HIV

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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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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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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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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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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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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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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METHODS OF PRODUCING COMPOUNDS HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 25 Aug 2017)
<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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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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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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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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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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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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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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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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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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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="US20170217890A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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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="US20170217986A1-20170803-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </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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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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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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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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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="US20170204133A1-20170720-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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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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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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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)
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 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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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="US20170173015A1-20170622-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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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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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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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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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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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="US20170137405A1-20170518-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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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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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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NOVEL 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="US20170129917A1-20170511-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, 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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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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POLYCYCLICCARBAMOYLPYRIDONE 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="US20170119764A1-20170504-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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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="US20170107234A1-20170420-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">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>4</sup>C, 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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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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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="24.89mm" wi="42.84mm" file="US20170088554A1-20170330-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or a salt thereof as described herein. The invention also provided 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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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="42.67mm" wi="69.00mm" file="US20170088555A1-20170330-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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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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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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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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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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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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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="US20170057977A1-20170302-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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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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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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="US20170044192A1-20170216-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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AMYLOID Precursor Protein (APP) Based β-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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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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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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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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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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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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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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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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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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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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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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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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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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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 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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METHODS FOR INHIBITING HIV-1 ACTIVITY BY INHIBITORY MECHANISMS OF EXTRACTS OF GUAIACUM OFFICINALE 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="US20170015681A1-20170119-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="US20170015683A1-20170119-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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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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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="US20170008912A1-20170112-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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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="100.16mm" wi="60.88mm" file="US20170008887A1-20170112-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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USE OF TREM-1 INHIBITORS FOR TREATMENT, ELIMINATION AND ERADICATION OF HIV-1 INFECTION (Fri, 13 Jan 2017)
Compounds, compositions, and methods of treatment and prevention of HIV, including HIV-1 and HIV-2, Dengue, and Chikungunya infection are disclosed. The compounds are TREM-1 inhibitors. Combinations of these TREM-1 inhibitors and additional antiretroviral compounds, such as NRTI, NNRTI, integrase inhibitors, entry inhibitors, protease inhibitors, JAK inhibitors, macrophage depleting agents, 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, Dengue, or Chikungunya virus in an infected patient.
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ANTIVIRAL PHOSPHODIAMIDE COMPOUNDS (Fri, 13 Jan 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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PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 13 Jan 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, 13 Jan 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, 13 Jan 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, 13 Jan 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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BIOMARKERS (Fri, 06 Jan 2017)
<p id="p-0001" num="0000">The invention relates to biomarkers for diagnosing, monitoring and/or treating <i>tuberculosis </i>in both immunocompetent and immunocompromised individuals with or without co-infection with HIV, monitoring the responses of individuals to anti-myco-bacterial chemotherapy, monitoring the progression of latent <i>tuberculosis </i>to active <i>tuberculosis</i>, differentiating active <i>tuberculosis </i>from latent <i>tuberculosis</i>, and from other clinical conditions that mimic <i>tuberculosis </i>(TB). The invention also relates to methods for diagnosing, monitoring and/or treating <i>tuberculosis </i>using said biomarkers. The above pertain in all aspects both to pulmonary and extrapulmonary <i>Mycobacterium tuberculosis </i>infections, with <i>Mycobacterium tuberculosis </i>being the causative organism in <i>tuberculosis</i>. The invention therefore finds great utility in assisting with future drug discovery efforts for <i>tuberculosis </i>and also provides proxy clinical end points as well as being an effective predictor of a response to treatment.</p>
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INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE (Fri, 06 Jan 2017)
Provided are compounds of formula (I) 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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COMPOUNDS AND THEIR USE AS INHIBITORS OF N-MYRISTOYL TRANSFERASE (Fri, 06 Jan 2017)
This invention provides compounds of formula (I) and salts thereof, which have activity as inhibitors of N-myristoyl transferase (NMT). The invention also relates to uses of such compounds as medicaments, in particular in the treatment of a disease or disorder in which inhibition of N-myristoyl transferase provides a therapeutic or prophylactic effect, including protozoan infections (such as malaria and leishmaniasis), viral infections (such as human rhinovirus and HIV), and hyperproliferative disorders (such as B-cell lymphoma).
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Immunogenic polypeptides comprising a modified loop peptide presenting the HIV-1 GP120 3074 mAb epitope and scaffold proteins containing said peptide (Wed, 04 Jan 2017)
<p id="p-0001" num="0000">The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.</p>
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TREATMENT OF INFECTIOUS DISEASES WITH GLUCOSE UPTAKE INHIBITORS (Fri, 30 Dec 2016)
Provided are methods of treating infectious diseases in mammals comprising administering a compound that inhibits glucose uptake. Particular infectious diseases that may be treated include malaria, leishmaniasis, African trypanosomiasis, tuberculosis, HIV, HCMV or herpes virus. In a first aspect, the invention features a method of treating infectious diseases in a mammal, comprising administering to a mammalian subject in need thereof a therapeutically effective amount of a compound or prodrug thereof, or pharmaceutically acceptable salt or ester of said compound or prodrug, wherein the compound is an inhibitor of glucose uptake.
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THERAPEUTIC COMPOUNDS (Fri, 23 Dec 2016)
<p id="p-0001" num="0000">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 Retroviridae viral infection, in particular 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="22.18mm" wi="63.16mm" file="US20160368881A1-20161222-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 (Thu, 22 Dec 2016)
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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SALTS OF PRODRUGS OF PIPERAZINE AND SUBSTITUTED PIPERIDINE ANTIVIRAL AGENTS (Fri, 16 Dec 2016)
<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="69.93mm" file="US20160361328A1-20161215-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein: <br/> X is C or N with the proviso that when X is N, R<sup>1 </sup>does not exist; <br/> W is C or N with the proviso that when W is N, R<sup>2 </sup>does not exist; <br/> V is C; <br/> E is hydrogen or a pharmaceutically acceptable salt thereof; and <br/> Y is selected from the group consisting of </p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="22.61mm" wi="63.25mm" file="US20160361328A1-20161215-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I.</p> <p id="p-0006" num="0000"><chemistry id="CHEM-US-00003" num="00003"> <img id="EMI-C00003" he="36.24mm" wi="69.93mm" file="US20160361328A1-20161215-C00003.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0007" num="0000">wherein: <br/> 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. </p>
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CARBOHYDRATE-LIPID CONSTRUCTS AND THEIR USE IN PREVENTING OR TREATING VIRAL INFECTION (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The invention relates to selected carbohydrate-lipid constructs and their use as mimics of ligands for receptors expressed by a virus. In particular, the invention relates to the use of selected carbohydrate-lipid constructs in methods of inhibiting virus infection and/or promoting clearance of virus from infected subjects. Carbohydrate-lipid constructs selected for use in these methods where the virus is Human Immunodeficiency Virus (HIV) are provided.</p>
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CD4-MIMETIC SMALL MOLECULES SENSITIZE HUMAN IMMUNODEFICIENCY VIRUS TO VACCINE-ELICITED ANTIBODIES (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">Described herein are methods of generating a protein binding domain that specifically binds to gp120 in a specific conformational state, comprising contacting gp120 with a CD4-mimetic compound, thereby forming gp120 in the specific conformational state; and generating antibodies to gp120 in the specific conformation state. Relatedly, the disclosure also describes methods of neutralizing HIV-1, comprising contacting HIV-1 with an effective amount of a CD4-mimetic compound, thereby forming HIV-1 having gp120 in a specific conformational state; and contacting the HIV-1 in the specific conformational state with an antibody.</p>
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PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE (Fri, 16 Dec 2016)
<p id="p-0001" num="0000">The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds (referred to herein as “PPDA compounds”) that, inter alia, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.</p>
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HIV INHIBITING BICYCLIC PYRIMIDINE DERIVATIVES (Fri, 09 Dec 2016)
<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="38.18mm" wi="69.85mm" file="US20160355519A1-20161208-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"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" 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="ul0002-0002" num="0000">n and m is 0, 1, 2, 3 and in certain cases also 4;</li> <li id="ul0002-0003" 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="ul0002-0004" 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="ul0002-0005" 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="ul0002-0006" 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="ul0002-0007" 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="ul0002-0008" 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> </li> </ul> </p>
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INHIBITORS OF HIV REPLICATION (Fri, 09 Dec 2016)
<p id="p-0001" num="0000">The present invention relates to novel 2,3,4-substituted 5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridine compounds and pharmaceutically acceptable salts thereof, to compositions containing such compounds and to the use of such compounds as inhibitors of HIV replication.</p>
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Salts of HIV inhibitor compounds (Fri, 09 Dec 2016)
<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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SOLID FORMS OF TENOFOVIR ALAFENAMIDE (Fri, 09 Dec 2016)
The invention relates to a solid form of tenofovir alafenamide with an inorganic or organic acid selected from the following group: hydrochloric, hydrobromic, sulfuric, phosphoric, maleic, citric, succinic, tartaric, gallic, benzenesulfonic, salicylic, 4- aminobenzoic acid. Another aspect of the present invention provides a pharmaceutical composition, which comprises the solid form of tenofovir alafenamide and at least one pharmaceutically acceptable excipient, the composition being used as a medicament for the treatment of HIV infection and viral hepatitis B. (I)
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Polycyclic-carbamoylpyridone compounds and their pharmaceutical use (Fri, 09 Dec 2016)
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 R1, X, W, Yi, Y2, Zi and Z4 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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Amide compounds for the treatment of HIV (Fri, 09 Dec 2016)
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 Retroviridae viral infection including an infection caused by the HIV virus.
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UREA DERIVATIVE OR PHARMACOLOGICALLY ACCEPTABLE SALT THEREOF (Fri, 02 Dec 2016)
The present invention provides a urea derivative or a pharmacologically acceptable salt thereof that has a formyl peptide receptor like 1 (hereinafter may be abbreviated as FPRL1) agonist effect, a pharmaceutical composition containing the urea derivative or the pharmacologically acceptable salt thereof, and a pharmaceutical use thereof. It has been found that a urea derivative represented by the general formula (I) below or a pharmacologically acceptable salt thereof has a superior FPRL1 agonist effect. Compound (I) or a pharmacologically acceptable salt thereof is highly useful for treatment, prevention, or suppression of inflammatory diseases, chronic airway diseases, cancers, septicemia, allergic symptoms, HIV retrovirus infection, circulatory disorders, neuroinflammation, nervous disorders, pains, prion diseases, amyloidosis, immune disorders and the like.
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UREA DERIVATIVE OR PHARMACOLOGICALLY ACCEPTABLE SALT THEREOF (Fri, 02 Dec 2016)
The present invention provides a urea compound or a pharmacologically acceptable salt thereof that has a formyl peptide receptor like 1 (hereinafter may be abbreviated as FPRL1) agonist effect, a pharmaceutical composition containing the urea compound or the pharmacologically acceptable salt thereof, and a pharmaceutical use thereof. It has been found that a urea derivative represented by the general formula (I) below or a pharmacologically acceptable salt thereof has a superior FPRL1 agonist effect. Compound (I) or a pharmacologically acceptable salt thereof is highly useful for treatment, prevention, or suppression of inflammatory diseases, chronic airway diseases, cancers, septicemia, allergic symptoms, HIV retrovirus infection, circulatory disorders, neuroinflammation, nervous disorders, pains, prion diseases, amyloidosis, immune disorders and the like.
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FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS USEFUL FOR TREATING HIV INFECTION (Fri, 02 Dec 2016)
The present invention relates to Fused Tricyclic Heterocycle Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, Y, m, R1, R2, R3, R3, R3, R4, R5 and R9 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.
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FUSED TRICYCLIC HETEROCYCLIC COMPOUNDS USEFUL FOR TREATING HIV INFECTION (Fri, 02 Dec 2016)
Fused tricyclic heterocycle derivatives of formula (I) and pharmaceutically acceptable salts thereof, 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 are provided.
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3-(6-CHLORO-3-OXO-3,4-DIHYDRO-(2H)-1,4-BENZOXAZIN-4-YL) PROPANOIC ACID DERIVATIVES AND THEIR USE AS KMO INHIBITORS (Fri, 02 Dec 2016)
Compounds of formula (I) wherein: R1 is heteroaryl optionally substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl. and salts thereof are KMO inhibitors and may be useful in the treatment of various disorders, for example acute pancreatitis, chronic kidney disease, 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.
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3-(5-CHLORO-2-OXO-2,3-DIHYDRO-1,3-BENZOTHIAZOL-3-YL) PROPANOIC ACID DERIVATIVES AND THEIR USE AS KMO INHIBITORS (Fri, 02 Dec 2016)
Compounds of formula (I) wherein: R1 is heteroaryl optionally substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl. 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.
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Processes and intermediates for preparing anti-HIV agents (Fri, 25 Nov 2016)
<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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Compounds and method for treatment of HIV (Fri, 18 Nov 2016)
<p id="p-0001" num="0000">The invention relates to a compound of Formulae I and/or II:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="57.66mm" wi="59.18mm" file="US09624220-20170418-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and/or 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<sub>2</sub>, 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. </p>
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FUNCTIONAL CURE OF RETROVIRAL INFECTION (Fri, 18 Nov 2016)
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.
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C-3 NOVEL TRITERPENONE WITH C-28 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS (Fri, 11 Nov 2016)
Formula (I) 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.
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ISOFORM-SELECTIVE LYSINE DEACETYLASE INHIBITORS (Fri, 11 Nov 2016)
Isoform-selective lysine deacetylase inhibitors are described. Inhibitors of the lysine deacetylase enzyme are useful as antitumor drugs and for treating addiction, asthma, cardio-vascular disease, immunosuppression, neurodegenerative diseases, sepsis, sickle-cell disease, uveal melanoma and termination of viral latency, particularly HIV-1 latency.
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C-3 novel triterpenone with C-28 reverse amide derivatives as HIV inhibitors (Fri, 11 Nov 2016)
Formula (I) 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.
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1-(3-AMINOPROPYL) SUBSTITUTED CYCLIC AMINE COMPOUNDS, PREPARATION METHOD THEREFOR, AND PHARMACEUTICAL COMPOSITIONS AND USES THEREOF (Thu, 10 Nov 2016)
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.
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Spirocyclic hetercycle compounds useful as HIV integrase inhibitors (Fri, 04 Nov 2016)
<p id="p-0001" num="0000">The present invention relates to Spirocyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, Y, R<sup>1</sup>, R<sup>2 </sup>and R<sup>11 </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="29.38mm" wi="69.68mm" file="US09707234-20170718-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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NOVEL DRUG TARGET SITE WITHIN GP120 OF HIV (Fri, 28 Oct 2016)
<p id="p-0001" num="0000">The present invention relates to a method of designing an inhibitor of the binding of HIV (human immunodeficiency virus) glycoprotein (gp)120 to a CD4-receptor or to the integrin alpha4 beta7 (a4b7). The inhibitor interacts with at least two amino acid residues comprised in six motifs within the 3-dimensional structure of gp120. Also provided are compounds, pharmaceutical compositions thereof and uses thereof in the development of an inhibitor of the binding of a HIV gp120 to a CD4-receptor or an integrin alpha4 beta7 (a4b7). The inhibitors are useful for the prevention or treatment of an HIV infection and/or diseases associated with an HIV infection.</p>
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HIV PROTEASE INHIBITORS (Fri, 28 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to 2,5,6-substituted morpholine derivatives 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. 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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INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 28 Oct 2016)
Compounds of Formula I, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth: (I)
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INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 28 Oct 2016)
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: Formula (i)
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Triterpenoids with HIV maturation inhibitory activity, substituted in position 3 by a non-aromatic ring carrying a haloalkyl substituent (Fri, 28 Oct 2016)
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: with X selected from C<sb>4-8</sb> cycloalkyl, C<sb>4-8</sb> cycloalkenyl, C<sb>4-9</sb> spirocycloalkyl, C<sb>4-9</sb> spirocycloalkenyl, C<sb>4-8</sb> oxacycloalkyl, C<sb>4-8</sb> dioxacycloalkyl, C<sb>6-8</sb> oxacycloalkenyl, C<sb>6-8</sb> dioxacycloalkenyl, C<sb>6</sb> cyclodialkenyl, C<sb>6</sb> oxacyclodialkenyl, C<sb>6-9</sb> oxaspirocycloalkyl and C<sb>6-9</sb> oxaspirocycloalkenyl ring, such that X is substituted with A, wherein A is -C<sb>1-6</sb> alkyl- halo. These compounds are useful for the treatment of HIV and AIDS.
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ANTIVIRAL JAK INHIBITORS USEFUL IN TREATING OR PREVENTING RETROVIRAL AND OTHER VIRAL INFECTIONS (Fri, 28 Oct 2016)
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. FIG. 1 Potency and toxicity of Tofacitinib or Jakafi versus FDA approved controls AZT and 3TC CONDENThAL Figure 1
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 21 Oct 2016)
<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="US20160304535A1-20161020-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>1</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 forma polycyclic compound, including e.g., a tricyclic or tetracyclic compound.</li> </ul> </li> </ul> </p>
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Benzothiazole compounds and their pharmaceutical use (Fri, 21 Oct 2016)
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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Process for making reverse transcriptase inhibitors (Fri, 14 Oct 2016)
<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 and HIV replication, and the treatment of human immunodeficiency virus infection in humans.</p>
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HIV protease inhibitors (Fri, 14 Oct 2016)
<p id="p-0001" num="0000">The present invention is directed to 5-heteroarylmorpholine derivatives 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. 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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Polycyclic-carbamoylpyridone compounds and their pharmaceutical use (Fri, 07 Oct 2016)
<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="63.75mm" file="US09630978-20170425-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> including stereoisomers and pharmaceutically acceptable salts thereof, wherein A, A′, R<sup>1 </sup>and R<sup>2 </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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POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE (Fri, 07 Oct 2016)
Compounds for use in the treatment of human immunodeficiency (HIV) infection are disclosed. The compounds have the following Formula (la): including stereoisomers and pharmaceutically acceptable salts thereof, wherein A, A', R1 and R2 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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Swarm immunization with envelopes from CH505 (Fri, 07 Oct 2016)
In certain aspects the invention provides HIV-1 immunogens, including envelopes (CH505) and selections therefrom, and methods for swarm immunizations using combinations of HIV-1 envelopes.
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Pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds as CDK inhibitors and their therapeutic use (Fri, 07 Oct 2016)
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7- diamine compounds (referred to herein as "PPDA compounds") that, <i>inter alia</i>, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.
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4'-substituted nucleoside-derivatives as HIV reverse transcriptase inhibitors (Fri, 07 Oct 2016)
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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Prodrugs of HIV reverse transcriptase inhibitors (Fri, 07 Oct 2016)
Compounds of Formula I are described: wherein R<sp>1 </sp>and R<sp>2</sp> 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.
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2′,4′-substituted nucleosides as antiviral agents (Fri, 30 Sep 2016)
<p id="p-0001" num="0000">Embodiments of the invention are to compounds, methods, and compositions for use in the treatment of viral infections. More specifically embodiments of the invention are 2′,4′-substituted nucleoside compounds useful for the treatment of viral infections, such as HIV, HCV, and HBV infections.</p>
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PHOSPHATE-SUBSTITUTED QUINOLIZINE DERIVATIVES USEFUL AS HIV INTEGRASE INHIBITORS (Fri, 30 Sep 2016)
The present invention relates to Phosphate Substituted Quinolizine Derivatives of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, R1, R2, R3, R4, R5, R9 and R10 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.
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NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 23 Sep 2016)
<p id="p-0001" num="0000">A compound of Formula I is provided:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="43.01mm" wi="56.98mm" file="US20160272628A1-20160922-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or pharmaceutically acceptable enantiomers, salts or solvates thereof. The invention further relates to the use of the compounds of Formula I as TDO2 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.</p>
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C-3 NOVEL TRITERPENONE WITH C-28 AMIDE DERIVATIVES AS HIV INHIBITORS (Fri, 23 Sep 2016)
The invention relates to C-3 novel triterpenone with C-28 amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases (formula 1).
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NOVEL 3-INDOL SUBSTITUTED DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 23 Sep 2016)
A compound of Formula I is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The 5 invention further relates to the use of the compounds of Formula I as TDO2 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 10 relates to a process for manufacturing compounds of Formula I.
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Novel 3-indol substituted derivatives, pharmaceutical compositions and methods for use (Fri, 23 Sep 2016)
A compound of Formula I is provided: or pharmaceutically acceptable enantiomers, salts or solvates thereof. The 5 invention further relates to the use of the compounds of Formula I as TDO2 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 10 relates to a process for manufacturing compounds of Formula I.
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BENZOTHIAZOL-6-YL ACETIC ACID DERIVATIVES AND THEIR USE FOR TREATING AN HIV INFECTION (Thu, 22 Sep 2016)
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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BROADLY NEUTRALIZING HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 (HIV-1) GP120-SPECIFIC MONOCLONAL ANTIBODY (Fri, 16 Sep 2016)
<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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NOVEL 4-(INDOL-3-YL)-PYRAZOLE DERIVATIVES, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR USE (Fri, 16 Sep 2016)
<p id="p-0001" num="0000">4-(Indol-3-yl)-pyrazole derivative compounds of Formula I or pharmaceutically acceptable enantiomers, salts or solvates thereof are provided. Further provided is the use of the compounds of Formula I as TDO2 inhibitors. Also provided herein is 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.</p>
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POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE (Thu, 15 Sep 2016)
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, W, Y 1 , Y 2 , Z 1 and Z 4 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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4-AMINO-3-PHENYLAMINO-6-PHENYLPYRAZOLO[3,4-D]PYRIMIDINE DERIVATIVES FOR USE AS BCRP INHIBITORS IN THERAPEUTIC TREATMENTS (Sat, 10 Sep 2016)
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 RH, which has a Hammett constant σp greater than 0.23. For corresponding compounds, surprisingly a particularly high inhibitory activity against BCRP has been discovered which can be exploited for supressing the multidrug resistance modulator BCRP, thus providing an improvement in efficacy of BCRP affected drugs. This has useful implications for cancer and HIV treatment.
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METHODS AND PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF HIV INFECTION (Sat, 10 Sep 2016)
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:
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3-HYDROXYPYRIMIDINE-2,4-DIONE-5-CARBOXAMIDES AS POTENT INHIBITORS OF HIV (Sat, 10 Sep 2016)
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 aginst 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.
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4-amino-3-phenylamino-6-phenylpyrazolo[3,4-d]pyrimidine derivatives for use as BCRP inhibitors in therapeutic treatments (Sat, 10 Sep 2016)
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<sp>H</sp>, which has a Hammett constant σ<sb>p</sb> greater than 0.23. For corresponding compounds, surprisingly a particularly high inhibitory activity against BCRP has been discovered which can be exploited for supressing the multidrug resistance modulator BCRP, thus providing an improvement in efficacy of BCRP affected drugs. This has useful implications for cancer and HIV treatment.
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PEPTIDE INHIBITOR OF HIV REVERSE TRANSCRIPTION (Fri, 09 Sep 2016)
<p id="p-0001" num="0000">Disclosed are peptides that exhibit good binding to the anticodon stem and loop (ASL) of human lysine tRNA species, tRNA<sup>Lys3</sup>. Using a search algorithm combining Monte Carlo (MC) and self-consistent mean field (SCMF) techniques, the peptides were evolved a with the ultimate purpose of using them to break the replication cycle of HIV-1 virus. The starting point was the 15-amino-acid sequence, RVTHHAFLGAHRTVG, found experimentally to bind selectively to hypermodified tRNA<sup>Lys3</sup>. The peptide backbone conformation was determined via atomistic simulation of the peptide-ASL<sup>Lys3 </sup>complex and then held fixed throughout the search. The proportion of amino acids of various types (hydrophobic, polar, charged, etc.) was varied to mimic different peptide hydration properties. Three different sets of hydration properties were examined in the search algorithm to see how this affects evolution to the best-binding peptide sequences. Certain amino acids are commonly found at fixed sites for all three hydration states, some necessary for binding affinity and some necessary for binding specificity. Analysis of the binding structure and the various contributions to the binding energy shows that: 1) two hydrophilic residues (asparagine (ASN) at site 11 and the cysteine (CYS) at site 12) “recognize” the ASL<sup>Lys3 </sup>due to the VDW energy, and thereby contribute to its binding specificity, and 2) the positively-charged arginines (ARG) at sites 4 and 13 preferentially attract the negatively-charged sugar rings and the phosphate linkages, and thereby contribute to the binding affinity.</p>
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INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 09 Sep 2016)
<p id="p-0001" num="0000">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)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.44mm" wi="55.88mm" file="US20160257645A1-20160908-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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4-amino-3-phenylamino-6-phenylpyrazolo[3,4-d]pyrimidine derivatives for use as BCRP inhibitors in therapeutic treatments (Thu, 08 Sep 2016)
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 H , which has a Hammett constant à p greater than 0.23. For corresponding compounds, surprisingly a particularly high inhibitory activity against BCRP has been discovered which can be exploited for supressing the multidrug resistance modulator BCRP, thus providing an improvement in efficacy of BCRP affected drugs. This has useful implications for cancer and HIV treatment.
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Methods of Making and Using Thioxothiazolidine and Rhodanine Derivatives as HIV-1 and JSP-1 Inhibitors (Fri, 02 Sep 2016)
<p id="p-0001" num="0000">The present invention provides methods of making and using 5-(2-(indol-3-yl)-2-oxoethylidene)-3-phenyl-2-thioxothiazolidin-4-one derivatives having HIV-1 or JSP-1 inhibitory activity.</p>
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A NEW QUINOLINE DERIVATIVE FOR USE IN THE TREATMENT AND PREVENTION OF VIRAL INFECTIONS (Fri, 02 Sep 2016)
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.
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Replicating recombinant adenovirus vectors, compositions, and methods of use thereof (Fri, 02 Sep 2016)
Replicating recombinant adenovirus vectors derived from human adenovirus serotype 26 or human adenovirus serotype 35 are described. The replicating recombinant adenovirus vectors have attenuated replicative capacity as compared to that of the corresponding wild-type adenovirus. They can be used for stable expression of heterologous genes <i>in vivo</i>. Also described are compositions and methods of using these recombinant adenovirus vectors to induce an immune response in a subject, and vaccinate a subject against an immunogenic human immunodeficiency virus (HIV) infection.
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A new quinoline derivative for use in the treatment and prevention of viral infections (Fri, 02 Sep 2016)
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.
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A new quinoline derivative for use in the treatment and prevention of viral infections (Thu, 25 Aug 2016)
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 use as a 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.
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COMPOUNDS THAT BIND TO HUMAN IMMUNODEFICIENCY VIRUS REV RESPONSE ELEMENT (Fri, 19 Aug 2016)
<p id="p-0001" num="0000">Disclosed herein are compounds (such as peptides or peptide mimetics) that bind to HIV RRE RNA. In some examples, the compounds inhibit (for example, decrease) binding of Rev to the RRE RNA. In some embodiments, the compounds include two moieties, each of which bind to one of the Rev binding sites in the RRE. In some examples, the moieties include peptides or small molecules. In some examples, the peptides include an arginine-rich motif. The RRE binding compounds may be further linked to a detectable label or cargo moiety. Also disclosed are methods of treating or inhibiting HIV including administering one or more of the disclosed compounds to a subject.</p>
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Processes and intermediates for preparing anti-HIV agents (Fri, 12 Aug 2016)
The invention provides synthetic processes and synthetic intermediates that can be used to prepare compounds having useful anti-HIV properties.
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Mutagenic nucleoside analogs and uses thereof (Fri, 05 Aug 2016)
<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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MUTAGENIC NUCLEOSIDE ANALOGS AND USES THEREOF (Fri, 05 Aug 2016)
The present disclosure provides nucleoside analogs of Formula (I) or (II). The nucleoside analogs may 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 pKa (e.g., to a pKa 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.
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LOWCOST, HIGH YIELD SYNTHESIS OF NEVIRAPINE (Fri, 29 Jul 2016)
Improved methods of producing the HIV drug substance, nevirapine are provided. The methods employ a cost effective and high yield synthetic methods for preparing the nevirapine building block 2-chloro-3-amino-4-picoline (CAPIC) and 2-cyclopropyl amino nicotinate (Me-CAN), and improvements in other steps of nevirapine synthesis.
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SUBSTITUTED AZAINDOLEOXOACETIC PIPERAZINE DERIVATIVES WITH PROTEASE INHIBITORS (Fri, 22 Jul 2016)
<p id="p-0001" num="0000">This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives having the Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="15.32mm" wi="50.12mm" file="US20160207918A1-20160721-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein Q is</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="26.67mm" wi="32.68mm" file="US20160207918A1-20160721-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.</p>
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POLYCYCLIC CARBAMOYLPYRIDONE DERIVATIVE HAVING HIV INTEGRASE INHIBITORY ACTIVITY (Fri, 22 Jul 2016)
<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="US20160207939A1-20160721-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 (Thu, 21 Jul 2016)
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 COMPOUNDS AND THEIR PHARMACEUTICAL USE (Fri, 08 Jul 2016)
<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="US20160194335A1-20160707-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>, Z<sup>2</sup>, or 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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POLYCYCLIC-CARBAMOYLPYRIDONE COMPOUNDS AND THEIR PHARMACEUTICAL USE (Fri, 01 Jul 2016)
Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (la): (la) including stereoisomers and pharmaceutically acceptable salts thereof, wherein A', R1, R2 and R3 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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FUSED PYRIMIDINE COMPOUNDS FOR THE TREATMENT OF HIV (Fri, 01 Jul 2016)
Described herein are compounds of Formula (I) and tautomers and pharmaceutical salts thereof, compositions and formulations containing such compounds, and methods of using and making such compounds.
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CO-CRYSTALS OF 5-AMINO-2-OXOTHIAZOLO[4,5-D]PYRIMIDIN-3(2H)-YL-5-HYDROXYMETHYL TETRAHYDROFURAN-3-YL ACETATE AND METHODS FOR PREPARING AND USING THE SAME (Fri, 01 Jul 2016)
Co-crystals of Formula I compounds and their pharmaceutical compositions are novel therapeutics for the treatment of diseases, such as human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection and cancer. The co-crystal are more stable to oxidation and aqueous degradation, have a better pharmacokinetic profile and superior biological activity than the corresponding tosylate salt form of Formula I compound. (Formula I)
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ISOQUINOLINE COMPOUNDS FOR THE TREATMENT OF HIV (Fri, 01 Jul 2016)
Described herein are compounds of Formula (I) and tautomers and pharmaceutical salts thereof, compositions and formulations containing such compounds, and methods of using and making such compounds.
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QUINAZOLINE DERIVATIVES USED TO TREAT HIV (Fri, 01 Jul 2016)
Described herein are compounds of Formula (I) and tautomers and pharmaceutical salts thereof, compositions and formulations containing such compounds, and methods of using and making such compounds.
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Quinazoline derivatives used to treat HIV (Fri, 01 Jul 2016)
Described herein are compounds of Formula (I) and tautomers and pharmaceutical salts thereof, compositions and formulations containing such compounds, and methods of using and making such compounds.
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Fused pyrimidine compounds for the treatment of HIV (Fri, 01 Jul 2016)
Described herein are compounds of Formula (I) and tautomers and pharmaceutical salts thereof, compositions and formulations containing such compounds, and methods of using and making such compounds.
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Isoquinoline compounds for the treatment of HIV (Fri, 01 Jul 2016)
Described herein are compounds of Formula (I) and tautomers and pharmaceutical salts thereof, compositions and formulations containing such compounds, and methods of using and making such compounds.
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Polycyclic-carbamoylpyridone compounds and their pharmaceutical use (Fri, 01 Jul 2016)
Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (la): (la) including stereoisomers and pharmaceutically acceptable salts thereof, wherein A', R<sp>1</sp>, R<sp>2</sp> and R<sp>3</sp> 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 pharmaceutical use (Fri, 24 Jun 2016)
<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="27.35mm" wi="63.84mm" file="US09522912-20161220-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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SUBSTITUTED 1,2,3,4,6,8,12,12a-OCTAHYDRO-1,4-METHANODIPYRIDO[1,2-a:1',2'-d]PYRAZINES AND METHODS FOR TREATING VIRAL INFECTIONS (Fri, 24 Jun 2016)
<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="US20160176885A1-20160623-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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Co-crystals of 5-amino-2-oxothiazolo[4,5-d]pyrimidin-3(2H)-yl-5-hydroxymethyl tetrahydrofuran-3-yl acetate and methods for preparing and using the same (Fri, 24 Jun 2016)
<p id="p-0001" num="0000">Co-crystals of Formula I compounds and their pharmaceutical compositions are novel therapeutics for the treatment of diseases, such as human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection and cancer. The co-crystal are more stable to oxidation and aqueous degradation, have a better pharmacokinetic profile and superior biological activity than the corresponding tosylate salt form of Formula I compound.</p>
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2-PHENETHENYLTETRAHYDRO ISOQUINOLINES USEFUL AS ANTI-HIV COMPOUNDS (Fri, 24 Jun 2016)
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.
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3-(6-ALKOXY-5-CHLOROBENZO[D]ISOXAZOL-3-YL)PROPANOIC ACID USEFUL AS KYNURENINE MONOOXYGENASE INHIBITORS (Fri, 24 Jun 2016)
Compound of formula (I) wherein R1 is heteroaryl either unsubstituted or substituted by methyl, ethyl, halo or =O; and R2 is H, methyl or ethyl; 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 disewase, 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.
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3-(6-alkoxy-5-chlorobenzo[d]isoxazol-3-yl)propanoic acid useful as kynurenine monooxygenase inhibitors (Fri, 24 Jun 2016)
Compound of formula (I) wherein R<sp>1</sp> is heteroaryl either unsubstituted or substituted by methyl, ethyl, halo or =O; and R<sp>2</sp> is H, methyl or ethyl; 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 disewase, 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.
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Oxone-Aceton Mediated Metal Free Preparation of Syn-Diols (Fri, 17 Jun 2016)
<p id="p-0001" num="0000">The present invention disclose a simple and high yielding process of Oxone-acetone mediated metal free syn-dihydroxylation of benzo fused olefins of formula (II) to obtain library of dioxolo compounds of formula (I). The invention further disclose a simple and high yielding process of Oxone-acetone mediated metal free syn-dihydroxylation of stilbene and its derivatives of formula (III) thereof. Also disclosed herein is Wacker-type oxidation of benzo-fused olefins of formula (X). The invention further disclose compounds of formula (I) which can be useful for the treatment of HIV, cancer or malaria.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.62mm" wi="54.86mm" file="US20160168114A1-20160616-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Anti-HIV compounds (Fri, 17 Jun 2016)
<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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SPIROCYCLIC HETEROCYCLE COMPOUNDS USEFUL AS HIV INTEGRATE INHIBITORS (Fri, 17 Jun 2016)
The present invention relates to Spirocyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, R1, R2, R3 and R4 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.
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SPIROCYCLIC HETEROCYCLE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS (Fri, 17 Jun 2016)
The present invention relates to Spirocyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, X, Y, R1, R2 and R4 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.
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SPIROCYCLIC HETEROCYCLE COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS (Fri, 17 Jun 2016)
The present invention relates to Spirocyclic Heterocycle Compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, B, X, R1, R2, R3 and R4 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.
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2' FLUORONUCLEOSIDES (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">2′-Fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="55.03mm" wi="56.13mm" file="US20160158266A1-20160609-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">Base is a purine or pyrimidine base;</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is OH, H, OR<sup>3</sup>, N<sub>3</sub>, CN, halogen, CF<sub>3</sub>, lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy;</li> <li id="ul0002-0003" num="0000">R<sup>2 </sup>is H, phosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving benzyl, a lipid, an amino acid, peptide, or cholesterol; and</li> <li id="ul0002-0004" num="0000">R<sup>3 </sup>is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group; or a pharmaceutically acceptable salt thereof.</li> </ul> </li> </ul> </p>
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PIPERAZINE DERIVATIVES AS HIV PROTEASE INHIBITORS (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention is directed to piperazine derivatives, 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>
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NOVEL UREIDO DERIVATIVES OF NAPHTHALENESULFONIC ACIDS (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">Objects of the present invention are novel ureido derivatives of naphthalensulfonic acids, pharmaceutical compositions comprising such derivatives, a process for the preparation thereof and the use of said derivatives as medications, in particular in the treatment of HIV infections. Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="60.03mm" wi="76.20mm" file="US20160159778A1-20160609-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Nucleoside and nucleotide derivatives (Fri, 10 Jun 2016)
<p id="p-0001" num="0000">The present invention discloses compounds of formula (I), 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="20.40mm" wi="58.00mm" file="US09732110-20170815-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> which inhibit, preventing or treating abnormal cellular proliferation and/or a viral infection, particularly by HIV, HCV or HBV. Consequently, the compounds of the present invention interfere with the replication cycle of a virus and are also useful as antiviral agents, or interfere with host cellular biochemical process and are also useful as antiproliferative agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from viral infection and/or cell proliferation. The invention also relates to methods of treating a viral infection and/or cell proliferation in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention relates to novel antiviral/anti-proliferative compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral infection in a subject in need of such therapy with said compounds. </p>
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Inhibitors of human immunodeficiency virus replication (Fri, 10 Jun 2016)
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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Compounds useful as inhibitors of ATR kinase (Fri, 10 Jun 2016)
The present invention relates to pyrazine compounds, pharmaceutical compositions comprising them, and methods for inhibiting ATR protein kinase for treating various diseases, disorders, and conditions including cancer, HIV, hepatitis, adenovirus and psoriasis. Additionally the invention discloses processes for preparing the compounds, intermediates used in the preparation, and methods of using the compounds in in vitro applications including the study of kinases in biological and pathological phenomena, the study of intracellular signal transduction pathways mediated by such kinases, and the comparative evaluation of new kinase inhibitors.
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COMPOSITIONS HAVING C-17 AND C-3 MODIFIED TRITERPENOIDS WITH HIV MATURATION INHIBITORY ACTIVITY (Fri, 03 Jun 2016)
<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, C-17 and C-3 modified triterpenoids 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="136.48mm" wi="72.56mm" file="US20160151387A1-20160602-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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COMPOUNDS USEFUL FOR TREATING DISEASES CAUSED BY RETROVIRUSES (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">Methods for preventing or treating retroviral infection not HIV and/or for preventing, inhibiting or treating a disease caused by the retroviral infection include contacting a cell with compound (I)</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="21.59mm" wi="65.28mm" file="US20160151348A1-20160602-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> </ul> </li> </ul> </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="12.28mm" wi="9.99mm" file="US20160151348A1-20160602-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">means a pyridazine, pyrimidine or pyrazine group, R independently represent a hydrogen atom, halogen atom or group chosen among a —CN, hydroxyl, —COOR<sub>1</sub>, (C<sub>1</sub>-C<sub>3</sub>)fluoroalkyl, (C<sub>1</sub>-C<sub>3</sub>)fluoroalkoxy, —NO<sub>2</sub>, —NR<sub>1</sub>R<sub>2</sub>, (C<sub>1</sub>-C<sub>4</sub>)alkoxy, phenoxy and (C<sub>1</sub>-C<sub>3</sub>)alkyl group, the alkyl being optionally mono-substituted by hydroxyl group, n is 1, 2 or 3, n′ is 1 or 2, R′ is a hydrogen atom, halogen atom or group chosen among (C<sub>1</sub>-C<sub>3</sub>)alkyl group, hydroxyl group, —COOR<sub>1 </sub>group, —NO<sub>2 </sub>group, —NR<sub>1</sub>R<sub>2 </sub>group, morpholinyl or morpholino group, N-methylpiperazinyl group, (C<sub>1</sub>-C<sub>3</sub>)fluoroalkyl group, (C<sub>1</sub>-C<sub>4</sub>)alkoxy group and —CN group, Z is N or C, Y is N or C, X is N or C, W is N or C, T is N or C, U is N or C.</p>
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Inhibitors of viral replication, their process of preparation and their therapeutical uses (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.</p>
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THERAPEUTIC COMPOUNDS (Fri, 03 Jun 2016)
<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="28.62mm" wi="67.56mm" file="US20160152582A1-20160602-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">or salts thereof are provided. 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 are also provided.</p>
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PRODRUGS OF SUBSTITUTED AZAINDOLEOXOACETIC PIPERAZINE DERIVATIVES (Fri, 03 Jun 2016)
<p id="p-0001" num="0000">This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.</p>
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Novel Therapeutic and Diagnostic Means (Fri, 27 May 2016)
<p id="p-0001" num="0000">Disclosed is a method for treatment of HIV related diseases comprising targeting complexes between on the one hand the C5 domain of gp120 and on the other hand gp41 or the C2 domain of gp120. The complexes may be stabilised by administering compounds, such as antibodies, capable of directly interacting with and stabilising the complex, or by immunizing with C5 and gp41/C2 derived material so as to induce antibodies that bind to and stabilise the complex.</p>
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DOLUTEGRAVIR SALTS (Fri, 27 May 2016)
<p id="p-0001" num="0000">Dolutegravir potassium salt and solid state forms thereof are provided, as well as methods of making and interconverting these forms. The Dolutegravir potassium forms, and pharmaceutical compositions containing them, may be used to treat subjects in need of medical treatment, such as for HIV infection.</p>
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Non-nucleoside reverse transcriptase inhibitors (Fri, 27 May 2016)
<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="35.48mm" wi="55.12mm" file="US09718819-20170801-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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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OXOLUPENE DERIVATIVES (Fri, 20 May 2016)
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, 20 May 2016)
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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EXTENDED BETULINIC ACID ANALOGS (Fri, 20 May 2016)
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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Extended betulinic acid analogs (Fri, 20 May 2016)
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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INHIBITORS OF HIV REPLICATION (Fri, 13 May 2016)
The present invention relates to novel 2,3,4-substituted 5,6,7,8 tetrahydro[1]benzothieno[2,3-b]pyridine compounds and pharmaceutically acceptable salts thereof, to compositions containing such compounds and to the use of such compounds as inhibitors of HIV replication.
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HUMAN IMMUNODEFICIENCY VIRUS (HIV)-NEUTRALIZING ANTIBODIES (Fri, 13 May 2016)
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-HIV1 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 glp20 are provided. Immunogens for generating anti-HVIl bNabs are also provided. Furthermore, method for vaccination using suitable epitopes are provided.
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BORONIC ACID INHIBITORS OF HIV PROTEASE (Sat, 07 May 2016)
Protease inhibitors, particularly aspartyl protease inhibitors, and more particularly HIV protease inhibitors which are boronated to enhance activity or to enhance entry into cells. Compounds, prodrugs and salts thereof of this invention contain phenylboronate groups, in particular p-B(OH)2-phenyl groups, benzoxaborole groups or borono-pyridyl groups or analogous groups in which the boronate group is protected. Methods for treating AIDS and ARC as well as providing a method for treating or preventing HIV infection.
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ALKALOIDS FROM SPONGE, SCAFFOLDS FOR THE INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS (HIV) (Sat, 07 May 2016)
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.
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3-ALKYL PYRIDINIUM COMPOUND FROM RED SEA SPONGE WITH POTENT ANTIVIRAL ACTIVITY (Sat, 07 May 2016)
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 R1 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.
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PROCESS FOR THE PREPARATION OF AMINO ALCOHOL DERIVATIVES OR SALTS THEREOF (Sat, 07 May 2016)
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 5 Abacavir. The present invention more specifically relates to a process for the preparation of (1S, 4R)-4-amino-2-cyclopentene-1-methanol of Formula IIIa. 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.
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SALTS OF VALPROIC ACID WITH PIPERAZINE, ETHYLENEDIAMINE, LYSINE AND/OR EICOSAPENTAENOIC ECID (EPA) AMINE DERIVATIVES FOR THE TREATMENT OF EPILEPSY (Sat, 07 May 2016)
The compositions and compounds of formula I, formula II, formula III and formula IV which includes a salt of valproic acid or its polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II, formula III and formula IV and methods for treating or preventing neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, migraine, schizophrenia, depression, Alzheimer's disease, cancer, HIV and familial adenomatous polyposis.
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DERIVATIVES OF BETULIN (Fri, 06 May 2016)
<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="47.58mm" wi="74.25mm" file="US20160120878A1-20160505-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 thereof. Compounds of the present invention are useful for the treatment or prevention of HIV.</li> </ul> </li> </ul> </p>
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PEPTIDES WITH ANTAGONISTIC ACTIVITIES AGAINST NATURAL CXCR4 (Fri, 06 May 2016)
<p id="p-0001" num="0000">A peptide effective in blocking the CXC-chemokine receptor 4 (CXCR4) mediated HIV-1 NL4-3 (X4-tropic) infection with an IC<sub>50 </sub>value of less than 50 μM.</p>
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COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS (Fri, 06 May 2016)
<p id="p-0001" num="0000">The invention relates to the compounds of formula I or its pharmaceutical acceptable salts, as well as polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, and methods for treating or preventing neurological disorders may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection. Such compositions may be used to treatment of epilepsy, bipolar disorder, migraine, schizophrenia, depression, Alzheimer's disease, cancer, HIV and familial adenomatous polyposis.</p>
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Immunogenic compositions and a process for producing same (Fri, 06 May 2016)
<p id="p-0001" num="0000">The present invention provides a modified HIV envelope glycoprotein (Env) antigen or a lipid containing vehicle comprising same. The Env antigen comprises one of a second site suppressor mutation in residue 674 of the membrane proximal ectodomain region (MPER) of HIV gp41; a second site suppressor mutation which ablates a glycosylation site in the variable region (V1) region of gp120; or a second site suppressor mutation ablating a glycosylation site in the V1 region of gp120 and a second site suppressor mutation in residue 674 of the MPER of HIV gp41. It is preferred that the lipid containing vehicle is a HIVLP.</p>
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Boronic acid inhibitors of HIV protease (Fri, 06 May 2016)
<p id="p-0001" num="0000">Protease inhibitors, particularly aspartyl protease inhibitors, and more particularly HIV protease inhibitors which are boronated to enhance activity or to enhance entry into cells. Compounds, prodrugs and salts thereof of this invention contain phenylboronate groups, in particular p -B(OH)<sub>2</sub>-phenyl groups, benzoxaborole groups or borono-pyridyl groups or analogous groups in which the boronate group is protected. Methods for treating AIDS and ARC as well as providing a method for treating or preventing HIV infection.</p>
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PLATINUM-CATALYZED SILICONE DRUG DELIVERY DEVICES AND METHODS OF USE THEREOF (Fri, 29 Apr 2016)
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.
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THERAPEUTIC COMPOUNDS (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">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 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="27.52mm" wi="55.80mm" file="US20160108030A1-20160421-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Bilaterally-substituted tricyclic compounds for the treatment of human immunodeficiency virus type-1 (HIV-1) infection and other diseases (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The invention relates to novel bilaterally-substituted tricyclic compounds and pharmaceutical compositions containing them, for use as medicaments. Due to their ability to interact with an internal RNA loop and to mimic a protein α-helix these compounds are effective in the treatment and/or prevention of HIV-1 (Human Immunodeficiency Virus-1) infection and other diseases such as those caused by other RNA viruses and by gram-positive and gram-negative bacteria, or infectious or chronic diseases responsive to inhibition of DNA transcription, or infectious or chronic diseases where these compounds can be used to modulate the function of RNA internal loops, or infectious or chronic diseases where these compounds can be used as agonists or inhibitors of α-helical proteins in interaction with other biomolecules.</p>
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Fused tricyclic heterocyclic compounds as HIV integrase inhibitors (Fri, 22 Apr 2016)
<p id="p-0001" num="0000">The present invention relates to Fused Tricyclic Heterocycle Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein R<sup>1</sup>-R<sup>8</sup>, A, X and n 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="33.44mm" wi="58.00mm" file="US09643982-20170509-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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TRIAMINOTRIAZINE PICOLINONITRILE DERIVATIVES AS POTENT REVERSE TRANSCRIPTASE INHIBITOR OF HIV-1 (Fri, 22 Apr 2016)
The present invention discloses triamino triazine picolinonitriles of formula- I useful for treating or reducing the severity of hyperproliferative diseases by inhibiting metastasis, or in the treatment or prevention of human immunodeficiency virus (HIV) infections. The invention further discloses process for preparation of compounds of formula-I and pharmaceutical composition thereof.
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COMPOSITIONS AND METHODS FOR REACTIVATING LATENT IMMUNODEFICIENCY VIRUS (Fri, 22 Apr 2016)
The present disclosure provides compositions and methods for reactivating latent immunodeficiency virus. The present disclosure provides compositions and methods for treating an immunodeficiency virus infection. The present disclosure provides a method of reactivating latent human immunodeficiency virus (HIV) integrated into the genome of a cell infected with HIV, the method comprising contacting the cell with a Smyd2 inhibitor that reactivates latent HIV integrated into the genome of the cell.
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INDUCTION OF GATA2 BY HDAC1 AND HDAC2 INHIBITORS (Fri, 15 Apr 2016)
Provided herein are compounds, pharmaceutical compositions comprising such compounds, and methods of using such compounds to treat diseases or disorders associated with Gata2 deficiency, particularly diseases or disorders that involve any type of HDAC1 and/or HDAC2 expression. Such diseases include acute myeloid leukemia (AML); familial myelodysplastic syndrome (MDS); leukemia; sickle-cell anemia; beta-thalassemia; monocytopenia and mycobacterial infections; dendritic cell, nonocyte, B, and natural killer lymphoid deficiency; Emberger syndrome; asymptomatic neurocognitive impairment; mild neurocognitive disorder; and HIV- associated dementia.
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BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS (Fri, 25 Mar 2016)
<p id="p-0001" num="0000">The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-H's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-H's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.</p>
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THERAPEUTIC COMPOUNDS (Fri, 25 Mar 2016)
<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="42.25mm" wi="58.50mm" file="US20160083368A1-20160324-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">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 Retroviridae viral infection including an infection caused by the HIV virus.</p>
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Compounds for inhibiting drug-resistant strains of HIV-1 integrase (Fri, 25 Mar 2016)
<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="24.81mm" wi="61.30mm" file="US09676771-20170613-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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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Substituted Quinolizine Derivatives useful as HIV integrase inhibitors (Fri, 25 Mar 2016)
The present invention relates to Substituted Quinolizine Derivatives of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, R<sp>1</sp>, R<sp>2</sp>, R<sp>3</sp>, R<sp>4</sp>, R<sp>5</sp>, R<sp>9</sp> and R<sp>10</sp> 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.
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SUBSTITUTED AZAINDOLEOXOACETIC PIPERAZINE DERIVATIVES (Fri, 18 Mar 2016)
<p id="p-0001" num="0000">This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives having the Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="15.24mm" wi="69.93mm" file="US20160075703A1-20160317-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein Q is</p> <p id="p-0004" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="26.59mm" wi="32.77mm" file="US20160075703A1-20160317-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005" num="0000">These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.</p>
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INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 18 Mar 2016)
Compounds of Formula (I), including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth:
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Selective HDAC1 and HDAC2 inhibitors (Fri, 11 Mar 2016)
<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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Therapeutic compounds (Fri, 11 Mar 2016)
<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="25.15mm" wi="49.61mm" file="US09789089-20171017-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> 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 Retroviridae viral infection including an infection caused by the HIV virus. </p>
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RECOMBINANT HIV-1 ENVELOPE PROTEINS AND THEIR USE (Fri, 11 Mar 2016)
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.
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Substituted pyrido[1,2-a]pyrazines as HIV integrase inhibitors (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">The present invention relates to 4-Pyridone Compounds of Formula (I); and pharmaceutically acceptable salts and prodrugs thereof, wherein A, 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 4-Pyridone Compound, and methods of using the 4-Pyridone Compounds for treating or preventing HIV infection in a subject or the clinical manifestations thereof.</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="US09493479-20161115-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Synthesis of carbamoylpyridone HIV integrase inhibitors and intermediates (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">The invention is a process for the preparation of a compound of the following formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="27.77mm" wi="55.46mm" file="US09365587-20160614-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R is —CHO, —CH(OH)<sub>2 </sub>or —CH(OH)(OR<sup>4</sup>); P<sup>1 </sup>is H or a hydroxyl protecting group; P<sup>3 </sup>is H or a carboxy protecting group; R<sup>3 </sup>is H, halogen, hydroxy, optionally substituted lower alkyl, optionally substituted cycloalkyl, etc.; R<sup>x </sup>is H, halogen or R<sup>2</sup>—X—NR<sup>1</sup>—C(O)—; etc. as defined in the specification. The compounds are useful as intermediates in synthesizing compounds having HIV integrase inhibitory activity. </p>
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Nucleoside and nucleotide derivatives (Fri, 04 Mar 2016)
<p id="p-0001" num="0000">The present invention discloses compounds of formula (I), 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="25.32mm" wi="55.29mm" file="US09675632-20170613-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> which inhibit, preventing or treating abnormal cellular proliferation and/or a viral infection, particularly by HIV, HCV or HBV. Consequently, the compounds of the present invention interfere with the replication cycle of a virus and are also useful as antiviral agents, or interfere with host cellular biochemical process and are also useful as antiproliferative agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from viral infection and/or cell proliferation. The invention also relates to methods of treating a viral infection and/or cell proliferation in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention relates to novel antiviral/anti-proliferative compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral infection in a subject in need of such therapy with said compounds. </p>
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NUCLEOSIDE AND NUCLEOTIDE DERIVATIVES (Fri, 04 Mar 2016)
The present invention discloses compounds of formula (I), or a pharmaceutically acceptable salt thereof: (I) which inhibit, preventing or treating abnormal cellular proliferation and/or a viral infection, particularly by HIV, HCV or HBV. Consequently, the compounds of the present invention interfere with the replication cycle of a virus and are also useful as antiviral agents, or interfere with host cellular biochemical process and are also useful as antiproliferative agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from viral infection and/or cell proliferation. The invention also relates to methods of treating a viral infection and/or cell proliferation in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention relates to novel antiviral/anti-proliferative compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral infection in a subject in need of such therapy with said compounds.
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ANTIRETROVIRAL AGENTS (Fri, 04 Mar 2016)
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 Retroviridae viral infection including an infection caused by the HIV virus.
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IMIDAZO[1,2-A]PYRIDINE DERIVATIVES FOR USE AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Fri, 04 Mar 2016)
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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Polycyclic-carbamoylpyridone compounds and their use for the treatment of HIV infections (Fri, 04 Mar 2016)
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 R1, X, Y1, Y2, 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 (Fri, 04 Mar 2016)
Compounds for use in the treatment of human immunodeficiency virus (HIV) infection are disclosed. The compounds have the following Formula (I): (I) including stereoisomers and pharmaceutically acceptable salts thereof, wherein L, R<sp>1</sp>, R<sp>5</sp>, W, X, Y<sp>1</sp>, Y<sp>2</sp>, 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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2-keto amide derivatives as HIV attachment inhibitors (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">Compounds of Formula I, including pharmaceutically acceptable salts thereof: I useful as HIV attachment inhibitors.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="18.80mm" wi="69.85mm" file="US09586957-20170307-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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PIPERAZINE AND HOMOPIPERAZINE DERIVATIVES AS HIV ATTACHMENT INHIBITORS (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">Compounds of Formula I, including pharmaceutically acceptable salts thereof, are useful as HIV attachment inhibitors.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="18.80mm" wi="46.57mm" file="US20160052923A1-20160225-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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ANTIVIRAL JAK INHIBITORS USEFUL IN TREATING OR PREVENTING RETROVIRAL AND OTHER VIRAL INFECTIONS (Fri, 26 Feb 2016)
<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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3-amidobenzamides and uses thereof for increasing cellular levels of A3G and other A3 family members (Fri, 26 Feb 2016)
<p id="p-0001" num="0000">Disclosed are novel benzamide compounds and the uses thereof for treating diseases and disorders in a patient in need thereof by increasing cellular levels of A3G and/or other members of the A3 family of proteins in the patient. The disclosed compounds include 3-benzamide compounds that may be administered treat an HIV-1 infection or cancer in a patient.</p>
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3-AMIDOBENZAMIDES AND USES THEREOF FOR INCREASING CELLULAR LEVELS OF A3G (Fri, 26 Feb 2016)
Disclosed are novel benzamide compounds and the uses thereof for treating diseases and disorders in a patient in need thereof by increasing cellular levels of A3G and/or other members of the A3 family of proteins in the patient. The disclosed compounds include 3-benzamide compounds that may be administered to treat an HIV- 1 infection or cancer in a patient.
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SUBSTITUTED SPIROPYRIDO[1,2-a]PYRAZINE DERIVATIVE AND PHARMACEUTICAL USE OF SAME AS HIV INTEGRASE INHIBITOR (Fri, 19 Feb 2016)
<p id="p-0001" num="0000">[Problem] Provided is a substituted spiropyrido[1,2-a]pyrazine derivative or a pharmaceutically acceptable salt thereof, which is useful as an anti-HIV agent.</p> <p id="p-0002" num="0000">[Solving Means] 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-0003" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="88.98mm" wi="75.10mm" file="US20160046641A1-20160218-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004" num="0000">wherein each symbol is as defined in the specification.</p>
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INHIBITORS OF HIV-1 ENTRY AND METHODS OF USE THEREOF (Fri, 19 Feb 2016)
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.
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Compositions and methods for treating viral infections (Fri, 12 Feb 2016)
<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="US09539276-20170110-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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Inhibitors of human immunodeficiency virus replication (Fri, 12 Feb 2016)
<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="31.33mm" wi="61.38mm" file="US09540393-20170110-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Inhibitors of viral replication, their process of preparation and their therapeutical uses (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.</p>
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Tannin inhibitors of HIV (Fri, 12 Feb 2016)
<p id="p-0001" num="0000">The invention provides a method to prevent or treat HIV-infection with synthetic tannins, and pharmaceutical compositions comprising synthetic tannins.</p>
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NOVEL ANTIBODIES FOR THE TREATMENT OF HIV (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">The present invention relates to novel isolated antibodies, or the derivatives or antigen binding fragments of same, capable of binding to CXCR4 but also of inducing conformational changed of the CXCR4 homodimers and able to inhibit HIV-1 primary isolate replication in PBMC.</p> <p id="p-0002" num="0000">More particularly, the present invention relates to the 515H7 and 301aE5 monoclonal antibodies, specific to the CXCR4 protein, as well as their use for the treatment of HIV infection. Pharmaceutical compositions comprising such antibodies and a process for the selection of such antibodies are also covered.</p>
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Immunovir and Components, Immunovir A, B, C, D Utility and Useful Processes (Fri, 05 Feb 2016)
<p id="p-0001" num="0000">A complete remedy for AIDS is difficult to obtain. As such, a useful process was designed to search for an anti-HIV<sub>1 </sub>agent that has an immuno response modification activity capable of releasing immuno suppression, activating killer cells to destroy persistent infection cells, elevating antibody titer to activate ADCC activity, and vice versa.</p> <p id="p-0002" num="0000">The process consists of 4 elements: guinea pig or mouse peritoneal derived adherent macrophages/monocytes as effector cells; cyclophosphamide as an immuno suppressor; chicken RBC as target cells; and the anti-HIV<sub>1 </sub>agent candidate to be examined.</p> <p id="p-0003" num="0000">Immunovir and components were isolated from Pyrus serotina Rehder and other species of Rosaceae by column chromatography.</p> <p id="p-0004" num="0000">Another useful process is the comparison of fluorescent antibody titer patterns among one round, two round, and non-medicated infected monkeys.</p> <p id="p-0005" num="0000">The results of such processes can show that the anti-HIV<sub>1 </sub>agent, such as these immunovirs, are noble candidates for the complete remedy of AIDS.</p>
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NOVEL HYDRATES OF DOLUTEGRAVIR SODIUM (Fri, 05 Feb 2016)
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.
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Novel hydrates of dolutegravir sodium (Thu, 04 Feb 2016)
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 and to the use of said pharmaceutical compositions in the treatment of retroviral infections such as HIV-1 infections.
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PHOSPONATE NUCLEOSIDES USEFUL AS ACTIVE INGREDIENTS IN PHARMACEUTICAL COMPOSITIONS FOR THE TREATMENT OF VIRAL INFECTIONS, AND INTERMEDIATES FOR THEIR PRODUCTION (Thu, 04 Feb 2016)
The present invention relates to novel phosponate nucleosides, more specifically to novel phosponalkoxy substituted nucleosides. The invention further relates to compounds having HIV (Human Immunodeficiency Virus) replication inhibiting properties and to compounds having antiviral activities with respect to other viruses. The invention also relates to methods for preparation of all such compounds and pharmaceutical compositions comprising them. The invention further relates to the use of said compounds as a medicine and in the manufacture of a medicament useful for the treatment of subjects suffering from HIV infection, as well as for treatment of other viral, retroviral or lentiviral infections and to the treatment of animals suffering from FIV, viral, retroviral or lentiviral infections.
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PROCESS FOR PREPARING ATAZANAVIR BISULFATE AND NOVEL FORMS (Thu, 04 Feb 2016)
A process is provided for preparing the HIV protease inhibitor atazanavir bisulfate wherein a solution of atazanavir free base is reacted with concentrated sulfuric acid in an amount to react with less than about 15% by weight of the free base, seeds of Form A crystals of atazanavir bisulfate are added to the reaction mixture, and as crystals of the bisulfate form, additional concentrated sulfuric acid is added in multiple stages at increasing rates according to a cubic equation, to effect formation of Form A crystals of atazanavir bisulfate. A process is also provided for preparing atazanavir bisulfate as Pattern C material.
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Inhibitors of human immunodeficiency virus replication (Fri, 29 Jan 2016)
<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="66.55mm" wi="62.57mm" file="US09527842-20161227-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Therapeutic compounds (Fri, 29 Jan 2016)
<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="US09464096-20161011-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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PHENYL AND TERTBUTYLACETIC ACID SUBSTITUTED PYRIDINONES HAVING ANTI-HIV EFFECTS (Fri, 29 Jan 2016)
Compounds of Formula I are disclosed and methods of treating viral invections with compositions comprising such compounds. Formula I
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THERAPEUTIC COMPOUNDS (Fri, 22 Jan 2016)
<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="70.02mm" file="US20160015690A1-20160121-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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Inhibitors of human immunodeficiency virus replication (Fri, 22 Jan 2016)
<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="25.91mm" wi="60.71mm" file="US09580431-20170228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Bicyclic compounds useful for treating diseases caused by retroviruses (Fri, 22 Jan 2016)
Described herein are methods for preventing or treating a retroviral infection and/or for preventing, inhibiting or treating a disease caused by the retroviral infection. In certain aspects, the methods described herein include contacting a cell in need thereof with compound (I), wherein (II) means a pyridazine, a pyrimidine or a pyrazine group, R independently represent a hydrogen atom, a halogen atom or a group chosen among a –CN group, a hydroxyl group, a –COOR<sb>1 </sb>group, a (C<sb>1</sb> -C<sb>3</sb>)fluoroalkyl group, a (C<sb>1</sb> -C<sb>3</sb>)fluoroalkoxy group, a –NO<sb>2</sb> group, a –NR<sb>1</sb>R<sb>2</sb> group, a (C<sb>1</sb>-C<sb>4</sb>)alkoxy group, a phenoxy group and a (C<sb>1</sb>-C<sb>3</sb>)alkyl group, said alkyl being optionally mono-substituted by a hydroxyl group, n is 1, 2 or 3, n' is 1 or 2, R' is a hydrogen atom, a halogen atom or a group chosen among a (C<sb>1</sb>-C<sb>3</sb>)alkyl group,, a hydroxyl group, a –COOR<sb>1</sb> group, a –NO<sb>2</sb> group, a –NR<sb>1</sb>R<sb>2</sb> group, a morpholinyl or a morpholino group, a N-methylpiperazinyl group, a (C<sb>1</sb>-C<sb>3</sb>)fluoroalkyl group, a (C<sb>1</sb>-C<sb>4</sb>)alkoxy group and a –CN group, Z is N or C, Y is N or C, X is N or C, W is N or C, T is N or C, U is N or C, to prevent or treat the retroviral infection and/or for preventing, inhibiting or treating a disease caused by the retroviral infection, wherein the retroviral infection is not HIV and the disease caused by the retroviral infection is not AIDS.
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Inhibitors of viral replication, their process of preparation and their therapeutical uses (Fri, 22 Jan 2016)
The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.
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INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION (Thu, 21 Jan 2016)
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 (Thu, 21 Jan 2016)
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. Formule (I)
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