising compounds disclosed herein, processes for preparing compounds disclosed herein, intermediates useful for preparing compounds disclosed herein and therapeutic methods for treating an HIV infection using compounds disclosed herein are also provided.</p>
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ANTIVIRAL ARYL-AMIDE PHOSPHODIAMIDE COMPOUNDS (Fri, 04 May 2018)
Compounds of Formula (I): (Formula (I)) and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
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POLYCYCLICCARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE (Fri, 27 Apr 2018)
<p id="p-0001" num="0000">Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (Ia):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="63.84mm" file="US20180110776A1-20180426-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">including stereoisomers and pharmaceutically acceptable salts thereof, wherein A′, R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.</p>
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C-3 NOVEL TRITERPENONE WITH C-17 REVERSE AMIDE HETEROCYCLE DERIVATIVES AS HIV INHIBITORS (Fri, 20 Apr 2018)
The present invention relates to C-3 novel triterpenone with C-17 reverse amide heterocycle compounds of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, and n are as defined in formula (I). The invention also relates to C-3 novel triterpenone with C-17 reverse amide heterocycle derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS (Fri, 13 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.75mm" wi="62.91mm" file="US20180099967A1-20180412-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocyclic Compound, and methods of using the Fused Tricyclic Heterocyclic Compounds for treating or preventing HIV infection in a subject.</p>
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C-3 TRITERPENONE WITH C-17 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS (Fri, 13 Apr 2018)
The present invention relates to C-3 triterpenone with C-17 reverse amide compounds of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7 and 'n' are as defined in formula (I). The invention also relates to C-3 triterpenone with C-17 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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MACROHETEROCYCLIC NUCLEOSIDE DERIVATIVES AND THEIR ANALOGUES, PRODUCTION AND USE THEREOF (Fri, 13 Apr 2018)
The present invention relates to macroheterocyclic nucleoside derivatives and their analogues, production and use thereof. These compounds are the prodrugs for treating viral and cancerous diseases and are inhibitors of HCV NS5B polymerase, HBV DNA polimerase and HIV-I reverse transcriptase (RT).
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HIV-1 ENV FUSION PEPTIDE IMMUNOGENS AND THEIR USE (Fri, 13 Apr 2018)
Embodiments of immunogens based on the HIV-1 Env fusion peptide and methods of their use and production are disclosed. Nucleic acid molecules encoding the immunogens are also provided. In several embodiments, the immunogens can be used to generate an immune response to HIV-1 Env in a subject, for example, to treat or prevent an HIV-1 infection in the subject.
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CRYSTALLINE FORMS OF MODIFIED TRITERPENOID HYDROCHLORIDE SALTS WITH HIV MATURATION INHIBITOR ACTIVITY (Fri, 06 Apr 2018)
<p id="p-0001" num="0000">The present invention relates to crystalline forms of modified triterpenoid hydrochloride salts with HIV maturation inhibitor activity. More specifically, the present invention relates to the H-4, T1F-1, and T1F-2 crystalline forms. The present invention also relates to pharmaceutical compositions comprising these crystalline forms, as well as to methods of using these crystalline forms for the treatment of the HIV virus, and methods for obtaining these crystalline forms.</p>
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BENZOTHIAZOL-6-YL ACETIC ACID DERIVATIVES AND THEIR USE FOR TREATING HIV INFECTION (Fri, 06 Apr 2018)
Compounds disclosed herein including compounds of Formula I: and salts thereof are provided. Pharmaceutical compositions comprising compounds disclosed herein, processes for preparing compounds disclosed herein, intermediates useful for preparing compounds disclosed herein and therapeutic methods for treating an HIV infection using compounds disclosed herein are also provided.
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CONSTRUCTS TARGETING HIV PEPTIDE/MHC COMPLEXES AND USES THEREOF (Fri, 30 Mar 2018)
The present application provides constructs comprising an antibody moiety that specifically bind to a complex comprising a human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT) peptide and an MHC class I protein. Also provided are methods of making and using these constructs.
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OLIGONUCLEOTIDES CONTAINING 2'-DEOXY-2'FLUORO-BETA-D-ARABINOSE NUCLEIC ACID (2'-FANA) FOR TREATMENT AND DIAGNOSIS OF RETROVIRAL DISEASES (Fri, 30 Mar 2018)
The disclosure relates to synthetic oligonucleotides that bind at least a portion of a dimerization initiation site (DIS) of a retrovirus genomic ribonucleic acid (RNA) molecule. In some aspects, the synthetic oligonucleotides include a 2-deoxy-2-fluoroarabinonucleotide (2- FANA)-modified nucleotide sequence. In some embodiments, the 2-FANA-modified nucleotide sequence inhibits dimerization of retroviral genomes (e.g., an HIV genome). Other embodiments include methods of inhibiting expression of a retrovirus using the synthetic oligonucleotide, and methods of treating or preventing a retroviral infection.
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PROCESSES AND INTERMEDIATES FOR PREPARING ANTI-HIV AGENTS (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties.</p>
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SALTS OF HIV INHIBITOR COMPOUNDS (Fri, 23 Mar 2018)
<p id="p-0001" num="0000">The invention is related to salts of anti-viral compounds, compositions containing such salts, and therapeutic methods that include the administration of such salts, as well as to process and intermediates useful for preparing such salts.</p>
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BENZIMIDAZOL DERIVATIVES FOR TREATING FILOVIRUS INFECTION (Fri, 23 Mar 2018)
The present invention relates to compounds comprising a benzimidazole scaffold, and the use of such compounds for the treatment of viral diseases. The invention also relates to pharmaceutical compositions comprising said compounds as an active ingredient. In particular the compounds of the invention comprising a benzimidazole scaffold are used for the treatment of filoviruses or retroviruses, and preferably for the treatment of Ebola virus or HIV virus.
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BENZIMIDAZOL DERIVATIVES FOR TREATING FILOVIRUS INFECTION (Thu, 22 Mar 2018)
The present invention relates to compounds comprising a benzimidazole scaffold, and the use of such compounds for the treatment of viral diseases. The invention also relates to pharmaceutical compositions comprising said compounds as an active ingredient. In particular the compounds of the invention comprising a benzimidazole scaffold are used for the treatment of filoviruses or retroviruses, and preferably for the treatment of Ebola virus or HIV virus.
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COMBINATIONS COMPRISING 5-PHENOXY-3H-PYRIMIDIN-4-ONE DERIVATIVES AND THEIR USE FOR THE PROPHYLAXIS OR TREATMENT OF INFECTION BY HIV (Thu, 22 Mar 2018)
The invention relates to a combination comprising an effective amount of (i) a 5-phenoxy-3H-pyrimidin-4-one derivative of Formula I: or a pharmaceutically acceptable salt thereof wherein M is CH2, CH 2 CH 2 , CH 2 CH 2 CH 2 , CH(CH 3 ), C(CH 3 ) 2 or C(O)N(R A ), and Z is selected from the group consisting of: pyridazine, pyridazinone, pyrimidine, pyrimidinone, pyrazine, pyrazinone, triazine and triazinone, each optionally substituted with one or more substituents up to the maximum number allowed by valence selected from R 4 and R 5 , and (ii) one or more anti-HIV agent(s). The invention further relates to use of said combination for the prophylaxis or treatment of infection by HIV or for the prophylaxis, treatment, or delay in the onset of AIDS in a subject.
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INHIBITORS OF HISTONE DEACETYLASE (Fri, 16 Mar 2018)
<p id="p-0001" num="0000">The present invention relates to compounds of formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.48mm" wi="64.18mm" file="US20180072671A1-20180315-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein X<sub>1</sub>, X<sub>2</sub>, X<sub>3</sub>, X<sub>4</sub>, X<sub>5</sub>, W<sub>1</sub>, W<sub>2</sub>, W<sub>3</sub>, and W<sub>4 </sub>are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. In one aspect, the invention relates to selective HDAC3 inhibitors useful for protecting β-cells and improving insulin resistence. The selective HDAC3 inhibitors are also useful for promoting cognitive function and enhancing learning and memory formation. Compounds of the invention are useful for treating, alleviating, and/or preventing various conditions, including for example, a metabolic disorder such as type 1 or type 2 diabetes, dyslipidemias, lipodystrophies, liver disease associated with metabolic syndrome, polycystic ovarian syndrome, or obesity; inflammatory disease; neurological disorder; a memory or cognitive function disorder/impairment; an extinction learning disorder; fungal disease or infection; viral disease or infection such as HIV; hematological disease; liver disease; lysosomal storage disease; or neoplastic disease in humans or animals.</p>
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INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 16 Mar 2018)
<p id="p-0001" num="0000">Compounds of Formulas I-VI, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth. Formula I is exemplified below:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.92mm" wi="65.70mm" file="US20180072997A1-20180315-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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FUNCTIONAL CURE OF RETROVIRAL INFECTION (Fri, 16 Mar 2018)
<p id="p-0001" num="0000">The application relates to methods of curing retroviral infections, i.e. ensuring remission of retroviral infections, more particularly HIV infections, by administering a compound which is capable of binding to the LEDGF/p75 binding pocket of HIV-integrase and inhibiting LEDGF/p75-IN protein-protein interaction. The application further relates to the use of LEDGINs in retroviral gene therapy.</p>
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HIV CLINICAL PLAN (Fri, 16 Mar 2018)
A method of performing a clinical trial for a gene editing or gene excising system for treating HIV in humans, by recruiting HIV infected individuals currently receiving highly active antiretroviral therapy (HAART) that is effective in lowering viral load, administering the gene editing or gene excising system treatment to the individuals in Phase 1a, Phase 1b, and Phase 1c, and performing assays to confirm HIV viral genome excision from the individuals' cells.
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Extended betulinic acid analogs (Wed, 14 Mar 2018)
<p id="p-0001" num="0000">Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I and II:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="98.13mm" wi="70.10mm" file="US09914747-20180313-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> These compounds are useful for the treatment of HIV and AIDS. </p>
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Miliusanes As Antiviral Agents (Fri, 09 Mar 2018)
<p id="p-0001" num="0000">The present disclosure relates to miliusane and analogs thereof that are useful as anti-virals, such as anti-HIV and anti-influenza virus agents. The present disclosure provides methods for treating viral infections, such as AIDS, HIV, and influenza infections.</p>
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ANTIVIRAL BETA-AMINO ACID ESTER PHOSPHODIAMIDE COMPOUNDS (Fri, 09 Mar 2018)
<p id="p-0001" num="0000">Compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.22mm" wi="69.93mm" file="US20180065999A1-20180308-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.</p>
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TOLL LIKE RECEPTOR MODULATOR COMPOUNDS (Fri, 09 Mar 2018)
This application relates to toll like receptor modulator (e.g. TLR8) compounds of Formula I and pharmaceutical compositions containing them. The compounds are useful for the treatment of hyperproliferative diseases such as cancer or viral infections such as hepatitis B and HIV.
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HIV-1 NUCLEOCAPSID INHIBITORS (Thu, 08 Mar 2018)
The present invention discloses novel anti-HIV agents targeting the HIV Nucleocapsid protein (NC), which is one of the most conserved sequences within HIV strains and is highly required for HIV replication. The compounds of the invention are particularly useful to overcome antiretroviral drug-resistance in HIV-1 infected individuals.
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BROADLY NEUTRALIZING HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) GP120-SPECIFIC MONOCLONAL ANTIBODY (Fri, 02 Mar 2018)
<p id="p-0001" num="0000">The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.</p>
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ANTIVIRAL PRODRUGS OF TENOFOVIR (Fri, 02 Mar 2018)
Compounds of Formula I: and pharmaceutically acceptable salts and co-crystals thereof are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
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COMBINATIONS COMPRISING A 4-ISOQUINOLONE DERIVATIVE AND PROTEASE INHIBITORS (Thu, 01 Mar 2018)
The present invention relates to a combination therapy for treating an HIV infection or inhibiting integrase comprising (S)-6-(3-chloro-2-fluorobenzyl)-1-(1-hydroxymethyl-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ("Compound A") or a pharmaceutically acceptable solvate or salt thereof in combination with at least one other anti-HIV agent. In some embodiments of the present invention, the other anti-HIV agents are chosen from reverse transcriptase inhibitors and protease inhibitors. In certain embodiments of the present invention, the other anti-HIV agents are chosen from AZT, 3TC, PMPA, efavirenz, indinavir, nelfinavir, a combination of AZT/3TC, and a combination of PMPA/3TC. Since Compound A has a high inhibitory activity specific for integrases, when used in combinations with other anti-HIV agents it can provide a combination therapy with fewer side effects for humans.
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THERAPEUTIC COMPOUNDS (Fri, 23 Feb 2018)
<p id="p-0001" num="0000">The present disclosure relates to a compound of formula (Ia), (Ib), (IIa), and (IIb):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="210.74mm" wi="75.69mm" file="US20180051005A1-20180222-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="66.04mm" wi="75.69mm" file="US20180051005A1-20180222-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">which are useful in the treatment of a Retroviridae viral infection including an infection caused by the HIV virus.</p>
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PHOSPHATE SUBSTITUTED QUINOLIZINE DERIVATIVES USEFUL AS HIV INTEGRASE INHIBITORS (Fri, 23 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to Phosphate Substituted Quinolizine Derivatives of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>9 </sup>and R<sup>10 </sup>are as defined herein. The present invention also relates to compositions comprising at least one Phosphate Substituted Quinolizine Derivative, and methods of using the Phosphate Substituted Quinolizine Derivatives for treating or preventing HIV infection in a subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.86mm" wi="69.85mm" file="US20180051043A1-20180222-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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THERAPEUTIC COMPOUNDS USEFUL FOR THE PROPHYLACTIC OR THERAPEUTIC TREATMENT OF AN HIV VIRUS INFECTION (Fri, 23 Feb 2018)
The present disclosure relates to a compound of formula (Ia), (Ib), (IIa), and (IIb): (Ia) (Ib) (IIa) (IIb) which are useful in the treatment of a Retroviridae viral infection including an infection caused by the HIV virus.
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Thu, 22 Feb 2018)
The present invention is to provide a novel compound (I-1) shown below, having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof. wherein A ring is substituted ring of (a), (b) or (c) wherein Z is O or NR 19 , R 19 is hydrogen, C 1-10 alkyl, C 2-8 alkenyl, C 1-10 alkylcarbonyl or C 1-10 alkylsulfonyl, and the other substituents on the A ring form a ring; R 14 and R X are hydrogen; a broken line represents the presence or absence of a bond, provided that when the broken line represents the presence of a bond, R X is not present; R 1 is hydrogen or C 1-10 alkyl; X is C 1-6 alkylene; R 2 is phenyl or phenyl substituted with at least halogen; R 3 is hydrogen, halogen, hydroxy, C 1-10 alkyl, C 2-8 alkenyl, C 1-10 alkoxy, C 2-8 alkenyloxy or amino; or a pharmaceutically acceptable salt, or solvate thereof.
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Thu, 22 Feb 2018)
The present invention is to provide a novel compound shown below, having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug. wherein A ring is unsubstituted heterocycle; R 14 and R X are hydrogen; a broken line represents the absence of a bond; R 1 is hydrogen or C 1-10 alkyl; X is C 1-6 alkylene; R 2 is phenyl or phenyl substituted with at least halogen; and R 3 is hydrogen, halogen, hydroxy, C 1-10 alkyl, C 2-8 alkenyl, C 1-10 alkoxy, C 2-8 alkenyloxy or amino; or a pharmaceutically acceptable salt, or solvate thereof.
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4-AMINO-3-PHENYLAMINO-6-PHENYLPYRAZOLO[3,4-D]PYRIMIDINE DERIVATIVES FOR USE AS BCRP INHIBITORS IN THERAPEUTIC TREATMENTS (Fri, 16 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to 5-amino-3-phenylamino-6-phenylpyrazolo[3,4-d]pyrimidine derivatives of the general formula (I) or pharmaceutically acceptable salts or propharmacons thereof for use as BCRP inhibitors, wherein at least one hydrogen atom in at least one of the phenyl groups A and B is substituted by a substituent R<sup>H</sup>, which has a Hammett constant σ<sub>p </sub>greater than 0.23. For corresponding compounds, surprisingly a particularly high inhibitory activity against BCRP has been discovered which can be exploited for suppressing the multidrug resistance modulator BCRP, thus providing an improvement in efficacy of BCRP affected drugs. This has useful implications for cancer and HIV treatment.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.64mm" wi="69.85mm" file="US20180044341A1-20180215-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHODS OF PRODUCING COMPOUNDS HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 16 Feb 2018)
<p id="p-0001" num="0000">A process for preparing a compound represented by formula (Y1) or (Y2) [wherein IV is an optionally substituted carbocyclyl lower alkyl, or the like] or a salt thereof, using a novel process for preparing a pyridone derivative represented by formula (X4) [wherein R<sup>1d </sup>is hydrogen, halogen, or the like; R<sup>2d </sup>is hydrogen, a lower alkyl optionally substituted with substituent E, or the like; R<sup>4d </sup>is a lower alkyl optionally substituted with substituent E, or the like; and R<sup>6d </sup>is a lower alkyl group optionally substituted with substituent group E, or the like].</p>
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C-3 NOVEL TRITERPENONE WITH C-17 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS (Fri, 16 Feb 2018)
The present invention relates to C-3 novel triterpenone with C-17 reverse amide compounds of Formula (I); and pharmaceutically acceptable salts thereof, wherein ring Formula (II), R1, R2, R3, R4, R5, R6, R7, 'n' and 'm' are as defined in Formula (I). The invention also relates to C-3 novel triterpenone with C-17 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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C-3 NOVEL TRITERPENONE WITH C-17 N-AMIDE DERIVATIVES AS HIV INHIBITORS (Fri, 16 Feb 2018)
The present invention relates to C-3 novel triterpenone with C-17 N-amide compounds of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6 and 'X' are as defined in formula (I). The invention also relates to compounds of formula (I), its related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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C-3 NOVEL TRITERPENONE WITH C-28 HETEROCYCLE DERIVATIVES AS HIV INHIBITORS (Fri, 16 Feb 2018)
The present invention relates to C-3 novel triterpenone with C-28 heterocycle compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R1, W, ring X and ring Y are as defined in formula (I). The present invention comprising compound of formula (I) and related compounds, compositions are useful for therapeutic treatment of viral diseases, particularly HIV mediated diseases.
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Processes and intermediates for preparing anti-HIV agents (Fri, 16 Feb 2018)
The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties.
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METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF HIV INFECTION (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to methods and pharmaceutical compositions for the treatment of HIV infection. In particular, the present invention relates to a method of treating HIV infection in a subject in need thereof comprising administering the subject with a therapeutically effective amount of the oligonucleotide comprising the sequence as set forth in SEQ ID NO:</p>
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METHODS OF PRODUCING COMPOUNDS HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 09 Feb 2018)
<p id="p-0001" num="0000">A process for preparing a compound represented by formula (Y1) or (Y2) [wherein R<sup>x </sup>is an optionally substituted carbocyclyl lower alkyl, or the like] or a salt thereof, using a novel process for preparing a pyridone derivative represented by formula (X4) [wherein R<sup>1d </sup>is hydrogen, halogen, or the like; R<sup>2d </sup>is hydrogen, a lower alkyl optionally substituted with substituent E, or the like; R<sup>4d </sup>is a lower alkyl optionally substituted with substituent E, or the like; and R<sup>6d </sup>is a lower alkyl group optionally substituted with substituent group E, or the like].</p>
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C-3 NOVEL TRITERPENONE WITH C-28 DIAMIDE DERIVATIVES AS HIV INHIBITORS (Fri, 09 Feb 2018)
The present invention relates to C-3 novel triterpenone with C-28 diamide compounds of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6 and 'm' are as defined in formula (I). The present invention also relates to compounds of formula (I) and their related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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Phosphoramidate nucleoside prodrug for treating viral diseases and cancer, processes for their preparation and their use (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer.</p> <p id="p-0002" num="0000">The phosphoramidate nucleoside prodrug of the general formula 1, a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof,</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.45mm" wi="53.51mm" file="US20180030080A1-20180201-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein: Ar is aryl or hetaryl; R<sup>1 </sup>is H or CH<sub>3</sub>; R<sup>2 </sup>is the substituent selected from OCH<sub>2</sub>CH═CH<sub>2</sub>, OCH<sub>2</sub>CH≡CH, OCH<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>OCH<sub>3</sub>,</p> <p id="p-0005" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="39.20mm" wi="52.32mm" file="US20180030080A1-20180201-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0006" num="0000">R<sup>3 </sup>is H or CH<sub>3</sub>; R<sup>4 </sup>is OH, OR<sup>5</sup>, NR<sup>6</sup>R<sup>7</sup>; R<sup>5 </sup>is C<sub>1</sub>-C<sub>4</sub>-alkyl; R<sup>6 </sup>and R<sup>7 </sup>are not necessarily the same substituents selected from H or CH<sub>3</sub>; Z═O, or NH; an arrow (→) indicates the place of substituent connection; <br/> Nuc is </p> <p id="p-0007" num="0000"><chemistry id="CHEM-US-00003" num="00003"> <img id="EMI-C00003" he="29.89mm" wi="62.82mm" file="US20180030080A1-20180201-C00003.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0008" num="0000">R<sup>8 </sup>and R<sup>9 </sup>are not necessarily the same substituents selected from H, F, Cl, CH<sub>3 </sub>or OH provided when continuous line and its accompanying dotted line (<img id="CUSTOM-CHARACTER-00001" he="2.46mm" wi="6.35mm" file="US20180030080A1-20180201-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/>) together are the single carbon-carbon (C—C) bond or R<sup>8 </sup>and R<sup>9 </sup>are hydrogen provided when continuous line and its accompanying dotted line (<img id="CUSTOM-CHARACTER-00002" he="2.46mm" wi="6.35mm" file="US20180030080A1-20180201-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/>) together are the double carbon-carbon bond (C═C); <br/> R<sup>10 </sup>is the substituent selected from R<sup>10.1</sup>-R<sup>10.5</sup>; </p> <p id="p-0009" num="0000"><chemistry id="CHEM-US-00004" num="00004"> <img id="EMI-C00004" he="131.66mm" wi="56.39mm" file="US20180030080A1-20180201-C00004.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0010" num="0000">R<sup>11 </sup>is the substituent selected from H, F, Cl, CH<sub>3</sub>, or CF<sub>3</sub>; <br/> R<sup>12 </sup>is hydrogen, C<sub>1</sub>-C<sub>4</sub>-alkyl or C<sub>3</sub>-C<sub>6</sub>-cycloalkyl; <br/> X is oxygen or ethanediyl-1,1 (C═CH<sub>2</sub>); <br/> Y is O, S, CH<sub>2</sub>, or HO—CH group provided when continuous line and its accompanying dotted line (<img id="CUSTOM-CHARACTER-00003" he="2.46mm" wi="6.35mm" file="US20180030080A1-20180201-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/>) together are the single carbon-carbon (C—C) bond or Y is CH group provided when continuous line and its accompanying dotted line (<img id="CUSTOM-CHARACTER-00004" he="2.46mm" wi="6.35mm" file="US20180030080A1-20180201-P00001.TIF" alt="custom-character" img-content="character" img-format="tif"/>) together are the double carbon-carbon bond (C═C), and compound of the general formula 1, stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, wherein: <br/> Ar is aryl or hetaryl; <br/> R<sup>1 </sup>is H or CH<sub>3</sub>; <br/> R is isopropyl; <br/> Nuc is </p> <p id="p-0011" num="0000"><chemistry id="CHEM-US-00005" num="00005"> <img id="EMI-C00005" he="74.59mm" wi="48.77mm" file="US20180030080A1-20180201-C00005.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SUBSTITUTED QUINOLIZINE DERIVATIVES USEFUL AS HIV INTEGRASE INHIBITORS (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to Substituted Quinolizine Derivatives of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="60.79mm" file="US20180028509A1-20180201-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>9 </sup>and R<sup>10 </sup>are as defined herein. The present invention also relates to compositions comprising at least one Substituted Quinolizine Derivative, and methods of using the Substituted Quinolizine Derivatives for treating or preventing HIV infection in a subject.</p>
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3-HYDROXYPYRIMIDINE-2,4-DIONE-5-CARBOXAMIDES AS POTENT INHIBITORS OF HIV (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Various embodiments described herein are directed to compounds of formula (I), (II), (III) or (IV) for use as potent inhibitors of HIV integrase and for treatment of patients afflicted with AIDS. A major challenge of human immunodeficiency virus (HIV) chemotherapy continues to be the inevitable selection of resistance by the virus towards known drug regimens. Treating resistant HIV strains calls for novel antivirals with unique structural cores. Some embodiments are directed to compounds featuring a 3-hydroxypyrimidine-2,4-dione-5-carboxamide core that consistently confers low nanomolar potencies against HIV-1 in cell culture. Biochemical testing and molecular modeling results corroborate an antiviral mechanism of action of inhibiting integrase strand transfer (INST). Preliminary testing against raltegravir-resistant HIVs showed marginal cross resistance, suggesting that the chemotypes of the various embodiments described herein could fit an inhibitory profile of second generation INSTIs.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="134.20mm" wi="57.15mm" file="US20180028535A1-20180201-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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A NEW QUINOLINE DERIVATIVE FOR USE IN THE TREATMENT AND PREVENTION OF VIRAL INFECTIONS (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">The present invention relates to a quinoline derivative of formula (1) or one of its pharmaceutically acceptable salts. The present invention further relates to said quinoline derivative for medicament and for use in the treatment or prevention of a viral or retroviral infection and in particular AIDS or an AIDS-related condition or Human Immunodeficiency virus (HIV). The present invention also relates to a pharmaceutical composition comprising said quinoline derivative and to the process for preparing it as to a novel intermediate compound.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="45.72mm" wi="66.63mm" file="US20180030078A1-20180201-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Selective HDAC1 and HDAC2 inhibitors (Fri, 02 Feb 2018)
<p id="p-0001" num="0000">Provided herein are compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with HDAC activity, particularly diseases or disorders that involve activity of HDAC1 and/or HDAC2. Such diseases include cancer, sickle-cell anemia, beta-thalassemia, and HIV.</p>
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PHOSPHORAMIDATE NUCLEOSIDE PRODRUG FOR TREATING VIRAL DISEASES AND CANCER, PROCESSES FOR THEIR PREPARATION AND THEIR USE (Fri, 02 Feb 2018)
The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer. The phosphoramidate nucleoside prodrug of the general formula (1), a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, formula (1) wherein: Ar is aryl or hetaryl; R1 is H or CH3, R2 is the substituent selected from OCH2CH=CH2, OCH2CH≡CH, OCH2CH2CH2OCH3, formula (2), formula (3) or formula (4), R3 is H or CH3; R4 is OH, OR5, NR6R7; R5 is C1-C4-alkyl; R6 and R7 are not necessarily the same substituents selected from H or CH3, Z = O, or NH; an arrow (→) indicates the place of substituent connection; Nuc is formula (5) or (6); R8 and R9 are not necessarily the same substituents selected from H, F, Cl, CH3 or OH provided when continuous line and its accompanying dotted line ( ) together are the single carbon-carbon (C-C) bond or R8 and R9 are hydrogen provided when continuous line and its accompanying dotted line ( ) together are the double carbon-carbon bond (C=C); R10 is the substituent selected from R10.1- R10.5; R10.1 R10.2 R10.4 R10.5 ; R11 is the substituent selected from H, F, CI, CH3, or CF3; R12 is hydrogen, C1-C4-alkyl or C3-C6-cycloalkyl; X is oxygen or ethanediyl-1,1 (C=CH2); Y is O, S, CH2, or HO-CH group provided when continuous line and its accompanying dotted line (formula 7) together are the single carbon-carbon (C-C) bond or Y is CH group provided when continuous line and its accompanying dotted line (formula 7) together are the double carbon-carbon bond (C=C), and compound of the general formula (1), stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, wherein: Ar is aryl or hetaryl; R1 is H or CH3; R2 is isopropyl; Nuc is formula (8), (9) or (10).
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A NOVEL PROCESS FOR THE PREPARATION OF HIV PROTEASE INHIBITOR AND INTERMEDIATES THEREOF (Fri, 26 Jan 2018)
The present invention relates to process for the preparation of Darunavir or a solvate thereof of Formula (I) using a novel intermediate (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (2S,3R)-4-(4-(1,3-dioxoisoindolin-2-yl)-N-isobutylphenylsulfonamido)-3 -hydroxy- 1 -phenylbutan-2- ylcarbamate Compound of formula (II): The present invention also relates to the process for the preparation of novel intermediates (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl (2S,3R)-4-(4-(l,3-dioxo iso indolin-2-yl)-N-isobutylphenylsulfonamido)-3 -hydroxy-1-phenylbutan-2-ylcarbamate Compound of formula (II). Darunavir or its solvate of formula (I) are useful therapeutic agent and used in treatment of antiviral diseases.
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氨基酸骨架类新型CXCR4拮抗剂及其制备与生物医学应用 (Sat, 20 Jan 2018)
本发明提出了式(I)所表示化合物或其药学上可接受的盐或前药。该化合物,结构新颖、高效低毒且具有优异CXCR4拮抗活性,能阻断HIV入侵感染人体靶细胞或治疗或预防艾滋病或动员人体骨髓造血细胞、间充质干细胞及干细胞或干扰CXCL12/CXCR4介导的细胞迁移和粘附或预防、治疗由CXCR4介导的肿瘤转移、侵袭及生长或阻断CXCL12/CXCR4介导的自身免疫性和炎性反应;且该类化合物可作为药物组合物中的有效成分能与其他抗HIV药物联用来预防、治疗HIV或者与其它用于治疗或与预防白血病、淋巴瘤、骨髓瘤以及实体瘤的药物联用来预防、治疗肿瘤。
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COMPOUNDS AND METHODS FOR TREATING HIV INFECTION (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">Provided herein, inter alia, are methods and compounds for treating an HIV infection.</p>
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HIV INHIBITING BICYCLIC PYRIMIDINE DERIVATIVES (Fri, 19 Jan 2018)
<p id="p-0001" num="0000">HIV replication inhibitors of formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.61mm" wi="69.85mm" file="US20180016281A1-20180118-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">N-oxides, pharmaceutically acceptable addition salts, quaternary amines or stereoisomeric forms thereof, wherein</li> <li id="ul0002-0002" num="0000">-a<sup>1</sup>=a<sup>2</sup>=a<sup>3</sup>=a<sup>4</sup>- is —CH═CH—CH═CH—, —N═CH—CH═CH—, —N═CH—N═CH—, —N═CH—CH═N—, —N═N—CH═CH—; -b<sup>1</sup>=b<sup>2</sup>-b<sup>3</sup>=b<sup>4</sup>- is —CH═CH—CH═CH—, —N═CH—CH═CH—, —N═CH—N═CH—, —N═CH—CH═N—, —N═N—CH═CH—;</li> <li id="ul0002-0003" num="0000">n and m is 0, 1, 2, 3 and in certain cases also 4;</li> <li id="ul0002-0004" num="0000">R<sup>1 </sup>is hydrogen; aryl; formyl; C<sub>1-6</sub>alkylcarbonyl; optionally substituted C<sub>1-6</sub>alkyl; C<sub>1-6</sub>alkyloxycarbonyl;</li> <li id="ul0002-0005" num="0000">R<sup>2 </sup>is OH; halo; optionally substituted C<sub>1-6</sub>alkyl, C<sub>2-6</sub>alkenyl or C<sub>2-6</sub>alkynyl; substituted carbonyl; carboxyl; CN; nitro; amino; substituted amino; polyhalomethyl; polyhalomethylthio; —S(=O)<sub>p</sub>R<sup>6</sup>; C(═NH)R<sup>6</sup>;</li> <li id="ul0002-0006" num="0000">R<sup>2a </sup>is CN; amino; substituted amino; optionally substituted C<sub>1-6</sub>alkyl; halo; optionally substituted C<sub>1-6</sub>alkyloxy; substituted carbonyl; —CH═N—NH—C(═O)—R<sup>16</sup>; optionally substituted C<sub>1-6</sub>alkyloxyC<sub>1-6</sub>alkyl; substituted C<sub>2-6</sub>alkenyl or C<sub>2-6</sub>alkynyl; —C(═N—O—R<sup>8</sup>)—C<sub>1-4</sub>alkyl; R<sup>7 </sup>or —X—R<sup>7</sup>;</li> <li id="ul0002-0007" num="0000">R<sup>3 </sup>is CN; amino; C<sub>1-6</sub>alkyl; halo; optionally substituted C<sub>1-6</sub>alkyloxy; substituted carbonyl; —CH═N—NH—C(═O)—R<sup>16</sup>; substituted C<sub>1-6</sub>alkyl; optionally substituted C<sub>1-6</sub>alkyloxyC<sub>1-6</sub>alkyl; substituted C<sub>2-6</sub>alkenyl or C<sub>2-6</sub>alkynyl; —C(═N—O—R<sup>8</sup>)—C<sub>1-4</sub>alkyl; R<sup>7</sup>; —X—R<sup>7</sup>;</li> <li id="ul0002-0008" num="0000">R<sup>4 </sup>is halo; OH; optionally substituted C<sub>1-6</sub>alkyl, C<sub>2-6</sub>alkenyl or C<sub>2-6</sub>alkynyl; C<sub>3-7</sub>cycloalkyl; C<sub>1-6</sub>alkyloxy; CN; nitro; polyhaloC<sub>1-6</sub>alkyl; polyhaloC<sub>1-6</sub>alkyloxy; substituted carbonyl; formyl; amino; mono- or di(C<sub>1-4</sub>alkyl)amino or R<sup>7</sup>;</li> <li id="ul0002-0009" num="0000">-A-B- is —CR<sup>5</sup>═N—, —N═N—, —CH<sub>2</sub>—CH<sub>2</sub>—, —CS—NH—, —CO—NH—, —CH═CH—;</li> <li id="ul0002-0010" num="0000">pharmaceutical compositions comprising these; methods for the preparation of these compounds and compositions; the use of these compounds for the prevention or the treatment of HIV infection.</li> </ul> </li> </ul> </p>
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HIV INHIBITING BICYCLIC PYRIMIDINE DERIVATIVES (Fri, 12 Jan 2018)
<p id="p-0001" num="0000">HIV replication inhibitors of formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.30mm" wi="69.85mm" file="US20180009819A1-20180111-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">N-oxides, pharmaceutically acceptable addition salts, quaternary amines or stereoisomeric forms thereof, wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">-a<sup>1</sup>=a<sup>2</sup>-a<sup>3</sup>=a<sup>4</sup>- is —CH═CH—CH═CH—, —N═CH—CH═CH—, —N═CH—N═CH—, —N═CH—CH═N—, —N═N—CH═CH—; -b<sup>1</sup>=b<sup>2</sup>-b<sup>3</sup>=b<sup>4</sup>- is —CH═CH—CH═CH—, —N═CH—CH═CH—, —N═CH—N═CH—, —N═CH—CH═N—, —N═N—CH═CH—;</li> <li id="ul0001-0002" num="0000">n and m is 0, 1, 2, 3 and in certain cases also 4;</li> <li id="ul0001-0003" num="0000">R<sup>1 </sup>is hydrogen; aryl; formyl; C<sub>1-6</sub>alkylcarbonyl; optionally substituted C<sub>1-6</sub>alkyl; C<sub>1-6</sub>alkyloxycarbonyl;</li> <li id="ul0001-0004" num="0000">R<sup>2 </sup>is OH; halo; optionally substituted C<sub>1-6</sub>alkyl, C<sub>2-6</sub>alkenyl or C<sub>2-6</sub>alkynyl; substituted carbonyl; carboxyl; CN; nitro; amino; substituted amino; polyhalomethyl; polyhalomethylthio; —S(═O)<sub>p</sub>R<sup>6</sup>; C(═NH)R<sup>6</sup>;</li> <li id="ul0001-0005" num="0000">R<sup>2a </sup>is CN; amino; substituted amino; optionally substituted C<sub>1-6</sub>alkyl; halo; optionally substituted C<sub>1-6</sub>alkyloxy; substituted carbonyl; —CH═N—NH—C(═O)—R<sup>16</sup>; optionally substituted C<sub>1-6</sub>alkyloxyC<sub>1-6</sub>alkyl; substituted C<sub>2-6</sub>alkenyl or C<sub>2-6</sub>alkynyl; —C(═N—O—R<sup>8</sup>)—C<sub>1-4</sub>alkyl; R<sup>7 </sup>or X—R<sup>7</sup>;</li> <li id="ul0001-0006" num="0000">R<sup>3 </sup>is CN; amino; C<sub>1-6</sub>alkyl; halo; optionally substituted C<sub>1-6</sub>alkyloxy; substituted carbonyl; —CH═N—NH—C(═O)—R<sup>16</sup>; substituted C<sub>1-6</sub>alkyl; optionally substituted C<sub>1-6</sub>alkyloxyC<sub>1-6</sub>alkyl; substituted C<sub>2-6</sub>alkenyl or C<sub>2-6</sub>alkynyl; —C(═N—O—R<sup>8</sup>)—C<sub>1-4</sub>alkyl; R<sup>7</sup>; —X—R<sup>7</sup>;</li> <li id="ul0001-0007" num="0000">R<sup>4 </sup>is halo; OH; optionally substituted C<sub>1-6</sub>alkyl, C<sub>2-6</sub>alkenyl or C<sub>2-6</sub>alkynyl; C<sub>3-7</sub>cycloalkyl; C<sub>1-6</sub>alkyloxy; CN; nitro; polyhaloC<sub>1-6</sub>alkyl; polyhaloC<sub>1-6</sub>alkyloxy; substituted carbonyl; formyl; amino; mono- or di(C<sub>1-4</sub>alkyl)amino or R<sup>7</sup>;</li> <li id="ul0001-0008" num="0000">-A-B— is —CR<sup>5</sup>═N—, —N═N—, —CH<sub>2</sub>—CH<sub>2</sub>—, —CS—NH—, —CO—NH—, —CH═CH—; <br/> pharmaceutical compositions comprising these; methods for the preparation of these compounds and compositions; the use of these compounds for the prevention or the treatment of HIV infection. </li> </ul> </p>
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ALKALOIDS FROM SPONGE, SCAFFOLDS FOR THE INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Anti-viral compounds with low cytotoxicity are identified from screening of products found in Red Sea sponges, including the sponge Stylissa carteri. The identified compounds can be brominated pyrrole-2-aminoimidazole alkaloids and derivatives thereof. Specific examples of identified compounds include oroidin, hymenialdisine, and debromohymenialdisine, as well as derivatives thereof. The compounds also can be useful scaffolds or pharmacores for further chemical modification and derivatization. Selected compounds, particularly oroidin, show selective anti-viral HIV-1 activity coupled with reduced cytotoxicity. The compounds can function as HIV reverse-transcriptase inhibitors, and molecular modeling can be used to confirm inhibition.</p>
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SALTS OF PRODRUGS OF PIPERAZINE AND SUBSTITUTED PIPERIDINE ANTIVIRAL AGENTS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.24mm" wi="69.85mm" file="US20180000849A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">X is C or N with the proviso that when X is N, R<sup>1 </sup>does not exist;</li> <li id="ul0002-0003" num="0000">W is C or N with the proviso that when W is N, R<sup>2 </sup>does not exist;</li> <li id="ul0002-0004" num="0000">V is C;</li> <li id="ul0002-0005" num="0000">E is hydrogen or a pharmaceutically acceptable salt thereof; and</li> <li id="ul0002-0006" num="0000">Y is selected from the group consisting of</li> </ul> </li> </ul> </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="23.11mm" wi="61.55mm" file="US20180000849A1-20180104-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I.</p> <p id="p-0005" num="0000"><chemistry id="CHEM-US-00003" num="00003"> <img id="EMI-C00003" he="36.32mm" wi="69.85mm" file="US20180000849A1-20180104-C00003.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0003" list-style="none"> <li id="ul0003-0001" num="0000"> <ul id="ul0004" list-style="none"> <li id="ul0004-0001" num="0000">wherein:</li> <li id="ul0004-0002" num="0000">L and M are independently selected from the group consisting of C<sub>1</sub>-C<sub>6 </sub>alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.</li> </ul> </li> </ul> </p>
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4'-SUBSTITUTED NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present invention is directed to 4′-substituted nucleoside derivatives of Formula I</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="18.29mm" wi="52.66mm" file="US20180002366A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and their use in the inhibition of HIV reverse transcriptase, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS and/or ARC.</p>
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3-ALKYL PYRIDINIUM COMPOUND FROM RED SEA SPONGE WITH POTENT ANTIVIRAL ACTIVITY (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">Method for treating a viral infection in a patient, comprising administering to the patient a therapeutically effective amount of a compound, or a pharmaceutically acceptable salt thereof, comprising a moiety represented by figure (I), wherein R<sub>1 </sub>is a saturated or unsaturated bivalent hydrocarbon group. Viruses subject to treatment can include HIV and flaviviruses such as west nile, dengue, or hepatitis C virus. Compositions and methods of isolation and purification are also described including from the Red Sea sponge.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.43mm" wi="51.22mm" file="US20180000799A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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S-TRIAZOLYL ALPHA-MERCAPTO ACETANILIDES AS INHIBITORS OF HIV REVERSE TRANSCRIPTASE (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">A series of S-triazolyl α-mercaptoacetanilides having general structure (1) are provided, where Q is CO<sub>2</sub>H, CONR<sub>2</sub>, SO<sub>3</sub>H, or SO<sub>2</sub>NR<sub>2</sub>. The compounds inhibit several variants of the reverse transcriptase of HIV, and are useful in the treatment of HIV infections.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="28.96mm" wi="68.16mm" file="US20180002296A1-20180104-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOSITIONS AND METHODS FOR REACTIVATING LATENT IMMUNODEFICIENCY VIRUS (Fri, 05 Jan 2018)
<p id="p-0001" num="0000">The present disclosure provides compositions and methods for reactivating latent immunodeficiency virus and/or reducing transcription of HIV integrated into the genome of an HIV-infected cell. The present disclosure provides compositions and methods for treating an immunodeficiency virus infection.</p>
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TRITERPENOID INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 05 Jan 2018)
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, triterpenoid compounds that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula (I). These compounds are useful for the treatment of HIV and AIDS.
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AZA-SUBSTITUTED INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 05 Jan 2018)
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, aza-substituted triterpenoid compounds that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula (I). These compounds are useful for the treatment of HIV and AIDS.
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AZADECALIN DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 05 Jan 2018)
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, azadecaline derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula (I). These compounds are useful for the treatment of HIV and AIDS.
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ANTIBODY-DRUG CONJUGATES AND THERAPEUTIC METHODS USING THE SAME (Fri, 05 Jan 2018)
The invention discloses an antibody-drug conjugate of Formula (I): (I) Ab-[L-Dn]x wherein: Ab comprises a broadly neutralizing anti-HIV antibody; L comprises a linker molecule covalently bonded to said broadly neutralizing anti-HIV antibody; D comprises one or more drugs comprising an HIV therapeutic compound covalently bonded to said linker molecule L, wherein said one or more broadly neutralizing anti-HIV antibodies Ab specifically bind to an HIV envelope glycoprotein and said one or more drugs D specifically bind to an HIV envelope glycoprotein; n is selected from 1-4; and x is selected from 1-12.
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DERIVATIVES OF BETULIN (Thu, 04 Jan 2018)
The present invention relates to compounds characterized by having a structure according to the following Formula I: , or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.35mm" wi="69.85mm" file="US20170369509A1-20171228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">(wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">Z<sup>1 </sup>is NR<sup>4</sup>;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is hydrogen or lower alkyl;</li> <li id="ul0002-0003" num="0000">X is a single bond, a hetero atom group selected from O, S, SO, SO<sub>2 </sub>and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene;</li> <li id="ul0002-0004" num="0000">R<sup>2 </sup>is optionally substituted aryl;</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and</li> <li id="ul0002-0006" num="0000">R<sup>4 </sup>and Z<sup>2 </sup>part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.</li> </ul> </li> </ul> </p>
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2-PHENETHENYLTETRAHYDRO ISOQUINOLINES USEFUL AS ANTI-HIV COMPOUNDS (Fri, 29 Dec 2017)
<p id="p-0001" num="0000">This invention provides, among other things, tetrahydroisoquinolines useful for treating viral infections, pharmaceutical formulations containing such compounds, as well as methods of inhibiting the replication of a virus, such as HIV, or treating a disease, such as AIDS.</p>
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ACTIVATORS OF HIV LATENCY (Fri, 29 Dec 2017)
The present invention relates to novel compounds which active HIV expression in latently infected cells. More particularly, the invention relates to pharmaceutical compositions comprising the novel compounds and their use in activating HIV expression in latently infected cells. Further still, the invention relates to pharmaceutical compositions comprising the novel compounds in combination with anti-HIV therapy compounds and their use in treating HIV infection in both animals and humans. The invention further provides means for preparing the compounds.
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HUMAN IMMUNODEFICIENCY VIRUS (HIV) -NEUTRALIZING ANTIBODIES (Thu, 28 Dec 2017)
The invention provides a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies are characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also provided. Furthermore, methods for vaccination using suitable epitopes are provided.
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Spirocyclic Heterocycle Compounds Useful as HIV Integrase Inhibitors (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present invention relates to Spirocyclic Heterocycle Compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, B, X, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </sup>are as defined herein. The present invention also relates to compositions comprising at least one Spirocyclic Heterocycle Compound, and methods of using the Spirocyclic Heterocycle Compounds for treating or preventing HIV infection in a subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="31.50mm" wi="67.39mm" file="US20170362252A1-20171221-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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MODULATORS OF THE PROSTACYCLIN (PGI2) RECEPTOR USEFUL FOR THE TREATMENT OF DISORDERS RELATED THERETO (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: Pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease, a congenital heart disease, portal hypertension, HIV infection, ingestion of a drug or toxin, hereditary hemorrhagic telangiectasia, splenectomy, pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH); PAH with significant venous or capillary involvement; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack, angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).</p>
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COMPOSITION AND METHOD FOR AFFECTING CYTOKINES AND NF-KB (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present invention discloses a composition and method for effecting various cytokines and NF-κB by administering an effective amount of a phyto-percolate composition to an individual. In various exemplary embodiments, the composition is claimed to be useful for the effective treatment of inflammation, cancer, and/or various infections including HIV by regulation of various interleukins, such as IL-10 and IL-2, and of transcription factors including NF-κB.</p>
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METHODS FOR MODULAR SYNTHESIS OF N-GLYCANS AND ARRAYS THEREOF (Fri, 22 Dec 2017)
<p id="p-0001" num="0000">The present disclosure relates to novel modular methods for generating a diversity of N-glycans of high mannose, hybrid and complex types. The present disclosure also relates to exemplary arrays of the synthesized N-glycans spotted onto aluminium oxide coated slides. These arrays can be used to detect and analyze binding interactions between the synthesized N-glycans and glycan binding molecules, such as HIV-1 neutralizing antibodies. The present disclosure also relates to methods for identifying agents that bind to various types of molecules on the arrays and to defining the structural elements of the molecules on the arrays that bind to those agents. The arrays and methods provided herein may be used for general epitope identification, drug discovery and as analytical tools. The present disclosure also provides useful glycans and epitope determinants that are useful in detecting, diagnosing, recurrence monitoring and preventing pathological diseases such as HIV.</p>
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SYNTHESIS OF CARBAMOIL-PYRIDONE INHIBITORS OF HIV INTEGRASE AND INTERMEDIATE COMPOUNDS (Wed, 20 Dec 2017)
FIELD: pharmacology. SUBSTANCE: invention relates to new crystalline forms of sodium salt or sodium salt monohydrate of a compound of the general formula (AA). The compound has inhibitory activity against HIV integrase. The AA compound corresponds to the following structural formula: . The crystalline form of the sodium salt of the AA compound has (a) characteristic diffraction peaks at 2-theta angles of 6.4±0.2°; 9.2±0.2°; 13.8°±0.2°; 19.2±0.2° and 21.8°±0.2°, in the X-ray powder diffraction pattern and/or (b) the characteristic infrared absorption spectra at 1641 cm-1 ± 2 cm-1, 1536 cm-1 ± 2 cm-1, 1503 cm-1 ± 2 cm-1 and 1424 cm-1 ± 2 cm-1 and/or (c) 13C-NMR spectra in the solid state, substantially as shown in Fig. 3. The crystalline form of the sodium salt monohydrate of the AA compound has (d) characteristic diffraction peaks at 2-theta angles equal to 8.0°±0.2°; 9.3°±0.2°; 11.3°±0.2°; 16.0°±0.2° and 22.8°±0.2°, in the X-ray powder diffraction pattern and/or (e) characteristic infrared absorption spectra at 1637 cm-1 ± 2 cm-1, 1536 cm-1 ± 2 cm-1, 1501 cm-1 ± 2 cm-1 and 1422 cm-1 ± 2 cm-1 and has substantially X-ray diffraction patterns, as shown in Fig. 4. The invention also relates to a pharmaceutical composition comprising the said crystalline forms, as well as to a process for preparation of the crystalline form of the sodium salt monohydrate of the AA compound. The method includes stages: a) dissolution of the sodium salt compounds of the formula (AA) in a solution of THF (tetrahydrofuran)-water, b) addition of aqueous NaOH to the obtained solution, c) stirring of the obtained mixture, d) filtering of the obtained sediment, washing it with a THF solution - water and THF and drying. EFFECT: crystalline forms of the sodium salt and its monohydrate show high solubility in water or saline, have high bioavailability, increased stability to heat and light, and simplify compound application. 13 cl, 7 dwg, 3 ex
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3-(6-alkoxy-5-chlorobenzo[d]isoxazol-3-yl)propanoic acid useful as kynurenine monooxygenase inhibitors (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">Compound of formula (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.37mm" wi="58.42mm" file="US09932328-20180403-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is heteroaryl either unsubstituted or substituted by methyl, ethyl, halo or ═O; and</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is H, methyl or ethyl; <br/> and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, acute kidney disease, acute kidney injury, other conditions associated with systemic inflammatory response syndrome (SIRS), Huntington's disease, Alzheimer's disease, spinocerebellar ataxias, Parkinson's disease, AIDS-dementia complex, HIV infection, amylotrophic lateral sclerosis (ALS), depression, schizophrenia, sepsis, cardiovascular shock, severe trauma, acute lung injury, acute respiratory distress syndrome, acute cholecystitis, severe burns, pneumonia, extensive surgical procedures, ischemic bowel, severe acute hepatic disease, severe acute hepatic encephalopathy or acute renal failure. </li> </ul> </li> </ul> </p>
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DERIVATIVES OF BETULIN (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">The present invention relates to compounds characterized by having a structure according to the following Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.20mm" wi="69.85mm" file="US20170348324A1-20171207-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">, or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.</p>
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COMPETITIVE INHIBITORS OF INVARIANT CHAIN EXPRESSION AND/OR ECTOPIC CLIP BINDING (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">The invention relates to methods for modulating the immune function through targeting of CLIP molecules. The result is wide range of new therapeutic regimens for treating, inhibiting the development of, or otherwise dealing with, a multitude of illnesses and conditions, including autoimmune disease, cancer, Alzheimer's disease, allergic disease, transplant and cell graft rejection, HIV infection and other viral, bacterial, and parasitic infection, and AIDS. Methods are also provided for preparing a peptide having the property of being able to displace CLIP by feeding one or more peptide sequences into software that predicts MHC Class II binding regions in an antigen sequence and related products.</p>
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SMALL MOLECULE INHIBITORS OF VIRAL PROTEIN INTERACTIONS WITH HUMAN T-RNA (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">Disclosed herein are compounds, compositions and methods of their use to treat HIV/AIDS disease in a subject in need thereof, wherein the compositions comprise small molecule inhibitors that inhibit viral preparation or viral recruitment of human tRNA<sub>3</sub><sup>Lys</sup>.</p>
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NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (Fri, 08 Dec 2017)
<p id="p-0001" num="0000">Compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="36.49mm" wi="55.46mm" file="US20170349585A1-20171207-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">are HIV reverse transcriptase inhibitors, wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>E</sup>, L, M and Z are defined herein. The compounds of Formula I and their pharmaceutically acceptable salts are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.</p>
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Human immunodeficiency virus (HIV) -neutralizing antibodies (Fri, 08 Dec 2017)

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POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR USE FOR THE TREATMENT OF HIV INFECTIONS (Thu, 07 Dec 2017)
Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein R 1 , X, Y 1 , Y 2 , or L are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
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POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR USE FOR THE TREATMENT OF HIV INFECTIONS (Thu, 07 Dec 2017)
Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): including stereoisomers and pharmaceutically acceptable salts thereof, wherein L, R 1 , R 5 , W, X, Y 1 , Y 2 , and Z are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
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HIV 인테그라제 억제제로서 유용한 치환된 퀴놀리진 유도체 (Wed, 06 Dec 2017)
본 발명은 하기 화학식 I의 치환된 퀴놀리진 유도체 및 그의 제약상 허용되는 염 또는 전구약물에 관한 것이다. 본 발명은 또한 적어도 1종의 치환된 퀴놀리진 유도체를 포함하는 조성물, 및 대상체에서 HIV 감염을 치료하거나 또는 예방하기 위해 치환된 퀴놀리진 유도체를 사용하는 방법에 관한 것이다. <화학식 I> 상기 식에서, X, Y, R, R, R,R, R, R 및 R은 본원에 정의된 바와 같다. JPEG pat00086.jpg 44 75 1 2 3 4 5 9 10
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신규 3-인돌 치환 유도체, 제약 조성물 및 사용 방법 (Sat, 02 Dec 2017)
화학식 I의 화합물 또는 그의 제약상 허용되는 거울상이성질체, 염 또는 용매화물이 제공된다. <화학식 I> 본 발명은 또한 TDO2 억제제로서의 화학식 I의 화합물의 용도에 관한 것이다. 본 발명은 또한 암, 신경변성 장애 예컨대 파킨슨병, 알츠하이머병 및 헌팅톤병, 만성 바이러스 감염 예컨대 HCV 및 HIV, 우울증, 및 비만의 치료 및/또는 예방을 위한, 화학식 I의 화합물의 용도에 관한 것이다. 본 발명은 또한 화학식 I의 화합물의 제조 방법에 관한 것이다. TIFF pct00212.tif 81 74
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바이러스 감염의 치료 및 예방의 용도를 위한 신규한 퀴놀린 유도체 (Tue, 28 Nov 2017)
본 발명은 화학식 (1)의 퀴놀린 유도체 또는 이의 약학적으로 허용 가능한 염들 중 하나에 관한 것이다. (1) 본 발명은 더욱이 약제로서의 용도 및 바이러스 또는 레트로바이러스 감염 및 특히 AIDS 또는 AIDS-관련 상태 또는 인간 면역 결핍 바이러스(HIV)의 치료 또는 예방에서의 용도를 위한 상기 퀴놀린 유도체에 관한 것이다. 본 발명은 또한 상기 퀴놀린 유도체를 포함하는 약학 조성물 및 신규한 중간체 화합물에 관해 이것을 제조하는 과정에 관한 것이다. JPEG pct00014.jpg 52 70
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烟草所含的异黄酮类化合物及其制备方法和应用 (Sat, 25 Nov 2017)
本发明公开了一种如式(Ⅰ)所示烟草所含的异黄酮类化合物及其制备方法和应用,式(Ⅰ)。将烟草样品粉碎后以70%的丙酮超声提取3次,合并提取液,过滤,减压浓缩滤液至提取液的1/4~1/6体积,静置后滤除沉淀物,然后用乙酸乙酯萃取3次,获得乙酸乙酯部分萃取液;将萃取液浓缩成浸膏,浸膏用硅胶柱层析初分,然后采用高效液相制备色谱进一步分离,即得到所需的异黄酮类化合物。对该化合物进行了抗抗氧化活性和抗HIV-1活性筛选,实验结果显示化合物显示出较强的抗氧化和抗HIV‑1活性。
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LIM KINASE INHIBITORS (Fri, 24 Nov 2017)
A dynamic actin cytoskeleton is necessary for viral entry, intracellular migration, and virion release. For the human immunodeficiency virus (HIV), during viral entry, the virus triggers early actin activity through hijacking chemokine coreceptor signaling, which activates a viral dependency host factor cofilin and its kinase, the LIM domain kinase (LIMK).. Although knockdown of human LIMK1 with siRNA inhibits HIV infection, no specific small molecule inhibitor of LIMK is available. Here we describe the design and development of novel classes of small molecule inhibitors of human LIMK, based on different molecular scaffolds, for inhibiting infection by HIV, Ebola, and other viruses. Compounds of the invention can also be used for treatment of sexually transmitted diseases such as Herpes and Chlamydia.
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RETROVIRAL CAPSID CRYSTAL STRUCTURE AND USE THEREOF (Fri, 24 Nov 2017)
This invention relates to computer-based methods for identifying compounds that inhibit nucleotide recruitment activity of a retrovirus capsid, such as HIV-1. The atomic structure of a hexamer assembled from retrovirus capsid proteins is provided which includes at least two side-chain atoms from at least two Arg-18 monomer residues. Molecular structures may then be fitted to at least one side-chain atom of at least one of the Arg-18 residues. Other computer-based methods may comprise providing the atomic structure of a retrovirus capsid hexamer and fitting a molecular structure to at least one residue of it. The atomic structure may then be manipulated to determine if the molecular structure induces changes in the retrovirus capsid hexamer structure which result in closure of its nucleotide recruitment pore or its rearrangement into a conformation that reduces nucleotide binding, or stabilizes such a conformation. This may be useful in the development of anti-retroviral therapies.
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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 17 Nov 2017)
Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS. (I)
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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 17 Nov 2017)
Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS. (I)
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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 17 Nov 2017)
Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS. (I)
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HIV replication inhibiting pyrimidines (Fri, 10 Nov 2017)
<p id="p-0001" num="0000">This invention concerns HIV replication inhibitors of formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.38mm" wi="69.85mm" file="US09981919-20180529-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, wherein the ring containing -a<sup>1</sup>=a<sup>2</sup>-a<sup>3</sup>=a<sup>4</sup>- and -b<sup>1</sup>=b<sup>2</sup>-b<sup>3</sup>=b<sup>4</sup>- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl; n is 0 to 5; m is 1 to 4; R<sup>1 </sup>is hydrogen; aryl; formyl; C<sub>1-6</sub>alkylcarbonyl; C<sub>1-6</sub>alkyl; C<sub>1-6</sub>alkyloxycarbonyl; substituted C<sub>1-6</sub>alkyl, C<sub>1-6</sub>alkylcarbonyl, C<sub>1-6</sub>alkyloxycarbonyl, C<sub>1-6</sub>alkylcarbonyloxy; substituted C<sub>1-6</sub>alkyloxyC<sub>1-6</sub>alkylcarbonyl; R<sup>2 </sup>is hydroxy, halo, optionally substituted C<sub>1-6</sub>alkyl, C<sub>3-7</sub>cycloalkyl, optionally substituted C<sub>2-6</sub>alkenyl, optionally substituted C<sub>2-6</sub>alkynyl, C<sub>1-6</sub>alkyloxy, C<sub>1-6</sub>alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C<sub>1-6</sub>alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)<sub>p</sub>R<sup>6</sup>, —NH—S(═O)<sub>p</sub>R<sup>6</sup>, —C(═O)R<sup>6</sup>, —NHC(═O)H, —C(═O)NHNH<sub>2</sub>, —NHC(═O)R<sup>6</sup>, —C(═NH)R<sup>6 </sup>or a 5-membered heterocycle; X<sub>1 </sub>is —NR<sup>5</sup>—, —NH—NH—, —N═N—, —O—, —C(═O)—, C<sub>1-4</sub>alkanediyl, —CHOH—, —S—, —S(═O)<sub>p</sub>—, —X<sub>2</sub>—C<sub>1-4</sub>alkanediyl- or —C<sub>1-4</sub>alkanediyl-X<sub>2</sub>—; R<sup>3 </sup>is NHR<sup>13</sup>; NR<sup>13</sup>R<sup>14</sup>; —C(═O)—NHR<sup>13</sup>; —C(═O)—NR<sup>13</sup>R<sup>14</sup>; —C(═O)—R<sup>15</sup>; —CH═N—NH—C(═O)—R<sup>16</sup>; substituted C<sub>1-6</sub>alkyl; optionally substituted C<sub>1-6</sub>alkyloxyC<sub>1-6</sub>alkyl; substituted C<sub>2-6</sub>alkenyl; substituted C<sub>2-6</sub>alkynyl; C<sub>1-6</sub>alkyl substituted with hydroxy and a second substituent; —C(═N—O—R<sup>8</sup>)—C<sub>1-4</sub>alkyl; R<sup>7</sup>; or —X<sub>3</sub>—R<sup>7</sup>; R<sup>4 </sup>is halo, hydroxy, C<sub>1-6</sub>alkyl, C<sub>3-7</sub>cycloalkyl, C<sub>1-6</sub>alkyloxy, cyano, nitro, polyhaloC<sub>1-6</sub>alkyl, polyhaloC<sub>1-6</sub>alkyloxy, aminocarbonyl, C<sub>1-6</sub>alkyloxycarbonyl, C<sub>1-6</sub>alkylcarbonyl, formyl, amino, mono- or di(C<sub>1-4</sub>alkyl)amino; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them. </p>
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ANTIVIRAL JAK INHIBITORS USEFUL IN TREATING OR PREVENTING RETROVIRAL AND OTHER VIRAL INFECTIONS (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">Compounds, compositions, and methods of treatment and prevention of HIV infection are disclosed. The compounds are pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidine JAK inhibitors. Combinations of these JAK inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, and the like, are also disclosed. In one embodiment, the combinations include a combination of adenine, cytosine, thymidine, and guanine nucleoside antiviral agents, optionally in further combination with at least one additional antiviral agent that works via a different mechanism than a nucleoside analog. This combination has the potential to eliminate the presence of HIV in an infected patient.</p>
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MUTAGENIC NUCLEOSIDE ANALOGS AND USES THEREOF (Fri, 03 Nov 2017)
<p id="p-0001" num="0000">The present disclosure provides nucleoside analogs of Formula (I) or (II). The nucleoside analogs are expected to show multiple tautomerism and may increase the mutation of an RNA and/or DNA (be mutagenic) of a virus or cancer cell. The multiple tautomerism and mutagenesis of the nucleoside analogs may be adjusted by substituting the nucleoside analogs with one or more electron-donating groups and/or electron-withdrawing groups to increase or decrease the pK<sub>a </sub>(e.g., to a pK<sub>a </sub>between 5.5 or 8.5). The present disclosure also provides pharmaceutical compositions and kits including the nucleoside analogs and methods of treating a viral infection (e.g., influenza, HIV infection, or hepatitis) or cancer using the nucleoside analogs, pharmaceutical compositions, or kits.</p>
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MOFEZOLAC DERIVATIVES AS MULTI-FUNCTIONS SELECTIVE COX-1 INHIBITORS (Fri, 03 Nov 2017)
The invention relates to a new class of compounds of formula (I) targeting COX-1. The invention also relates to the use of some of such compounds as a tool to investigate the structure and function of the enzyme, in the treatment targeting COX-1 or detection of COX-1 in relating disorders or diseases such as cancer and neuroinflammation, in particular in neurological (e.g. autism spectrum disorders) and neurodegenerative diseases (e.g. Alzheimer's diseases, Parkinson's diseases, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), traumatic brain injury (TBI), HIV dementia and prion diseases), and in gynecological tumour (e.g. ovarian cancer), neck and head tumor, and haematological tumours (e.g. multiple myeloma) and in the detection of COX-1 in "in vitro" (cells and tissues) and in "in vivo".
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Fused tricyclic heterocyclic compounds as HIV integrase inhibitors (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">The present invention relates to Fused Tricyclic Heterocycle Derivatives of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, X, Y, m, R1, R5, Ra and Rb are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocycle Derivative, and methods of using the Fused Tricyclic Heterocycle Derivatives for treating or preventing HIV infection in a subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="58.00mm" file="US09951079-20180424-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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C17-ARYL SUBSTITUTED BETULINIC ACID ANALOGS (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.02mm" wi="71.46mm" file="US20170305962A1-20171026-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">These compounds are useful for the treatment of HIV and AIDS.</p>
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COMPOSITIONS AND METHODS FOR TREATING VIRAL INFECTIONS (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">The present invention provides compositions methods for treating susceptible viral infections, especially hepatitis C viral (HCV) infections as well as co infections of HCV with other viruses such as HBV and/or HIV. In one embodiment, the present invention provides compositions having the formula (I) and their use in treating viral infections:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.19mm" wi="72.73mm" file="US20170304344A1-20171026-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">or a pharmaceutically acceptable salt, ester, stereoisomer, tautomers, solvate, prodrug, or combination thereof.</li> </ul> </li> </ul> </p>
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COMPOUNDS FOR INHIBITING DRUG-RESISTANT STRAINS OF HIV-1 INTEGRASE (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">A method of inhibiting drug-resistant HIV-1 integrase in a subject comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt or ester thereof, having a structure of:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.89mm" wi="61.72mm" file="US20170305904A1-20171026-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X is N, C(OH), or CH; <br/> Y is H or OH; <br/> each of Z<sup>1</sup>-Z<sup>5 </sup>is independently H or halogen; <br/> R<sup>4 </sup>is H, OH, NH<sub>2</sub>, NHR<sup>8</sup>, NR<sup>8</sup>R<sup>9 </sup>or R<sup>8</sup>; <br/> R<sup>5</sup>, R<sup>6</sup>, and R<sup>7 </sup>is each independently H, halogen, OR<sup>8</sup>, R<sup>8</sup>, NHR<sup>8</sup>, NR<sup>8</sup>R<sup>9</sup>, CO<sub>2</sub>R<sup>8</sup>, CONR<sup>8</sup>R<sup>9</sup>, SO<sub>2</sub>NR<sup>8</sup>R<sup>9</sup>, or R<sup>5 </sup>and R<sup>6 </sup>together with the carbon atoms to which R<sup>5 </sup>and R<sup>6 </sup>are attached form an optionally-substituted carbocycle or optionally-substituted heterocycle; and <br/> R<sup>8 </sup>and R<sup>9 </sup>is each independently H, optionally-substituted alkyl, optionally-substituted alkenyl, optionally-substituted alkynyl, optionally-substituted aryl, optionally-substituted cycloalkyl, optionally-substituted cycloalkylene, optionally-substituted heterocycle, optionally-substituted amide, optionally-substituted ester, or R<sup>8 </sup>and R<sup>9 </sup>together with the nitrogen to which R<sup>8 </sup>and R<sup>9 </sup>are attached form an optionally-substituted heterocycle. </p>
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Inhibitors of human immunodeficiency virus replication (Fri, 27 Oct 2017)
<p id="p-0001" num="0000">Compounds of Formula I, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.85mm" wi="53.42mm" file="US09855230-20180102-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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COMPOUNDS FOR THE TREATMENT OF HIV (Thu, 26 Oct 2017)
The invention relates to a compound of Formula II: a pharmaceutically-acceptable salt, hydrate, solvate, tautomer, optical isomer, E-isomer, Z-isomer, or combination thereof; X is selected from Se, N-OH, NH, NO 2 , CN, N-CN, N=O, O or S, and the remaining substituents are described herein; and a composition thereof. The invention also relates to a method of administration thereof; and use thereof to treat HIV.
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4'-substituted nucleoside-derivatives as HIV reverse transcriptase inhibitors (Fri, 29 Sep 2017)
The present invention is directed to 4-substituted nucleoside derivatives of Formula I (Formula I), and their use in the inhibition of HIV reverse transcriptase, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS and/or ARC.
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A PREPARATION METHOD OF DIASTEREOMERICALLY PURE TENOFOVIR ALAFENAMIDE OR ITS SALTS (Fri, 22 Sep 2017)
The invention relates to an efficient preparation method of diastereomerically pure Tenofovir Alafenamide (TA) of structure la with the absolute configuration (S) at the phosphorus atom - Sp-diastereoisomer. Tenofovir Alafenamide Fumarate of formula 2 (TAF) is a reverse transcriptase inhibitor, which is currently in the clinical study stage as a prodrug of Tenofovir 3 for the treatment of HIV infection and hepatitis B. Compared to the hitherto used prodrug, Tenofovir disoproxil fumarate of formula 4, TAF exhibits greater antiviral activity and better distribution in the lymphatic system.
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一类N-烷基吲哚类化合物在制备抗HIV药物中的用途 (Wed, 20 Sep 2017)
本发明公开了一类如通式(I)所示的吲哚类化合物,以及其药学上可接受的盐在制备抗HIV药物或保健品中的应用;并公开了该类化合物的制备方法、以及含有该类化合物的药物组合物在制备抗HIV药物或保健品中的应用。
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 15 Sep 2017)
<p id="p-0001" num="0000">The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="60.45mm" file="US20170260203A1-20170914-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">(wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">Z<sup>1 </sup>is NR<sup>4</sup>;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is hydrogen or lower alkyl;</li> <li id="ul0002-0003" num="0000">X is a single bond, a hetero atom group selected from O, S, SO, SO<sub>2 </sub>and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene;</li> <li id="ul0002-0004" num="0000">R<sup>2 </sup>is optionally substituted aryl;</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and</li> <li id="ul0002-0006" num="0000">R<sup>4 </sup>and Z<sup>2 </sup>part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.</li> </ul> </li> </ul> </p>
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POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE (Fri, 15 Sep 2017)
<p id="p-0001" num="0000">Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="65.28mm" file="US20170260204A1-20170914-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">including stereoisomers and pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>, X, W, Y<sup>1</sup>, Y<sup>2</sup>, Z<sup>1</sup>, and Z<sup>4 </sup>are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.</p>
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METHODS FOR MODULAR SYNTHESIS OF N-GLYCANS AND ARRAYS THEREOF (Fri, 15 Sep 2017)
The present disclosure relates to novel modular methods for generating a diversity of N-glycans of high mannose, hybrid and complex types. The present disclosure also relates to exemplary arrays of the synthesized N-glycans spotted onto aluminium oxide coated slides. These arrays can be used to detect and analyze binding interactions between the synthesized N-glycansand glycan binding molecules, such as HIV-1 neutralizing antibodies. The present disclosure also relates to methods for identifying agents that bind to various types of molecules on the arrays and to defining the structural elements of the molecules on the arrays that bind to those agents. The arrays and methods provided herein may be used for general epitope identification, drug discovery and as analytical tools. The present disclosure also provides useful glycans and epitope determinants that are useful in detecting, diagnosing, recurrence monitoring and preventing pathological diseases such as HIV.
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ACYCLIC ANTIVIRALS (Fri, 15 Sep 2017)
Disclosed herein are nucleotide analogs, methods of synthesizing nucleotide analogs and methods of treating diseases and/or conditions such as a HBV and/or HDV and/or HIV infection with one or more nucleotide analogs
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5-SULFAMOYL-2-HYDROXYBENZAMIDE DERIVATIVES (Fri, 15 Sep 2017)
The invention is directed to substituted salicylamide derivatives. Specifically, the invention is directed to compounds according to Formula (I): wherein R, R1 and R2 are as defined herein, or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of CD73 and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with CD73 inhibition, such as AIDS, the treatment of HIV, autoimmune diseases, infections, atherosclerosis, and ischemia–reperfusion injury. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting CD73 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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一种分离自蓝花黄芩的新型克罗烷型二萜类化合物及其在制备抗HIV药物中的用途 (Sat, 09 Sep 2017)
本发明属于植物化学技术领域,具体涉及一种分离自蓝花黄芩的新型克罗烷型二萜类化合物及其在制备抗HIV药物中的用途。所述新克罗烷型二萜类化合物具有式I所示的结构:其中R1选自Ac、Bz,R2选自OH、OAc或OBz,R3选自H、OAc或OBz。本发明式I化合物可用于治疗和/或预防由HIV‑1感染引起的疾病。
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USE OF 2-OXO-2H-PYRROL-1(5H)-CARBOXAMIDE DERIVATIVES AS ANTI-HIV AGENTS AND PROCESS FOR THE PRODUCTION THEREOF (Sat, 09 Sep 2017)
The present invention relates to the use in the medical field of 2-oxo-2H-pyrrol- 1 (5)-carboxamide derivatives in the treatment of HIV infections, pharmaceutical compositions containing these derivatives as active ingredients, and a process for the preparation of such derivatives.
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C-3 NOVEL TRITERPENE WITH C-17 AMINE DERIVATIVES AS HIV INHIBITORS (Sat, 09 Sep 2017)
The present invention relates to to C-3 novel triterpene with C-17 amine derivatives of formula (I); or pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, R4, R5 and 'n' are as defined herein. The present invention also relates to pharmaceutical compositions comprising compounds of formula (I) and process for preparing them, and their use for the treatment of viral diseases and particularly HIV mediated diseases.
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SWARM IMMUNIZATION WITH ENVELOPES FROM CH505 (Sat, 09 Sep 2017)
In certain aspects the invention provides HIV-1 immunogens, including CH505 HIV-1 envelopes and selections therefrom, and methods for swarm immunizations using combinations of HIV-1 envelopes.
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COMPOUNDS AND COMPOSITIONS FOR TREATING HIV WITH DERIVATIVES OF BETULIN (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention relates to compounds characterized by having a structure according to the following Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="46.57mm" wi="75.78mm" file="US20170252356A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.</p>
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LONG-ACTING HIV PROTEASE INHIBITOR (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention provides useful compounds for HIV protease inhibitor. A compound represented by the following formula or its pharmaceutically acceptable salt:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.25mm" wi="63.50mm" file="US20170253607A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein ring A is</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="70.53mm" wi="67.82mm" file="US20170253607A1-20170907-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">R<sup>4 </sup>is —Y—Z, hydrogen atom, halogen, hydroxy and the like,</li> <li id="ul0002-0002" num="0000">R<sup>5 </sup>is hydrogen atom, halogen, hydroxy and the like,</li> <li id="ul0002-0003" num="0000">R<sup>6 </sup>is each independently halogen, hydroxy, carboxy and the like,</li> <li id="ul0002-0004" num="0000">ring A may be substituted with said R<sup>6 </sup>at any substitutable position(s),</li> <li id="ul0002-0005" num="0000">a is an integer of 0 to 7,</li> <li id="ul0002-0006" num="0000">ring B is substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted aromatic heterocyclyl,</li> <li id="ul0002-0007" num="0000">ring C is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl,</li> <li id="ul0002-0008" num="0000">R<sup>1 </sup>is —Y—Z, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl and the like,</li> <li id="ul0002-0009" num="0000">R<sup>2 </sup>and R<sup>3 </sup>are each independently —Y—Z or hydrogen atom,</li> <li id="ul0002-0010" num="0000">provided that at least one of R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>4 </sup>is a group represented by formula: —Y—Z,</li> <li id="ul0002-0011" num="0000">Y is a bond, or a spacer of any combination selected from the group consisting of —O—, —S—, —NR<sup>7</sup>—, —C(═O)—, —SO—, —SO<sub>2</sub>—, —NR<sup>7</sup>—C(═O)—, —C(═O)—NR<sup>7</sup>—, —NR<sup>7</sup>—C(═O)—NR<sup>7</sup>—, —O—C(═O)—NR<sup>7</sup>—, —NR<sup>7</sup>—C(═O)—O—, —SO<sub>2</sub>—NR<sup>7</sup>—, —NR<sup>7</sup>—SO<sub>2</sub>—, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene, substituted or unsubstituted aromatic carbocyclediyl, substituted or unsubstituted non-aromatic carbocyclediyl, substituted or unsubstituted aromatic heterocyclediyl and substituted or unsubstituted non-aromatic heterocyclediyl,</li> <li id="ul0002-0012" num="0000">R<sup>7 </sup>are each independently hydrogen atom, hydroxy, carboxy and the like, and</li> <li id="ul0002-0013" num="0000">Z is substituted aromatic carbocyclyl, substituted non-aromatic carbocyclyl, substituted aromatic heterocyclyl or substituted non-aromatic heterocyclyl.</li> </ul> </li> </ul> </p>
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 08 Sep 2017)
<p id="p-0001" num="0000">The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="69.85mm" file="US20170253616A1-20170907-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">(wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">Z<sup>1 </sup>is NR<sup>4</sup>;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is hydrogen or lower alkyl;</li> <li id="ul0002-0003" num="0000">X is a single bond, a hetero atom group selected from O, S, SO, SO<sub>2 </sub>and NH, or lower alkylane or lower alkenylene in which the hetero atom group may intervene;</li> <li id="ul0002-0004" num="0000">R<sup>2 </sup>is optionally substituted aryl;</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and</li> <li id="ul0002-0006" num="0000">R<sup>4 </sup>and Z<sup>2 </sup>part taken together forms a ring, to form a polycyclic compound; including e.g., a tricyclic or tetracyclic compound.</li> </ul> </li> </ul> </p>
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SYNTHESIS OF CARBAMOYLPYRIDONE HIV INTEGRASE INHIBITORS AND INTERMEDIATES (Thu, 31 Aug 2017)
A synthesis approach providing an early ring attachment via a bromination to compound I-I yielding compound II-II: whereby a final product such as AA: can be synthesized. In particular, the 2,4-difluorophenyl-containing sidechain is attached before creation of the additional ring Q.
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用作犬尿氨酸单加氧酶抑制剂的3‑(6‑烷氧基‑5‑氯苯并[d]异噁唑‑3‑基)丙酸 (Wed, 30 Aug 2017)
式(I)化合物及其盐(其中:R1为杂芳基,其为未取代的或被甲基、乙基、卤素或=O取代;和R2为H、甲基或乙基)是KMO抑制剂且可用于治疗多种障碍,例如急性胰腺炎、慢性肾脏疾病、急性肾病、急性肾损伤、与全身炎症反应综合征(SIRS)有关的其他病症、亨廷顿病、阿尔茨海默病、脊髓小脑共济失调、帕金森病、艾滋病痴呆复合征、HIV感染、肌萎缩侧索硬化(ALS)、抑郁症、精神分裂症、败血症、心血管休克、严重创伤、急性肺损伤、急性呼吸窘迫综合征、急性胆囊炎、重度烧伤、肺炎、扩大外科手术、缺血性肠病、严重急性肝病、严重急性肝性脑病或急性肾功能衰竭。
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多环碳酰基吡啶酮化合物及其药物用途 (Wed, 30 Aug 2017)
公开了治疗人免疫缺陷病毒(HIV)感染的化合物。所述化合物具有下式(Ia),包括其立体异构体和药学可接受的盐,其中A’、R1、R2和R3如本文定义。还公开了与该化合物相关的治疗和使用方法,还公开了包含该化合物的药物组合物。
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从喙果皂帽花中提取的阿朴啡生物碱及提取方法 (Sat, 26 Aug 2017)
本发明公开了一种从喙果皂帽花中提取的阿朴啡生物碱及提取方法,所述阿朴啡生物碱是一个连有硝基的阿朴啡生物碱,是一种天然化合物。该化合物对HIV‑1型病毒具有较好的抑制活性。
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Compounds for the treatment of HIV (Fri, 25 Aug 2017)
The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating a Retroviridae viral infection including an infection caused by the HIV virus.
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Crystal form of dolutegravir sodium and preparation method of crystal form (Sat, 19 Aug 2017)
The invention relates to a new crystal form of dolutegravir sodium. Compared with a known crystal form of the dolutegravir sodium, the new crystal form disclosed by the invention has one or more beneficial properties, such as good stability in water, high dissolubility, difficult moisture absorption, good storage stability and good particle shapes. The invention also relates to a preparation method of the new crystal form of the dolutegravir sodium, a pharmaceutical composition of the new crystal form and application of the new crystal form in preparation of a medicine for treating and/or preventing HIV-1 infection.
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RECOMBINANT HIV-1 ENVELOPE PROTEINS AND THEIR USE (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">HIV-1 Env ectodomain trimers stabilized in a prefusion mature closed conformation and methods of their use and production are disclosed. In several embodiments, the HIV-1 Env ectodomain trimers and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject. In additional embodiments, the therapeutically effective amount of the HIV-1 Env ectodomain trimers can be administered to a subject in a method of treating or preventing HIV-1 infection.</p>
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PROCESS FOR THE PREPARATION OF AMINO ALCOHOL DERIVATIVES OR SALTS THEREOF (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to a process for the preparation of amino alcohol derivatives or salts thereof. In particular the present invention relates to process for the preparation of amino alcohol derivatives or salts thereof which may be used as intermediates in the preparation of HIV reverse transcriptase inhibitors, more preferably Carbovir and Abacavir.</p> <p id="p-0002" num="0000">The present invention more specifically relates to a process for the preparation of (1S,4R)-4-amino-2-cyclopentene-1-methanol of Formula IIIa.</p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="12.02mm" wi="62.82mm" file="US20170233329A1-20170817-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">The present invention also specifically relates to process for the preparation of Abacavir sulfate of Formula II using compound of Formula IIIa prepared according to the process of the present invention.</p> <p id="p-0005" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="45.64mm" wi="69.17mm" file="US20170233329A1-20170817-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Inhibitors of HIV-1 entry and methods of use thereof (Fri, 18 Aug 2017)
<p id="p-0001" num="0000">The disclosure provides compositions and methods for sensitizing primary HIV-1, including transmitted/founder viruses, to neutralization by monoclonal antibodies, e.g., those directed against CD4-induced (CD4i) epitopes and the V3 region. In certain embodiments, the disclosure relates to the use of small molecules as microbicides to inhibit HIV-1 infection directly and to sensitize primary HIV-1 to neutralization by readily elicited antibodies.</p>
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연장된 베툴린산 유사체 (Sat, 12 Aug 2017)
약물 및 생체-영향 특성을 갖는 화합물, 이들의 약학적 조성물 및 사용 방법이 제시된다. 특히, 독특한 항바이러스 활성을 갖는, 하기 화학식 I 및 II의 화합물로 나타낸 바와 같은 베툴린산 유도체는 HIV 성숙 억제제로서 제공된다: . 이들 화합물은 HIV 및 AIDS의 치료에 유용하다. TIFF pct00058.tif 109 76
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.35mm" wi="69.85mm" file="US20170224694A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">(wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">Z<sup>1 </sup>is NR<sup>4</sup>;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is hydrogen or lower alkyl;</li> <li id="ul0002-0003" num="0000">X is a single bond, a hetero atom group selected from O, S, SO, SO<sub>2 </sub>and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene;</li> <li id="ul0002-0004" num="0000">R<sup>2 </sup>is optionally substituted aryl;</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and</li> <li id="ul0002-0006" num="0000">R<sup>4 </sup>and Z<sup>2 </sup>part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.</li> </ul> </li> </ul> </p>
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="69.85mm" file="US20170224695A1-20170810-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">(wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">Z<sup>1 </sup>is NR<sup>4</sup>;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is hydrogen or lower alkyl;</li> <li id="ul0002-0003" num="0000">X′ is a single bond, a hetero atom group selected from O, S, SO, SO<sub>2 </sub>and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene;</li> <li id="ul0002-0004" num="0000">R<sup>2 </sup>is optionally substituted aryl;</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and</li> <li id="ul0002-0006" num="0000">R<sup>4 </sup>and Z<sup>2 </sup>part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.</li> </ul> </li> </ul> </p>
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PLATINUM-CATALYZED SILICONE DRUG DELIVERY DEVICES AND METHODS OF USE THEREOF (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention provides intravaginal drug delivery devices, such as intravaginal rings, comprising active pharmaceutical ingredients (APIs) having terminal alkene, alkyne or carbonyl functionalities. The devices of the invention exhibit increased recovery of the active pharmaceutical ingredient from platinum-catalyzed silicone polymers due to the optimization of drug particle size and cure conditions. The present invention also provides methods of preventing unintended pregnancy in a female human, methods of preventing unintended pregnancy in a female human and HIV infection in a female human, and methods of preparing intravaginal drug delivery devices.</p>
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Polycyclic pyridone derivative having integrase inhibitory activity (Fri, 11 Aug 2017)
<p id="p-0001" num="0000">The present invention relates to a novel compound having an antiviral effect, more specifically, a pyridone derivative having HIV integrase inhibitory activity, and a medicament containing the same, in particular, an anti-HIV agent. The compound of the present invention has integrase inhibitory activity and/or cell proliferation inhibitory activity against viruses, in particular, HIV and drug-resistant strains thereof. Thus, the compound is useful in preventing or treating various diseases, viral infections (for example, AIDS), and the like in which integrase participates.</p>
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HIV治療におけるアポトーシスタンパク質阻害剤(IAP)のアンタゴニストの使用 (Fri, 11 Aug 2017)
<p num=""> 本明細書には、ヒト免疫不全ウィルス(HIV)の処置における、アポトーシスタンパク質阻害剤(IPA)の活性を調節する化合物の、単独での或いは他の治療剤と組み合わせての使用が、提供される。<br/>【選択図】図1</p>
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C-3 AND C-17 MODIFIED TRITERPENOIDS AS HIV-1 INHIBITORS (Fri, 11 Aug 2017)
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula (I). These compounds are useful for the treatment of HIV and AIDS.
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Novel Hydrates Of Dolutegravir Sodium (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The invention relates to novel hydrates of dolutegravir sodium and to processes for their preparation. Furthermore, the invention relates to a novel crystalline form of dolutegravir sodium, which is a useful intermediate for the preparation of one of the novel hydrates. In addition, the invention relates to the use of the novel hydrates for the production of pharmaceutical compositions. Finally, the invention relates to pharmaceutical compositions comprising an effective amount of the novel hydrates, to oral dosage forms comprising said pharmaceutical compositions, to a process for preparing said oral dosage forms, and to the use of said pharmaceutical compositions or dosage forms in the treatment of retroviral infections such as HIV-1 infections.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.69mm" wi="71.54mm" file="US20170217987A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Phenyl and tertbutylacetic acid substituted pyridinones having anti-HIV effects (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">Compounds of Formula I are disclosed and methods of treating viral infections with compositions comprising such compounds.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.88mm" wi="69.85mm" file="US09802898-20171031-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HIV protease inhibitors (Fri, 04 Aug 2017)
<p id="p-0001" num="0000">The present invention is directed to 2,6-morpholine derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein Z<sup>1</sup>, Z<sup>2</sup>, V<sup>1</sup>, V<sup>2</sup>, V<sup>3</sup>, R<sup>6</sup>, R<sup>6A</sup>, and X are defined herein. The invention also relates to methods of using the 2,6-morpholine derivatives of the invention for the inhibition of HV protease, the inhibition of HV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.88mm" wi="67.99mm" file="US09994587-20180612-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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HIVを治療するためのトール様受容体の調節因子 (Fri, 04 Aug 2017)
<p num="">式(II)のものおよび薬学的に許容されるその塩を含む、HIV感染症を治療するのに有用なTLR7調節因子を含む、方法、使用、薬学的レジメン、医薬組成物、およびキットが提供される。一局面において、ヒトにおいて、HIV感染症を治療する方法が提供され、この方法は、a)ヒトの血液または血漿中で検出されたHIVレベルを、第1のレベルから第2のレベルへと低下させるのに十分な抗レトロウイルス併用療法レジメンの薬学的有効量を、それを必要とするヒトに投与するステップであって、上記第2のレベルが、上記第1のレベルにおける上記ヒトの血液または血漿中のHIV濃度よりも低い、上記ヒトの血液または血漿中のHIV濃度を含む、ステップと、b)TLR7調節化合物、または薬学的に許容されるその塩の薬学的有効量を上記ヒトに投与するステップとを含む。<br/><img id="000160" he="41" wi="55" file="2017521434.tif" img-format="tif" img-content="drawing"/></p>
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INGENOL ANALOGS, PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE THEREOF (Fri, 04 Aug 2017)
The invention relates to compounds of Formula (I), (II), (III) or (IV), salts thereof, pharmaceutical compositions thereof, as well as methods of treating, curing or preventing HIV in subjects.
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PROCESSES AND INTERMEDIATES FOR PREPARING ANTI-HIV AGENTS (Thu, 03 Aug 2017)
The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties.
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PHOSPHONATE ANALOGS OF HIV INHIBITOR COMPOUNDS (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The invention is related to phosphorus substituted anti-viral inhibitory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.</p>
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="69.93mm" file="US20170209454A1-20170727-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">(wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">Z<sup>1 </sup>is NR<sup>4</sup>;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is hydrogen or lower alkyl;</li> <li id="ul0002-0003" num="0000">X is a single bond, a hetero atom group selected from O, S, SO, SO<sub>2 </sub>and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene;</li> <li id="ul0002-0004" num="0000">R<sup>2 </sup>is optionally substituted aryl;</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and</li> <li id="ul0002-0006" num="0000">R<sup>4 </sup>and Z<sup>2 </sup>part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.</li> </ul> </li> </ul> </p>
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SUBSTITUTED N-ACETYL-L-CYSTEINE DERIVATIVES AND RELATED COMPOUNDS (Fri, 28 Jul 2017)
<p id="p-0001" num="0000">Novel substituted N-acetyl-L-cysteine (NAC) derivatives and related compounds and methods of using these compounds for the treatment of diseases and/or conditions, including but not limited to diseases and/or conditions of, or involving, the Central Nervous System (CNS), including schizophrenia adrenoleukodystrophy, mitochondrial diseases (e.g. Leigh syndrome, Alpers′ disease, and MELAS), Huntington's disease, trichotillomania, HIV-associated neurocognitive disorder, hypoxic-ischemic encephalopathy, drug craving, and drug addiction.</p>
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AMINE DERIVATIVES OF LUPANES WITH HIV MATURATION INHIBITORY ACTIVITY (Fri, 28 Jul 2017)
The present invention relates to compounds characterized by having a structure according to the following Formula I: (I) or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
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POLYCYCLIC PYRIDONE DERIVATIVE HAVING INTEGRASE-INHIBITING ACTIVITY (Thu, 27 Jul 2017)
The present invention relates to a novel compound having an antiviral effect, more specifically, a pyridone derivative having HIV integrase inhibitory activity, and a medicament containing the same, in particular, an anti-HIV agent. The compound of the present invention has integrase inhibitory activity and/or cell proliferation inhibitory activity against viruses, in particular, HIV and drug-resistant strains thereof. Thus, the compound is useful in preventing or treating various diseases, viral infections (for example, AIDS), and the like in which integrase participates.
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4-pyridinonetriazine derivatives as HIV integrase inhibitors (Wed, 26 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to 4-Pyridinonetriazine Derivatives of Formula (I); and pharmaceutically acceptable salts thereof, wherein A, X, Y, R<sup>1</sup>, R<sup>2</sup>, R<sup>3 </sup>and R<sup>5 </sup>are as defined herein. The present invention also relates to compositions comprising at least one 4-Pyridinonetriazine Derivative, and methods of using the 4-Pyridinonetriazine Derivatives for treating or preventing HIV infection in a subject.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="29.38mm" wi="67.39mm" file="US09714243-20170725-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Besifovir compound and preparation method and application thereof (Wed, 26 Jul 2017)
The present invention relates to a besifovir compound and a preparation method and application thereof, the structure of the besifovir compound is as shown in a formula II. The invention also relates to the preparation method of the besifovir compound, a pharmaceutical composition containing the besifovir compound and the application of the besifovir compound in preparation of drugs for prevention and / or treatment of viral infections, especially hepatitis B virus (HBV) and / or human immunodeficiency virus (HIV) infection.
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NOVEL 4,6-DISUBSTITUTED AMINOPYRIMIDINE DERIVATIVES HAVE ANTI-HIV ACTIVITY (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">Novel 4,6-disubstituted aminopyrimidine derivatives with the following structure (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="39.29mm" wi="46.74mm" file="US20170204084A1-20170720-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">have anti-HIV activity.</p>
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Betulinic acid derivatives with HIV maturation inhibitory activity (Fri, 21 Jul 2017)
<p id="p-0001" num="0000">Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, betulinic acid derivaties that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I, II and III:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="131.15mm" wi="70.02mm" file="US09920090-20180320-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> These compounds are useful for the treatment of HIV and AIDS. </p>
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COMPOUNDS INHIBITING NEF-CALNEXIN INTERACTION (Fri, 21 Jul 2017)
The invention relates to compounds and methods for restoring or preserving cholesterol efflux in a cell infected with Human Immunodeficiency Virus (HIV) by preventing or decreasing an interaction between Negative Regulatory Factor (Nef) protein and Calnexin protein, and methods for screening for such compounds.
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SUSTAINED HIV PROTEASE INHIBITOR (Thu, 20 Jul 2017)
The present invention provides useful compounds for HIV protease inhibitor. A compound represented by formula or its pharmaceutically acceptable salt Formula: wherein ring A is R 4 is -Y-Z, hydrogen atom, halogen, hydroxy and the like, R 5 is hydrogen atom, halogen, hydroxy and the like, R 6 is each independently halogen, hydroxy, carboxy and the like, ring A may be substituted with said R 6 at any substitutable position(s), a is an integer of 0 to 7, ring B is substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted aromatic heterocyclyl, ring C is substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, R 1 is -Y-Z, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl and the like, R 2 and R 3 are each independently -Y-Z or hydrogen atom, provided that at least one of R 1 , R 2 , R 3 and R 4 is a group represented by formula: -Y-Z, Y is a bond, or a spacer of any combination selected from the group consisting of -O-, -S-, -NR 7 -, -C(=O)-, -SO-, -SO 2 -, -NR 7 -C(=O)-, -C(=O)-NR 7 -, -NR 7 -C(=O)-NR 7 -, -NR 7 -C(=O)-O-, -SO 2 -NR 7 -, -NR 7 -SO 2 -, substituted or unsubstituted alkylene, substituted or unsubstituted alkenylene, substituted or unsubstituted alkynylene, substituted or unsubstituted aromatic carbocyclediyl, substituted or unsubstituted non-aromatic carbocyclediyl, substituted or unsubstituted aromatic heterocyclediyl and substituted or unsubstituted non-aromatic heterocyclediyl, R 7 are each independently hydrogen atom, hydroxy, carboxy and the like, and Z is substituted aromatic carbocyclyl, substituted non-aromatic carbocyclyl, substituted aromatic heterocyclyl or substituted non-aromatic heterocyclyl.
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Use of Inhibitor of Apoptosis Protein (IAP) Antagonists in HIV Therapy (Fri, 14 Jul 2017)
<p id="p-0001" num="0000">Provided herein is the use of compounds that modulate the activity of inhibitor of apoptosis proteins (1APs), alone or in combination with other therapeutic agents, in the treatment of human immunodeficiency virus (HIV). Described herein is the use of IAP antagonists in the treatment of human immunodeficiency virus (HIV) in a mammal, alone or in combination with other therapeutic agents used in HIV therapy. In one aspect, provided herein is a method of treating human immunodeficiency virus (HIV) in an individual in need thereof comprising administering a therapeutically effective amount of at least one inhibitor of apoptosis proteins (IAP) antagonist.</p>
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[1-3]-thiazine-fulleropyrrolo derivatives of C60 and C70 as HIV-inhibitor agents (Fri, 14 Jul 2017)
<p id="p-0001" num="0000">Certain embodiments useful as HIV-inhibitor agents are directed to fullerene derivatives tetrahydro-1H—C<sub>60</sub>-fulleropyrrolo[1,2-c][1,3]thiazine salts (Formula I) or tetrahydro-1H—C<sub>70</sub>-fulleropyrrolo[1,2-c][1,3]thiazine salts (Formula II), while further embodiments are directed to α, β, γ, and/or δ isomer of tetrahydro-1H—C<sub>70</sub>-fulleropyrrolo[1,2-c][1,3]thiazine salt.</p>
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Tricyclopyrazole derivatives (Wed, 12 Jul 2017)
<p id="p-0001" num="0000">Compounds which are tricyclopyrazole derivatives or pharmaceutically acceptable salts thereof, their preparation process and pharmaceutical compositions comprising them are disclosed; these compounds are useful in the treatment of diseases caused by and/or associated with an altered protein kinase activity such as cancer, viral infection, prevention of AIDS development in HIV-infected individuals, cell proliferative disorders, autoimmune and neurodegenerative disorders; also disclosed is a process under Solid Phase Synthesis conditions for preparing the compounds of the invention and chemical libraries comprising a plurality of them.</p>
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FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS (Fri, 07 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.68mm" wi="62.91mm" file="US20170190701A1-20170706-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">and pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocyclic Compound, and methods of using the Fused Tricyclic Heterocyclic Compounds for treating or preventing HIV infection in a subject.</p>
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PEPTIDES MIMICKING HIV-1 VIRAL EPITOPES IN THE V2 LOOP FOR THE GP120 SURFACE ENVELOPE GLYCOPROTEIN (Fri, 07 Jul 2017)
<p id="p-0001" num="0000">The present invention relates to an isolated immunogenic peptide comprising a V2 loop fragment from HIV surface envelope glycoprotein gp120. This peptide binds specifically with antibodies in blood of patients vaccinated with a vaccine that has shown protection from HIV-1 infection, does not react with blood of matched patients who did not receive the vaccine, and can, therefore, elicit anti-HIV-1 antibodies which protect against HIV-1 infection. Other aspects of the present invention relate to an isolated immunogenic polypeptide comprising the peptide inserted into an immunogenic scaffold protein, a vaccine composition comprised of the immunogenic peptide and an immunologically or pharmaceutically acceptable vehicle or excipient as well as methods of inducing an immune response against HIV-1 and methods of detecting HIV-1.</p>
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FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS (Fri, 07 Jul 2017)
The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I) :and pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocyclic Compound, and methods of using the Fused Tricyclic Heterocyclic Compounds for treating or preventing HIV infection in a subject.
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C-3 NOVEL TRITERPENONE DERIVATIVES AS HIV INHIBITORS (Fri, 07 Jul 2017)
The present invention relates to C-3 novel triterpenone derivatives of formula (I); (I) or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, R4, R5, R6, R7, W, ̔m ̕ and ̔n ̕ are as defined herein. The present invention also relates to pharmaceutical compositions comprising compounds of formula (I) and process for preparing them, and their use for the treatment of viral diseases and particularly HIV mediated diseases.
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FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS AS HIV INTEGRASE INHIBITORS (Fri, 07 Jul 2017)
The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocyclic Compound, and methods of using the Fused Tricyclic Heterocyclic Compounds for treating or preventing HIV infection in a subject.
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Fused Tricyclic Heterocyclic compounds as HIV integrase inhibitors (Fri, 07 Jul 2017)
The present invention relates to Fused Tricyclic Heterocyclic Compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein R<sp>1</sp>, R<sp>2</sp> and R<sp>3</sp> are as defined herein. The present invention also relates to compositions comprising at least one Fused Tricyclic Heterocyclic Compound, and methods of using the Fused Tricyclic Heterocyclic Compounds for treating or preventing HIV infection in a subject.
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Thu, 06 Jul 2017)
The present invention is to provide a novel compound shown below, having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Thu, 06 Jul 2017)
The present invention is to provide a novel compound shown below, having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.
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DAPY-DKA (diarylpyrimidine-diketo acid) hybrid HIV (human immunodeficiency virus)-1 inhibitors and preparation method thereof (Sat, 01 Jul 2017)
The invention relates to DAPY-DKA (diarylpyrimidine-diketo acid) hybrid HIV (human immunodeficiency virus)-1 inhibitors and a preparation method thereof. The DAPY-DKA hybrid HIV-1 inhibitors are compounds or pharmaceutical salts thereof represented as formula (1) in the specification, wherein R is selected from hydrogen, C1-5 saturated alkyl groups, C3-5 naphthenic bases and C2-5 alkenyl groups; side chains of DKA or diketo acid ester are located in ortho-positions, meta-positions or para-positions of oxygen atoms of ether bonds. The preparation method of the inhibitors comprises the following steps: 1) 2-(p-cyanoanilino)-4-chloropyrimidine and alkali are mixed with ethyl 4-(p-hydroxyphenyl)-2,4-dioxobutanoate or ethyl 4-(3-hydroxyphenyl)-2,4-dioxobutanoate, a solvent is added, the mixture is uniformly stirred in an inert atmosphere, and a reaction solution is obtained; 2) the reaction solution is heated to be subjected to a nucleophilic substitution reaction, heating is stopped after the reaction, a reaction liquid is subjected to separation and purification, and the DAPY-DKA hybrid HIV-1 inhibitors are obtained.
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CYCLIC COMPOUNDS HAVING A 1,3 DIAMINO-FUNCTIONALITY FOR USE IN THE TREATMENT OF HIV INFECTION (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to compounds, capable of activating HIV expression in reservoir cells, of formula (I) for use in the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.59mm" wi="55.88mm" file="US20170183306A1-20170629-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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SUBSTITUTED N-ACETYL-L-CYSTEINE DERIVATIVES AND RELATED COMPOUNDS (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">Novel substituted N-acetyl-L-cysteine (NAC) derivatives and related compounds and methods of using these compounds for the treatment of diseases and/or conditions, including but not limited to diseases and/or conditions of, or involving, the Central Nervous System (CNS), including schizophrenia adrenoleukodystrophy, mitochondrial diseases (e.g. Leigh syndrome, Alpers' disease, and MELAS), Huntington's disease, trichotillomania, HIV-associated neurocognitive disorder, hypoxic-ischemic encephalopathy, drug craving, and drug addiction.</p>
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BIOMARKERS FOR ASSESSING HIV (Fri, 30 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to metabolic biomarker sets for assessing HIV. In preferred embodiments, the present invention relates to the use of biomarker sets for screening and/or diagnosing HIV infection, for prediction of immunologic response of a mammalian subject to antiretroviral therapy and/or prognosis of HIV disease progression, and for monitoring of HIV disease activity in a mammalian subject. In other embodiments, the invention relates to methods for screening and/or diagnosing HIV infection, for prediction of immunologic response of a mammalian subject to antiretroviral therapy and/or prognosis of HIV disease progression, and for monitoring of HIV disease activity in a mammalian subject, as well as to a kit adapted to carry out the methods. By employing the specific biomarkers and the method according to the present invention it becomes possible to more properly and reliably assess HIV. In particular, it becomes possible to screen for and diagnose HIV in a patient with high accuracy and predict early in advance the patient's therapeutic response to antiretroviral therapy.</p>
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MODIFICATION OF CUPREDOXIN DERIVED PEPTIDES AND METHODS OF USE THEREOF (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">The present invention provides modified cupredoxin derived peptides with pharmacologic activity that have improved pharmacokinetic properties, and methods to use them to treat mammals suffering from various conditions related to the pharmacologic activities. Modifications of the cupredoxin derived peptides include amino acid sequence variants and structural derivations that increase the plasma half-life of the peptide, increase the specific activity of the pharmacologic activity, decrease immunogenicity, and decrease the biotransformation of the peptides. The modified cupredoxin derived peptides can be used in methods to treat mammals for cancer, conditions related to inappropriate angiogenesis, viral and bacterial infections, and specifically HIV and malaria, conditions related to ephrin signaling, and to deliver cargo compounds, including diagnostic compounds, to cancer cell</p>
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Prodrugs of HIV reverse transcriptase inhibitors (Fri, 23 Jun 2017)
<p id="p-0001" num="0000">Compounds of Formula I are described: wherein R<sup>1 </sup>and R<sup>2 </sup>are defined herein. The compounds of Formula I are useful in the inhibition of HIV reverse transcriptase, the prophylaxis and treatment of infection by HIV, and the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.94mm" wi="58.34mm" file="US10004740-20180626-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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ANTIVIRAL OXIME PHOSPHORAMIDE COMPOUNDS (Fri, 23 Jun 2017)
Compounds of Formula I: I and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
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SPIROCYCLIC QUINOLIZINE DERIVATIVES USEFUL AS HIV INTEGRASE INHIBITORS (Fri, 23 Jun 2017)
The present invention relates to spirocyclic quinolizine derivatives and pharmaceutically acceptable salts or prodrug thereof, compositions comprising at least one spirocyclic quinolizine derivative, and methods of using the spirocyclic quinolizine derivatives for treating or preventing HIV infection in a subject.
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BENZOTHIAZOLE COMPOUNDS AND THEIR PHARMACEUTICAL USE (Thu, 22 Jun 2017)
The invention provides compounds of formula I: or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula I.
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Diaryl thienopyrimidine HIV-1 reverse transcriptase inhibitor and preparation method and application thereof (Wed, 21 Jun 2017)
The invention relates to a diaryl thienopyrimidine HIV-1 reverse transcriptase inhibitor and a preparation method and application thereof. The diaryl thienopyrimidine HIV-1 reverse transcriptase inhibitor has a structure shown in the formula I. The invention also relates to a pharmaceutical composition containing the compound shown in the formula I. The invention also provides a use of the compound and a compound composition containing the same type of one or more compounds in preparation of drugs for treating and preventing human immunodeficiency viruses (HIV).
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Crystal form of dolutegravir sodium salt and preparation method for crystal form (Wed, 21 Jun 2017)
The invention relates to a novel crystal form of dolutegravir sodium salt. Compared with an existing crystal form of the dolutegravir sodium salt, the novel crystal form has one or multiple beneficial properties, such as good stability in water, high solubility, uneasiness in moisture absorption, good storage stability and good particle morphology. The invention further relates to a preparation method for the novel crystal form of the dolutegravir sodium salt, a pharmaceutical composition of the novel crystal form as well as a use thereof in preparing a drug for treating and/or preventing HIV-1 infection.
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BETA-HAIRPIN PEPTIDOMIMETICS (Fri, 16 Jun 2017)
<p id="p-0001" num="0000">β-Hairpin peptidomimetics of the general formula cyclo(-Tyr<sup>1</sup>-His<sup>2</sup>-Xaa<sup>3</sup>-Cys<sup>4</sup>-Ser<sup>5</sup>-Xaa<sup>6</sup>-<sup>D</sup>Pro<sup>7</sup>-Xaa<sup>8</sup>-Arg<sup>9</sup>-Tyr<sup>12</sup>-Xaa<sup>13</sup>Xaa<sup>14</sup>-Xaa<sup>15</sup>-Pro<sup>16</sup>-), disulfide bond between Cys<sup>4 </sup>and Cys<sup>11</sup>, and pharmaceutically acceptable salts thereof, with Xaa<sup>3</sup>, Xaa<sup>6</sup>, Xaa<sup>8</sup>, Xaa<sup>13</sup>, Xaa<sup>14 </sup>and Xaa<sup>15 </sup>being amino acid residues of certain types which are defined in the description and the claims, have favorable pharmacological properties and can be used for preventing HIV infections in healthy individuals or for slowing and halting viral progression in infected patients; or where cancer is mediated or resulting from CXCR4 receptor activity; or where immunological diseases are mediated or resulting from CXCR4 receptor activity; or for treating immunosuppression; or during apheresis collections of peripheral blood stem cells and/or as agents to induce mobilization of stem cells to regulate tissue repair.</p> <p id="p-0002" num="0000">These peptidomimetics can be manufactured by a process which is based on a mixed solid-and solution phase synthetic strategy.</p>
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ANTIVIRAL PHOSPHODIAMIDE PRODRUGS OF TENOFOVIR (Fri, 16 Jun 2017)
Compounds of Formula I and pharmaceutically acceptable salts and co-crystals thereof are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
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HUMAN IMMUNODEFICIENCY VIRUS (HIV)-NEUTRALIZING ANTIBODIES (Thu, 15 Jun 2017)
The specification shows a method for obtaining a broadly neutralizing antibody (bNab), including screening memory B cell cultures from a donor PBMC sample for neutralization activity against a plurality of HIV-1 species, cloning a memory B cell that exhibits broad neutralization activity; and rescuing a monoclonal antibody from that memory B cell culture. The resultant monoclonal antibodies may be characterized by their ability to selectively bind epitopes from the Env proteins in native or monomeric form, as well as to inhibit infection of HIV-1 species from a plurality of clades. Compositions containing human monoclonal anti-HIV antibodies used for prophylaxis, diagnosis and treatment of HIV infection are provided. Methods for generating such antibodies by immunization using epitopes from conserved regions within the variable loops of gp120 are provided. Immunogens for generating anti-HIV1 bNAbs are also shown. Furthermore, methods for vaccination using suitable epitopes are shown. More specifically, the invention relates to a broadly neutralizing antibody (bNAb) comprising the polypeptide 4869-K15 (PGT-133), i.e to a monoclonal anti-HIV antibody comprising a heavy chain sequence comprising the amino acid sequence of SEQ ID NO: 420 and a light chain sequence comprising the amino acid sequence SEQ ID NO: 429.
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Hydroxystyrylpyridine mannich bases compound, and preparation method and uses thereof (Wed, 14 Jun 2017)
The invention discloses a novel hydroxystyrylpyridine mannich bases compound (I), and pharmaceutically acceptable salts and a preparation method thereof, a medicine composition, and uses in preparation of a medicine for treating and/or preventing neurodegeneration-related diseases including, but not limited to, vascular dementia, Alzheimer's disease, Parkinson's disease, Huntington's disease, HIV-related dementia, multiple sclerosis, progressive lateral sclerosis, neuropathic pain and glaucoma.
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TREATMENT OF RETROVIRAL RESERVOIRS EXPLOITING OXIDATIVE STRESS (Fri, 09 Jun 2017)
<p id="p-0001" num="0000">Activation of HIV-1 replication causes oxidative stress, which in turn potentiates HIV-1 replication. The common basis for the compounds of the present invention is: A) the capacity of reactivating HIV-1 from latency, and B) the ability to counteract the cellular machinery which activates in order to limit the effects of oxidative stress. In this way, oxidative stress can be potentiated and a “chain reaction” is sparked. This “chain reaction” induces a more efficient reactivation of HIV-1 from latency and, in some cases, induces selective killing of the infected cells. Actions A) and B) can either be carried out by one drug exerting both effects, or obtained by the combined use of distinct drugs. There are two main cellular machineries counteracting oxidative stress, i.e. the thioredoxin (Trx) thioredoxin reductase (TrxR) system and glutathione. Herein, we present drug strategies capable of exerting action B) by blocking either of the two machineries.</p>
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BIOMARKERS FOR ASSESSING HIV (Fri, 09 Jun 2017)
<p id="p-0001" num="0000">The present invention relates to metabolic biomarker sets for assessing HIV. In preferred embodiments, the present invention relates to the use of biomarker sets for screening and/or diagnosing HIV infection, for prediction of immunologic response of a mammalian subject to antiretroviral therapy and/or prognosis of HIV disease progression, and for monitoring of HIV disease activity in a mammalian subject. In other embodiments, the invention relates to methods for screening and/or diagnosing HIV infection, for prediction of immunologic response of a mammalian subject to antiretroviral therapy and/or prognosis of HIV disease progression, and for monitoring of HIV disease activity in a mammalian subject, as well as to a kit adapted to carry out the methods. By employing the specific biomarkers and the method according to the present invention it becomes possible to more properly and reliably assess HIV. In particular, it becomes possible to screen for and diagnose HIV in a patient with high accuracy and predict early in advance the patient's therapeutic response to antiretroviral therapy.</p>
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Oxolupene derivatives (Fri, 09 Jun 2017)
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formulas I and II. These compounds are useful for the treatment of HIV and AIDS.
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C17-aryl substituted betulinic acid analogs (Fri, 09 Jun 2017)
Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, betulinic acid derivatives that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula (I). These compounds are useful for the treatment of HIV and AIDS.
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一种嘧啶类杂环化合物、嘧啶类杂环化合物盐以及制备方法和应用 (Thu, 01 Jun 2017)
本发明提供了一种嘧啶类杂环化合物、嘧啶类杂环化合物盐以及制备方法和应用,本发明提供的式(I)的嘧啶类杂环化合物,通过选择特定的Rq,使得得到的化合物作为治疗或预防抗HIV病毒的药物时,不仅具有很好的耐药性和长的半衰期,而且该化合物活性高,毒性低且稳定性高。
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Process for making reverse transcriptase inhibitors (Wed, 31 May 2017)
<p id="p-0001" num="0000">The present invention is directed to a novel process for synthesizing 3-(substituted phenoxy)-1-[(5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl])-pyridin-2(1H)-one derivatives. The compounds synthesized by the processes of the invention are HIV reverse transcriptase inhibitors useful for inhibiting reverse transcriptase, HIV replication and the treatment of human immunodeficiency virus infection in humans.</p>
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SPIROCYCLIC PYRIDOTRIAZINE DERIVATIVES USEFUL AS HIV INTEGRASE INHIBITORS (Sat, 27 May 2017)
The present invention relates to Spirocyclic Pyridotriazine Derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, B, X, Y, R1, R2 and R10 are as defined herein. The present invention also relates to compositions comprising at least one Spirocyclic Pyridotriazine Derivative, and methods of using the Spirocyclic Pyridotriazine Derivatives for treating or preventing HIV infection in a subject.
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AMIDO-SUBSTITUTED PYRIDOTRIAZINE DERIVATIVES USEFUL AS HIV INTEGRASE INHIBITORS (Sat, 27 May 2017)
The present invention relates to Amido-Substituted Pyridotriazine Derivatives of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein B, X, Y, R, R1, R2 and R10 are as defined herein. The present invention also relates to compositions comprising at least one Amido-Substituted Pyridotriazine Derivative, and methods of using the Amido-Substituted Pyridotriazine Derivatives for treating or preventing HIV infection in a subject.
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 26 May 2017)
<p id="p-0001" num="0000">The present invention is to provide a novel compound (I) shown below, having the anti-virus activity; particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="69.85mm" file="US20170145033A1-20170525-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">(wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">Z<sup>1 </sup>is NR<sup>4</sup>;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is hydrogen or lower alkyl;</li> <li id="ul0002-0003" num="0000">X is a single bond, a hetero atom group selected from O, S, SO, SO<sub>2 </sub>and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene;</li> <li id="ul0002-0004" num="0000">R<sup>2 </sup>is optionally substituted aryl;</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and</li> <li id="ul0002-0006" num="0000">R<sup>4 </sup>and Z<sup>2 </sup>part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.</li> </ul> </li> </ul> </p>
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METHODS FOR DETERMINING RESISTANCE OR SUSCEPTIBILITY TO HIV ENTRY INHIBITORS (Fri, 26 May 2017)
<p id="p-0001" num="0000">The invention provides a method for determining whether a human immunodeficiency virus is likely to be more resistant to a viral entry inhibitor than a reference HIV. In certain aspects, the methods comprise comparing the length of one or more variable regions of an envelope protein of the HIV or a number of glycosylation sites on the envelope protein of the HIV to a length of one or more corresponding variable regions of an envelope protein of the reference HIV or a number of glycosylation sites on the envelope protein of the reference HIV, wherein the HIV is likely to be more resistant to the CD4 binding site entry inhibitor than the reference HIV when the HIV has longer variable regions than the reference HIV or the HIV has more glycosylation sites than the reference HIV.</p>
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HIV逆転写酵素阻害剤としての4’置換ヌクレオシド誘導体 (Fri, 26 May 2017)
<p num=""> 本発明は、式I<br/>【化1】<br/><img id="000079" he="7" wi="78" file="2017512797.tif" img-format="tif" img-content="drawing"/><br/>の4’置換ヌクレオシド誘導体(式I)、ならびにHIV逆転写酵素の阻害、HIVによる感染症の予防、HIVによる感染症の治療、およびAIDSおよび/またはARCの予防、治療およびそれらの発症または進行の遅延におけるそれらの使用を対象とする。</p>
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HIV逆転写酵素阻害剤のプロドラッグ (Fri, 26 May 2017)
<p num=""> 式Iの化合物(R<sup>1</sup>およびR<sup>2</sup>は本明細書で定義されている。)について記載されている。式Iの化合物は、HIV逆転写酵素の阻害、HIVによる感染の予防および治療、ならびにAIDSの予防、発症もしくは進行の遅延および治療において有用である。当該化合物は、適宜に他の抗ウィルス剤、免疫調節剤、抗生物質またはワクチンと組み合わせて、医薬組成物における成分として用いることができる。<br/> 【化1】<br/><img id="000109" he="48" wi="79" file="2017512802.tif" img-format="tif" img-content="drawing"/></p>
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Modulators of toll-like receptors for the treatment of hiv (Thu, 25 May 2017)
Provided are methods, uses, pharmaceutical regimens, pharmaceutical compositions, and kits comprising modulators of TLR7, including those of Formula (II); and pharmaceutically acceptable salts thereof, useful in treating HIV infections.
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Compounds for the treatment of HIV (Fri, 19 May 2017)
<p id="p-0001" num="0000">The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating a Retroviridae viral infection including an infection caused by the HIV virus.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.63mm" wi="50.63mm" file="US09944619-20180417-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Chemokine CXCR4 and CCR5 Receptor Modulators and Uses Related Thereto (Fri, 19 May 2017)
<p id="p-0001" num="0000">The disclosure relates to chemokine receptor modulators and uses related thereto. In certain embodiments, the disclosure relates to pharmaceutical compositions comprising compounds disclosed herein or pharmaceutically acceptable salts or prodrugs thereof. In certain embodiments, the compositions disclosed herein are used for managing chemokine related conditions, typically prevention or treatment of viral infections such as HIV or for managing cancer.</p>
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MULTIFUNCTIONAL BIODEGRADABLE PEG NANOCARRIER-BASED HYDROGELS FOR PREVENTING HIV TRANSMISSION (Fri, 19 May 2017)
<p id="p-0001" num="0000">A multifunctional polyethylene glycol-based hydrogel that includes a multi-arm polyethylene glycol cross-linking unit covalently bound to at least four multi-arm polyethylene glycol nanocarrier units, wherein each nanocarrier unit includes an agent coupled to the nanocarrier unit and each agent is selected from pH-lowering agents, bioadhesion agents, microbicidal-spermicidal agents, and agents that inhibit free and cell-associated HIV binding, provided that each nanocarrier unit comprises a different agent.</p>
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POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE (Fri, 12 May 2017)
<p id="p-0001" num="0000">Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="67.73mm" file="US20170128444A1-20170511-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">including stereoisomers and pharmaceutically acceptable salts thereof, wherein L, R<sup>5</sup>, W, X, Y<sup>1</sup>, Y<sup>2</sup>, and Z are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.</p>
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Polycyclic-carbamoylpyridone compounds and their pharmaceutical use (Fri, 12 May 2017)
<p id="p-0001" num="0000">Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="64.69mm" file="US09700554-20170711-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> including stereoisomers and pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>, X, Y<sup>1</sup>, Y<sup>2</sup>, or L are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. </p>
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NOVEL BETULINIC PROLINE IMIDAZOLE DERIVATIVES AS HIV INHIBITORS (Fri, 12 May 2017)
<p id="p-0001" num="0000">The invention relates to novel betulinic proline substituted derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="51.05mm" wi="74.93mm" file="US20170129916A1-20170511-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Betulinic proline imidazole derivatives as HIV inhibitors (Fri, 12 May 2017)
<p id="p-0001" num="0000">The present invention relates to novel betulinic proline imidazole derivatives and related compounds, compositions useful for therapeutic treatment of viral diseases and particularly HIV mediated diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="48.68mm" wi="76.03mm" file="US09868758-20180116-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Polycyclic-carbamoylpyridone compounds and their pharmaceutical use (Fri, 05 May 2017)
<p id="p-0001" num="0000">Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (Ia):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="63.84mm" file="US09795602-20171024-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> including stereoisomers and pharmaceutically acceptable salts thereof, wherein A′, R<sup>1</sup>, R<sup>2 </sup>and R<sup>3 </sup>are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. </p>
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HIV REPLICATION INHIBITING PYRIMIDINES (Fri, 05 May 2017)
<p id="p-0001" num="0000">This invention concerns HIV replication inhibitors of formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.81mm" wi="65.11mm" file="US20170121292A1-20170504-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, wherein the ring containing -a<sup>1</sup>=a<sup>2</sup>-a<sup>3</sup>=a<sup>4</sup>- and -b<sup>1</sup>=b<sup>2</sup>-b<sup>3</sup>=b<sup>4</sup>- represents phenyl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl; n is 0 to 5; m is 1 to 4; R<sup>1 </sup>is hydrogen; aryl; formyl; C<sub>1-6</sub>alkylcarbonyl; C<sub>1-6</sub>alkyl; C<sub>1-6</sub>alkyloxycarbonyl; substituted C<sub>1-6</sub>alkyl, C<sub>1-6</sub>alkylcarbonyl, C<sub>1-6</sub>alkyloxycarbonyl, C<sub>1-6</sub>alkylcarbonyloxy; substituted C<sub>1-6</sub>alkyloxyC<sub>1-6</sub>alkylcarbonyl; R<sup>2 </sup>is hydroxy, halo, optionally substituted C<sub>1-6</sub>alkyl, C<sub>3-7</sub>cycloalkyl, optionally substituted C<sub>2-6</sub>alkenyl, optionally substituted C<sub>2-6</sub>alkynyl, C<sub>1-6</sub>alkyloxy, C<sub>1-6</sub>alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C<sub>1-6</sub>alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, —S(═O)<sub>p</sub>R<sup>6</sup>, —NH—S(═O)<sub>p</sub>R<sup>6</sup>, —C(═O)R<sup>6</sup>, —NHC(═O)H, —C(═O)NHNH<sub>2</sub>, —NHC(═O)R<sup>6</sup>, —C(═NH)R<sup>6 </sup>or a 5-membered heterocycle; X<sub>1 </sub>is —NR<sup>5</sup>—, —NH—NH—, —N═N—, —O—, —C(═O)—, C<sub>1-4</sub>alkanediyl, —CHOH—, —S—, —S(═O)<sub>p</sub>—, —X<sub>2</sub>—C<sub>1-4</sub>alkanediyl- or —C<sub>1-4</sub>alkanediyl-X<sub>2</sub>—; R<sup>3 </sup>is NHR<sup>13</sup>; NR<sup>13</sup>R<sup>14</sup>; —C(═O)—NHR<sup>13</sup>; —C(═O)—NR<sup>13</sup>R<sup>14</sup>; —C(═O)—R<sup>15</sup>; —CH═N—NH—C(═O)—R<sup>16</sup>; substituted C<sub>1-6</sub>alkyl; optionally substituted C<sub>1-6</sub>alkyloxyC<sub>1-6</sub>alkyl; substituted C<sub>2-6</sub>alkenyl; substituted C<sub>2-6</sub>alkynyl; C<sub>1-6</sub>alkyl substituted with hydroxy and a second substituent; —C(═N—O—R<sup>8</sup>)—C<sub>1-4</sub>alkyl; R<sup>7</sup>; or —X<sub>3</sub>—R<sup>7</sup>; R<sup>4 </sup>is halo, hydroxy, C<sub>1-6</sub>alkyl, C<sub>3-7</sub>cycloalkyl, C<sub>1-6</sub>alkyloxy, cyano, nitro, polyhaloC<sub>1-6</sub>alkyl, polyhaloC<sub>1-6</sub>alkyloxy, aminocarbonyl, C<sub>1-6</sub>alkyloxycarbonyl, C<sub>1-6</sub>alkylcarbonyl, formyl, amino, mono- or di(C<sub>1-4</sub>alkyl)amino; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them.</p>
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인간 면역결핍 바이러스 복제의 억제제로서 이미다조[1,2-A]피리딘 유도체 (Thu, 27 Apr 2017)
본 발명은 일반적으로 조성물 및 인간 면역결핍 바이러스 (HIV) 감염을 치료하는 방법을 포함하는, 화학식 I의 화합물에 관한 것이다. 본 발명은 신규한 HIV의 억제제, 그러한 화합물을 함유하는 약학적 조성물, 및 HIV 감염의 치료에 이러한 화합물을 이용하는 방법을 제공한다. TIFF pct00055.tif 41 70
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Tricyclic heterocycle derivatives having HIV replication inhibitory effect (Fri, 21 Apr 2017)
<p id="p-0001" num="0000">The present invention provides the following compound having anti-HIV activity of formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.12mm" wi="57.40mm" file="US09975906-20180522-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein, A<sup>1 </sup>is C, CR<sup>1A </sup>or N; <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">A<sup>2 </sup>is C, CR<sup>2A</sup>, or N;</li> <li id="ul0001-0002" num="0000">A<sup>3 </sup>is CR<sup>3A</sup>, CR<sup>3A</sup>R<sup>3B</sup>, N, NR<sup>3C</sup>, O, S, SO, or SO<sub>2</sub>;</li> <li id="ul0001-0003" num="0000">A<sup>4 </sup>is CR<sup>4A</sup>, CR<sup>4A</sup>R<sup>4B</sup>, N, NR<sup>4C</sup>, O, S, SO, or SO2;</li> <li id="ul0001-0004" num="0000">A<sup>5 </sup>is C, CR<sup>5A</sup>, or N;</li> <li id="ul0001-0005" num="0000">T<sup>1 </sup>ring is substituted or unsubstituted monocyclic carbocycle or substituted or unsubstituted monocyclic heterocycle;</li> <li id="ul0001-0006" num="0000">R<sup>1 </sup>is halogen, cyano, nitro or —X<sup>1</sup>—R<sup>11</sup>;</li> <li id="ul0001-0007" num="0000">R<sup>2 </sup>is substituted or unsubstituted alkyl and the like;</li> <li id="ul0001-0008" num="0000">n is 1 or 2;</li> <li id="ul0001-0009" num="0000">R<sup>3 </sup>is hydrogen, substituted or unsubstituted aromatic carbocyclyl;</li> <li id="ul0001-0010" num="0000">R<sup>4 </sup>is hydrogen or a carboxy protecting group;</li> <li id="ul0001-0011" num="0000">the other symbols are as specified in the description.</li> </ul> </p>
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C-3 NOVEL TRITERPENONE WITH C-28 UREA DERIVATIVES AS HIV INHIBITORS (Fri, 21 Apr 2017)
The present invention relates to C-3 novel triterpenone with C-28 urea derivatives of formula (I); or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, W, J and X are as defined herein. The present invention also relates to pharmaceutical compositions comprising compounds of formula (I) useful for the treatment of viral diseases and particularly HIV mediated diseases.
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Nucleoside phosphoramidate type compound with HBV/HIV resistance activity and salt and application of nucleoside phosphoramidate type compound (Thu, 20 Apr 2017)
The invention relates to a nucleoside phosphoramidate type compound with HBV/HIV resistance activity, an isomer of the nucleoside phosphoramidate type compound, pharmaceutically-acceptable salt of the nucleoside phosphoramidate type compound, a solvate or crystal of the nucleoside phosphoramidate type compound, a medicine composition of the nucleoside phosphoramidate type compound, and application of the nucleoside phosphoramidate type compound. According to related novel non-cyclic nucleoside phosphoramidate, on the phosphoramidate part, amino acid is D-amino-acid. D-amino-acid ester is introduced in the prodrug, and a new non-cyclic nucleotide amide compound which has higher chemical stability, higher lipid solubility and higher virus inhibition activity is expected to be obtained. By means of the creative design, the virus resistance activity of medicine is improved, solubility and pharmacokinetics characteristics of the medicine are improved, the concentration ratio in tissue cells and plasma is increased, and therefore the curative effect, safety and tolerance of the medicine can be improved, and very good clinical application prospects are achieved.
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ハロアルキル置換基を有する非芳香族環により3位で置換されている、HIV成熟阻害活性を有するトリテルペノイド (Fri, 14 Apr 2017)
<p num=""> 薬物及び生体に影響を与える特性を有する化合物、それらの医薬組成物及び使用方法が記載される。特に、特有の抗ウイルス活性を有するトリテルペノイドが、HIV成熟阻害剤として提供され、式Iの化合物として表され、ここでXは、C<sub>4〜8</sub>シクロアルキル、C<sub>4〜8</sub>シクロアルケニル、C<sub>4〜9</sub>スピロシクロアルキル、C<sub>4〜9</sub>スピロシクロアルケニル、C<sub>4〜8</sub>オキサシクロアルキル、C<sub>4〜8</sub>ジオキサシクロアルキル、C<sub>6〜8</sub>オキサシクロアルケニル、C<sub>6〜8</sub>ジオキサシクロアルケニル、C<sub>6</sub>シクロジアルケニル、C<sub>6</sub>オキサシクロジアルケニル、C<sub>6〜9</sub>オキサスピロシクロアルキル及びC<sub>6〜9</sub>オキサスピロシクロアルケニル環から選択され、XはAで置換されており、Aは、-C<sub>1〜6</sub>アルキル-ハロである。これらの化合物は、HIV及びAIDSの治療に有用である。<br/> 【化1】<br/><img id="000307" he="60" wi="97" file="2017510659.tif" img-format="tif" img-content="drawing"/><br/>【選択図】なし</p>
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COMPOUNDS AND COMBINATIONS FOR THE TREATMENT OF HIV (Fri, 07 Apr 2017)
Provided are 3-cyano-1H-1,2,4-triazol-1-yl acetamide compounds, compositions, combinations, kits, uses, and methods for treating HIV in a human being using such compounds or combinations with proteasome inhibitors.
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Compounds and combinations for the treatment of HIV (Fri, 07 Apr 2017)
Provided are 3-cyano-1H-1,2,4-triazol-1-yl acetamide compounds, compositions, combinations, kits, uses, and methods for treating HIV in a human being using such compounds or combinations with proteasome inhibitors.
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HIV-1 protease inhibitors and uses thereof (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">Various embodiments of the present invention are directed to compounds of the formula (I) or a pharmaceutically acceptable salt, polymorph, prodrug, solvate or clathrate thereof, wherein X<sup>1</sup>, X<sup>2</sup>, X<sup>3</sup>, R<sup>1</sup>, R<sup>2</sup>, R<sup>11</sup>, and n are defined herein. These compounds are useful as inhibitors of HIV-1 protease and, as a result, are useful in the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="37.59mm" wi="68.24mm" file="US09670225-20170606-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Therapeutic compounds (Fri, 31 Mar 2017)
<p id="p-0001" num="0000">The invention provides compounds of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="69.85mm" file="US09879023-20180130-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula I, intermediates useful for preparing compounds of formula I and therapeutic methods for treating the proliferation of the HIV virus, treating AIDS or delaying the onset of AIDS or ARC symptoms in a mammal using compounds of formula I. </p>
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COMPOUNDS WITH HIV MATURATION INHIBITORY ACTIVITY (Fri, 31 Mar 2017)
The present invention relates to compounds characterized by having a structure according to the following Formula (I), or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
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MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE (Fri, 31 Mar 2017)
Provided are compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of HIV; including the prevention of the progression of AIDS and general immunosuppression.
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MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE (Fri, 31 Mar 2017)
Provided are compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of HIV; including the prevention of the progression of AIDS and general immunosuppression.
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HIV ANTIBODY COMPOSITIONS AND METHODS OF USE (Fri, 31 Mar 2017)
This invention relates to novel anti-HIV antibodies that can be used in the treatment and detection of human immunodeficiency virus (HIV). These antibodies exhibit a high degree of sensitivity and can provide a broad range of specificity.
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4'-SUBSTITUTED NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS AND PREPARATIONS THEREOF (Fri, 31 Mar 2017)
The present invention is directed to 4'-substituted nucleoside derivatives of Formula (I) and their use in the inhibition of HIV reverse transcriptase, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS and/or ARC. The present invention also provides processes for the preparation of 4'-substituted nucleoside derivatives of Formula (I) and derivatives thereof.
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Compounds with HIV maturation inhibitory activity (Fri, 31 Mar 2017)
The present invention relates to compounds characterized by having a structure according to the following Formula (I), or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
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Modulators of indoleamine 2,3-dioxygenase (Fri, 31 Mar 2017)
Provided are compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of HIV; including the prevention of the progression of AIDS and general immunosuppression.
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Modulators of indoleamine 2,3-dioxygenase (Fri, 31 Mar 2017)
Provided are compounds and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of HIV; including the prevention of the progression of AIDS and general immunosuppression.
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4'-substituted nucleoside reverse transcriptase inhibitors and preparations thereof (Fri, 31 Mar 2017)
The present invention is directed to 4'-substituted nucleoside derivatives of Formula (I) and their use in the inhibition of HIV reverse transcriptase, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS and/or ARC. The present invention also provides processes for the preparation of 4'-substituted nucleoside derivatives of Formula (I) and derivatives thereof.
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新規な3−インドール置換誘導体、医薬組成物、および使用方法 (Fri, 24 Mar 2017)
<p num=""> 本発明は、式(I)の化合物、または薬学的に許容できるその鏡像異性体、塩、もしくは溶媒和物に関する。本発明はさらに、式Iの化合物のTDO2阻害薬としての使用に関する。本発明はまた、HIV、うつ病、および肥満の治療および/または予防のための、式Iの化合物の使用に関する。本発明はまた、式(I)の化合物の製造方法に関する。<br/>【化1】<br/><img id="000338" he="112" wi="113" file="2017507983.tif" img-format="tif" img-content="drawing"/></p>
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複製型組み換えアデノウイルスベクター、組成物およびこれらの使用方法 (Fri, 24 Mar 2017)
<p num="">ヒトアデノウイルス血清型26またはヒトアデノウイルス血清型35に由来する複製型組み換えアデノウイルスベクターが説明されている。この複製型組み換えアデノウイルスベクターの複製能は、対応する野生型アデノウイルスの複製能と比較して減弱されている。この複製型組み換えアデノウイルスベクターを、in vivoでの異種遺伝子の安定した発現に使用することができる。更に説明されているのは、この組み換えアデノウイルスベクターを使用して対象中で免疫応答を誘導するためのおよび免疫原性ヒト免疫不全ウイルス(HIV)感染に対するワクチンを対象に接種するための組成物および方法である。</p>
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Phenyl and tertbutylacetic acid substituted pyridinones having anti-HIV effects (Thu, 23 Mar 2017)
Compounds of Formula I are disclosed and methods of treating viral invections with compositions comprising such compounds. Formula I
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TRICYCLIC HETEROCYCLIC DERIVATIVE HAVING HIV REPLICATION-INHIBITING EFFECT (Thu, 23 Mar 2017)
The present invention provides the following compound having anti-HIV activity of formula: wherein, A 1 is C, CR 1A or N; A 2 is C, CR 2A , or N; A 3 is CR 3A , CR 3A R 3B , N, NR 3c O, S, SO, or SO 2 ; A 4 is CR 4A , CR 4A R 4B , N, NR 4C O, S, SO, or SO2; A 5 is C, CR 5A , or N; T 1 ring is substituted or unsubstituted monocyclic carbocycle or substituted or unsubstituted monocyclic heterocycle; R 1 is halogen, cyano, nitro or -X 1 -R 11 ; R 2 is substituted or unsubstituted alkyl and the like; n is 1 or 2; R 3 is hydrogen, substituted or unsubstituted aromatic varbocyclyl; R 4 is hydrogen or a carboxy protecting group; the other symbols are as specified in the description.
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PIPERAZINE DERIVATIVES AS HIV PROTEASE INHIBITORS (Fri, 17 Mar 2017)
<p id="p-0001" num="0000">The present invention is directed to compounds of Formula I pharmaceutical compositions comprising the same, and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="32.43mm" wi="58.59mm" file="US20170073354A1-20170316-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Imidazo[1,2-a]pyridine derivatives for use as inhibitors of human immunodeficiency virus replication (Fri, 17 Mar 2017)
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
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METHODS OF TREATING METABOLIC DISORDERS ASSOCIATED WITH LIPODYSTROPHIES AND DEFECTS IN INSULIN PRODUCTION OR SIGNALING (Fri, 10 Mar 2017)
<p id="p-0001" num="0000">The invention relates to the identification of new therapeutic methods for the FGF21 polypeptide or protein, or mutants, variants, and fusions thereof, for instance, in treating metabolic diseases associated defects in insulin signaling (e.g. insulin receptor mutation disorders (INSR disorders) and/or autoimmune insulin receptor disorders (Type B insulin Resistance)), defects in insulin production such as type 1 diabetes mellitus, mixed dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and other metabolic disorders, and various lipodystrophies such as HIV-HAART induced partial-lipodystrophy, and in reducing the mortality and morbidity of critically ill patients.</p>
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SMALL-MOLECULE INHIBITORS OF HIV-1 REPLICATION (Fri, 10 Mar 2017)
We developed a time-resolved fluorescence resonance energy transfer high-throughput screening assay (HTS-TR-FRET), to identify inhibitors of capsid dimerization, using the C-terminal domain (CTD) of HIV-1 capsid. This assay was used to screen the Library of Pharmacologically Active Compounds, composed of 1,280 in vivo active drugs, and identified Ebselen, an organoselenium compound, as a potent inhibitor of HIV-1 capsid CTD dimerization. Nuclear magnetic resonance (NMR) spectroscopic analysis confirmed the direct interaction of Ebselen with the HIV-1 capsid CTD and dimer dissociation when Ebselen is in two-fold molar excess. Electrospray ionization mass spectrometry (ESI-MS) reveals Ebselen covalently binds the HIV-1 capsid CTD, likely via a selenylsulfide linkage with Cys 198 and Cys 218. This compound presents anti-HIV activity in single- and multiple-round of infection in permissive cell lines as well as in primary peripheral blood mononuclear cells.
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Antiretroviral agents (Fri, 10 Mar 2017)
Compounds of formula I: or salts thereof are disclosed. Also disclosed are pharmaceutical compositions comprising a compound of formula I, processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula (I) and therapeutic methods for treating a <i>Retroviridae</i> viral infection including an infection caused by the HIV virus.
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HIV複製阻害剤 (Sat, 04 Mar 2017)

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Substituted 2,3,4,5,7,9,13,13a-octahydropyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]OXAZEPINES and methods for treating viral infections (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="65.28mm" file="US09732092-20170815-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> including stereoisomers and pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>, X, W, Y<sup>1</sup>, Y<sup>2</sup>, Z<sup>1</sup>, and Z<sup>4 </sup>are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. </p>
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TRITERPENOIDS WITH HIV MATURATION INHIBITORY ACTIVITY (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">Compounds having drug and bio-affecting properties, their pharmaceutical compositions and methods of use are set forth. In particular, triterpenoids that possess unique antiviral activity are provided as HIV maturation inhibitors, as represented by compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="40.64mm" wi="69.51mm" file="US20170056420A1-20170302-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">with X selected from C<sub>4-8 </sub>cycloalkyl, C<sub>4-8 </sub>cycloalkenyl, C<sub>4-9 </sub>spirocycloalkyl, C<sub>4-9 </sub>spirocycloalkenyl, C<sub>4-8 </sub>oxacycloalkyl, C<sub>4-8 </sub>dioxacycloalkyl, C<sub>6-8 </sub>oxacycloalkenyl, C<sub>6-8 </sub>dioxacycloalkenyl, C<sub>6 </sub>cyclodialkenyl, C<sub>6 </sub>oxacyclodialkenyl, C<sub>6-9 </sub>oxaspirocycloalkyl and C<sub>6-9 </sub>oxaspirocycloalkenyl ring, such that X is substituted with A, wherein A is —C<sub>1-6 </sub>alkyl-halo. These compounds are useful for the treatment of HIV and AIDS.</p>
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Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication (Fri, 03 Mar 2017)
<p id="p-0001" num="0000">The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV integrase, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.09mm" wi="44.70mm" file="US09834566-20171205-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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白桦脂醇的衍生物 (Thu, 02 Mar 2017)
本发明涉及以具有按照下列式I:(I)的结构为特征的化合物,或其可药用盐。本发明的化合物可用于治疗或预防HIV。
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5−フェノキシ−3H−ピリミジン−4−オン誘導体およびHIV逆転写酵素阻害薬としてのそれらの使用 (Sat, 25 Feb 2017)

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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 24 Feb 2017)
Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
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Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication (Fri, 24 Feb 2017)
Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
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Inhibitors of human immunodeficiency virus replication (Thu, 23 Feb 2017)
Compounds of Formula I with activity against HIV, including pharmaceutical compositions and methods for using these compounds in treating human immunodeficiency virus (HIV) infection, are set forth: Formula :(I)
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Amyloid precursor protein (APP) based Ã#-secretase inhibitor peptides, and methods of use (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">The present invention provides fusion peptides, compositions, methods and kits for treating, reducing the risk of, lessening the severity of, preventing, or delaying the onset of amyloid-related disorders, such as Alzheimer's disease and HIV associated neurocognitive impairment.</p>
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1-(3-AMINOPROPYL) SUBSTITUTED CYCLIC AMINE COMPOUNDS, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITIONS AND USES THEREOF (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">Provided are 1-(3-aminopropyl) substituted cyclic amine compounds as represented by formula (I), pharmaceutically acceptable salts, enantiomers, diastereoisomers, racemates and mixtures thereof, and a method of synthesizing said 1-(3-aminopropyl) substituted cyclic amine compounds by using aromatic heterocyclic formaldehyde as raw material. Said compounds can be used as CCR 5 antagonist for the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.65mm" wi="67.39mm" file="US20170044187A1-20170216-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Antiviral beta-amino acid ester phosphodiamide compounds (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">Compounds of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="35.22mm" wi="69.26mm" file="US09822138-20171121-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines. </p>
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Selective HDAC1 and HDAC2 inhibitors (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">Provided herein are compounds, pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with HDAC activity, particularly diseases or disorders that involve activity of HDAC1 and/or HDAC2. Such diseases include cancer, sickle-cell anemia, beta-thalassemia, and HIV.</p>
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TETRA-O-SUBSTITUTED BUTANE-BRIDGE MODIFIED NDGA DERIVATIVES, THEIR SYNTHESIS AND PHARMAECUTICAL USE (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">The present invention relates to nordihydroguaiaretic acid derivative compounds, namely, butane bridge modified nordihydroguaiaretic acid (NDGA) compounds and butane bridge modified tetra-O-substituted NDGA compounds, pharmaceutical compositions containing them, methods of making them, and methods of using them and kits including them for the treatment of diseases and disorders, in particular, diseases resulting from or associated with a virus infection, such as HIV infection, HPV infection, or HSV infection, an inflammatory disease, such as various types of arthritis and inflammatory bowel diseases, metabolic diseases, such as diabetes and hypertension, or a proliferative disease, such as diverse types of cancers.</p>
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SUBSTITUTED SPIROPYRIDO[1,2-a]PYRAZINE DERIVATIVE AND MEDICINAL USE THEREOF AS HIV INTEGRASE INHIBITOR (Fri, 17 Feb 2017)
<p id="p-0001" num="0000">Provided is a substituted spiropyrido[1,2-a]pyrazine derivative or a pharmaceutically acceptable salt thereof, which is useful as an anti-HIV agent. The present invention relates to a compound represented by the following formula [I] or [II] or a pharmaceutically acceptable salt thereof:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="78.57mm" wi="75.10mm" file="US20170044156A1-20170216-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein each symbol is as defined in the specification.</p>
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新規な3−(インドール−3−イル)−ピリジン誘導体、医薬組成物、および使用方法 (Fri, 17 Feb 2017)
<p num=""> 本発明は、式(I)の化合物、または薬学的に許容できるその鏡像異性体、塩、もしくは溶媒和物に関する。本発明はさらに、式Iの化合物のTDO2阻害薬としての使用に関する。本発明はまた、がん、パーキンソン病、アルツハイマー病、およびハンチントン病などの神経変性障害、HCVおよびHIVなどの慢性ウイルス感染症、うつ病、および肥満の治療および/または予防のための、式Iの化合物の使用に関する。本発明はまた、式Iの化合物の製造方法に関する。<br/>【化1】<br/><img id="000214" he="160" wi="156" file="2017505346.tif" img-format="tif" img-content="drawing"/></p>
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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 17 Feb 2017)
Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS. In the compounds of formula (I), R1 is selected from H, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, (alkoxy)alkoxyalkyl, or (R6)alkyl; R2 is phenyl substituted with 1 R7 substituent and with 0-3 substituents selected from halo, alkyl, haloalkyl, alkoxy, and haloalkoxy; or R2 is selected from tetrahydroisoquinolinyl, ((Ar1)alkyl)tetrahydroisoquinolinyl, or ((N-alkoxycarbonyl)tetrahydroisoquinolinyl; R3 is is selected from tetrahydroisoquinolinyl or decahydroisoquinolinyl and is substituted with 0-3 substituents selected from halo, alkyl, and haloalkyl; or R3 is a [5-7.3-7.0-2] fused or bridged bicyclic amine and is substituted with 0-3 alkyl substituents; or R3 is selected from azetidinyl, pyrrolidinyl, piperidinyl, or homopiperidinyl and contains a spirocyclic moiety wherein the spirocyclic moiety, including the carbon atom to which it is attached, forms C3-7 cycloalkane, tetrahydrofuranyl, tetrahydropyranyl, pyrrolidinyl, N-alkylpyrrolidinyl, piperidinyl, N-alkylpiperidinyl, homopiperidinyl, or N-alkylpiperidinyl, and wherein the spirocyclic moiety is substituted with 0-3 halo or alkyl substituents; R4 is selected from alkyl or haloalkyl; R5 is selected from H, alkyl, haloalkyl, hydroxyalkyl, alkoxyalkyl, (alkoxy)alkoxyalkyl, or (R6)alkyl; R6is selected from (oxetanyl)oxy, ((oxetanyl)alkoxy)alkyl, (tetrahydropyranyloxy)alkyl, (tetrahydropyranyl)alkoxy)alkyl, or (Rg)(R9)N; R7 is selected from (Ar1)alkoxy or ((Ar1)alkyl)HNCO; R8 is selected from hydrogen, alkyl, (cycloalkyl)alkyl, alkoxyalkyl, (tetrahydropyanyl)alkyl, tetrahydropyanyl, or alkoxyphenyl; R9 is selected from hydrogen or alkyl; or (R8)(R9)N taken together is selected from azetidinyl, pyrrolidinyl, piperidinyl, (spirocyclobutyl)piperidinyl, piperazinyl, or morpholinyl; and Ar1 is phenyl substituted with 0-3 substituents selected from halo, alkyl, haloalkyl, alkoxy, and haloalkoxy.
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5-(N-FUSED TRICYCLIC ARYL TETRAHYDROISOQUINOLIN-6-YL) PYRIDIN-3- YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 17 Feb 2017)
Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
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IMIDAZOPYRIDINE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 17 Feb 2017)
Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 17 Feb 2017)
Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
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3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 17 Feb 2017)
A compound of Formula (I) is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula (I) as TD02 inhibitors. The invention also relates to the use of the compounds of Formula I for the treatment and/or prevention of cancer, neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease and Huntington's disease, chronic viral infections such as HCV and HIV, depression, and obesity. The invention also relates to a process for manufacturing compounds of Formula (I).
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5-(N-[6,5]-FUSED BICYCLIC ARYL TETRAHYDROISOQUINOLIN-6-YL) PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 17 Feb 2017)
Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
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5-(N-BENZYL TETRAHYDROISOQUINOLIN-6-YL) PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 17 Feb 2017)
Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS. In the compounds of formula (I), R1 is selected from hydrogen, alkyl, or cycloalkyi; R2 is selected from tetrahydroisoquinolinyl and is substituted with 1 R6 substituent and also with 0-3 halo or alkyl substituents; R3 is selected from azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, homopiperidinyl, homopiperazinyl, or homomorpholinyl, and is substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyi, alkoxy, and haloalkoxy; R4 is selected from alkyl or haloalkyi; R5 is alkyl; R6 is selected from Ar1, (Ar1)alkyl, (chromanyl)alkyl, cyanocycloalkyl or (dihydrobenzodioxinyl)alkyl; and Ar1 is phenyl substituted with 0-5 substituents selected from cyano, halo, alkyl, cycloalkyi, haloalkyi, hydroxy, alkoxy, haloalkoxy, (hydroxy)alkoxy, (alkoxy)alkoxy, phenoxy, benzyloxy, carboxy, phenyl, and cyanocycloalkyl.
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ANTIVIRAL BETA-AMINO ACID ESTER PHOSPHODIAMIDE COMPOUNDS (Fri, 17 Feb 2017)
Compounds of Formula (I) and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
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NOVEL C28-AMIDES WITH C3-MODIFICATIONS OF TRITERPENE DERIVATIVES AS HIV INHIBITORS (Fri, 17 Feb 2017)
Formula (I) The present invention relates to novel C28-amides with C3-modifications of triterpene compounds of formula (I); or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, prodrugs or combination thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, X, and Y are as defined herein. The present invention also relates to pharmaceutical compositions comprising compounds of formula (I) useful for the therapeutic treatment of viral mediated diseases and particularly HIV mediated diseases.
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NOVEL C28-ANALOGUES WITH C3-MODIFICATIONS OF TRITERPENE DERIVATIVES AS HIV INHIBITORS (Fri, 17 Feb 2017)
The present invention relates to compounds of novel C28-analogues with C3- modifications of triterpene derivatives of formula (I); or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, and Z are as defined herein. The present invention also relates to pharmaceutical compositions comprising compounds of formula (I) useful for the treatment of viral diseases and particularly HIV mediated diseases.
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Pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication (Fri, 17 Feb 2017)
Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
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5-(n-[6,5]-fused bicyclic aryl tetrahydroisoquinolin-6-yl) pyridin-3-yl acetic acid derivatives as inhibitors of human immunodeficiency virus replication (Fri, 17 Feb 2017)
Disclosed are compounds of Formula (I), including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.
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Benzothiazol-6-yl acetic acid derivatives and their use for treating an HIV infection (Fri, 17 Feb 2017)
Compounds disclosed herein including compounds of formula (I') and salts thereof are provided. Pharmaceutical compositions comprising compounds disclosed herein, processes for preparing compounds disclosed herein, intermediates useful for preparing compounds disclosed herein and therapeutic methods for treating an HIV infection using compounds disclosed herein are also provided.
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Antiviral beta-amino acid ester phosphodiamide compounds (Fri, 17 Feb 2017)
Compounds of Formula (I) and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
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ANTIVIRAL 4-(2-AMINO-6-HETEROCYLYL-9H-PURIN-9-YL)-2-CYCLOPENTENE-1 -METHANOL COMPOUNDS (Fri, 10 Feb 2017)
The present invention relates to certain antiviral compounds of formula I as defined herein that function as nucleoside reverse transcriptase inhibitors. The present invention also relates to processes for the preparation of these compounds, pharmaceutical compositions comprising them and to their use for the treatment of retroviral infections, and in particular their use in the treatment of HIV-1 virus.
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NOVEL SUBSTITUTED AMIDES OF TRITERPENE DERIVATIVES AS HIV INHIBITORS (Fri, 10 Feb 2017)
The present invention relates to compounds of novel substituted amides of triteripene derivatives of formula (I); or pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, tautomers, stereoisomers, prodrugs, compositions or combination thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y, Z1, Z2, Z3 and formula (II) are as defined herein. The present invention also relates to,, and pharmaceutical compositions comprising compounds of formula (I) useful for the treatment of viral diseases and particularly HIV mediated diseases.
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PROCESS FOR PREPARING COMPOUND HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Thu, 09 Feb 2017)
A process for preparing a compound represented by formula (Y1) or (Y2) [wherein R x is an optionally substituted carbocyclyl lower alkyl, or the like] or a salt thereof, using a novel process for preparing a pyridone derivative represented by formula (X4) [wherein R 1d is hydrogen, halogen, or the like; R 2d is hydrogen, a lower alkyl optionally substituted with substituent E, or the like; R 4d is a lower alkyl optionally substituted with substituent E, or the like; and R 6d is a lower alkyl group optionally substituted with substituent group E].
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 03 Feb 2017)
<p id="p-0001" num="0000">The present invention is to provide a novel compound (I) shown below, having the anti-virus activity, particularly the HIV integrase inhibitory activity, and a drug containing the same, particularly an anti-HIV drug, as well as a process and an intermediate thereof.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.35mm" wi="60.45mm" file="US20170029438A1-20170202-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">(wherein <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">Z<sup>1 </sup>is NR<sup>4</sup>;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is hydrogen or lower alkyl;</li> <li id="ul0002-0003" num="0000">X is a single bond, a hetero atom group selected from O, S, SO, SO<sub>2 </sub>and NH, or lower alkylene or lower alkenylene in which the hetero atom group may intervene;</li> <li id="ul0002-0004" num="0000">R<sup>2 </sup>is optionally substituted aryl;</li> <li id="ul0002-0005" num="0000">R<sup>3 </sup>is hydrogen, a halogen, hydroxy, optionally substituted lower alkyl etc; and</li> <li id="ul0002-0006" num="0000">R<sup>4 </sup>and Z<sup>2 </sup>part taken together forms a ring, to form a polycyclic compound, including e.g., a tricyclic or tetracyclic compound.</li> </ul> </li> </ul> </p>
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BETUIN DERIVATIVES FOR PREVENTING OR TREATING HIV INFECTIONS (Fri, 03 Feb 2017)
The present invention relates to compounds characterized by having a structure according to the following Formula I, or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
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BETUIN DERIVATIVES FOR PREVENTING OR TREATING HIV INFECTIONS (Fri, 03 Feb 2017)
The present invention relates to compounds characterized by having a structure according to the following Formula (I), or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
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NOVEL BETULINIC SUBSTITUTED AMIDE DERIVATIVES AS HIV INHIBITORS (Fri, 03 Feb 2017)
The present invention relates to novel betulinic substituted amide compounds of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y, Z1, Z2, Z3 and are Formula (II) as defined herein. The invention novel betulinic substituted amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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Modulators of toll-like receptors for the treatment of HIV (Fri, 03 Feb 2017)
Provided are methods, uses, pharmaceutical regimens, pharmaceutical compositions, and kits comprising modulators of TLR7, including those of Formula (II); and pharmaceutically acceptable salts thereof, useful in treating HIV infections.
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Betuin derivatives for preventing or treating HIV infections (Fri, 03 Feb 2017)
The present invention relates to compounds characterized by having a structure according to the following Formula (I), or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
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Betuin derivatives for preventing or treating HIV infections (Fri, 03 Feb 2017)
The present invention relates to compounds characterized by having a structure according to the following Formula I, or a pharmaceutically acceptable salt thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.
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Methods for inhibiting HIV-1 activity by inhibitory mechanisms of extracts of <i>Guaiacum officinale </i>L. (zygophyllaceae) (Fri, 27 Jan 2017)
<p id="p-0001" num="0000">A therapeutic phenolic extract derived from plant biomass, and more specifically the indigenous Jamaican plant <i>guaiacum officinale </i>L. (Zygophyllaceae), for use in regressing or controlling HIV-1 replication in infected patients, and to help prevent sexual transmission of HIV-1, as well as the method for inhibiting HIV-1 by administering a pharmaceutically-acceptable amount of the crude extract to prevent HIV-viral replication without causing excessive damage to normal cells.</p>
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Imidazopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.48mm" wi="46.57mm" file="US09932353-20180403-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Pyrazolopyrimidine macrocycles as inhibitors of human immunodeficiency virus replication (Fri, 20 Jan 2017)
<p id="p-0001" num="0000">The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.69mm" wi="46.99mm" file="US09932356-20180403-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Phenyl and tertbutylacetic acid substituted pyridinones having anti-HIV effects (Fri, 20 Jan 2017)
Compounds of Formula I are disclosed and methods of treating viral invections with compositions comprising such compounds. Formula I
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PYRIDIN-3-YL ACETIC ACID MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Thu, 19 Jan 2017)
The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.
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Inhibitors of human immunodeficiency virus replication (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="99.57mm" wi="60.88mm" file="US09938271-20180410-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Benzothiazole macrocycles as inhibitors of human immunodeficiency virus replication (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.14mm" wi="46.91mm" file="US09944656-20180417-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PYRAZOLOPYRIMIDINE MACROCYCLES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.26mm" wi="46.99mm" file="US20170008909A1-20170112-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Pyridin-3-yl acetic acid macrocycles as inhibitors of human immunodeficiency virus replication (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="26.33mm" wi="56.64mm" file="US09637501-20170502-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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C-3 NOVEL TRITERPENONE WITH C-28 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS (Fri, 13 Jan 2017)
<p id="p-0001" num="0000">The invention relates to C-3 novel triterpenone with C-28 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.15mm" wi="75.78mm" file="US20170008921A1-20170112-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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1−(3−アミノプロピル)置換環状アミン系化合物、その製造方法、薬物組成物および使用 (Fri, 13 Jan 2017)
<p num="">一般式(I)で表される1-(3-アミノプロピル)置換環状アミン系化合物とその薬学的に許容される塩、エナンチオマー、ジアステレオマー、ラセミ体およびこれらの混合物、ならびに芳香族複素環カルボキシアルデヒドを原料として前記1-(3-アミノプロピル)置換環状アミン系化合物を合成する方法を提供する。前記化合物は、CCR5拮抗剤として、HIV感染の治療に使用することができる。</p>
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