PERIPHERAL OPIOID RECEPTOR ANTAGONISTS AND USES THEREOF (Fri, 21 Mar 2014)
<p id="p-0001" num="0000">The present invention provides a compound of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.61mm" wi="53.59mm" file="US20140080854A1-20140320-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein X<sup>−</sup>, R<sup>1</sup>, and R<sup>2 </sup>are as defined herein, and compositions thereof.</p>
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PROCESSES FOR THE CONVERGENT SYNTHESIS OF CALICHEAMICIN DERIVATIVES (Fri, 21 Mar 2014)
<p id="p-0001" num="0000">This invention describes processes for the convergent synthesis of calicheamicin derivatives, and similar analogs using bifunctional and trifunctional linker intermediates.</p>
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Rapamycin hydroxyesters (Wed, 19 Feb 2014)
<p id="p-0001" num="0000">A compound of the structure</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="60.71mm" wi="64.77mm" file="USRE044768-20140218-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000">wherein R<sup>1 </sup>and R<sup>2 </sup>are each, independently, hydrogen or —CO(CR<sup>3</sup>R<sup>4</sup>)<sub>b</sub>(CR<sup>5</sup>R<sup>6</sup>)<sub>d</sub>CR<sup>7</sup>R<sup>8</sup>R<sup>9</sup>;</li> <li id="ul0001-0002" num="0000">R<sup>3 </sup>and R<sup>4 </sup>are each, independently, hydrogen, alkyl, alkenyl, alkynyl, trifluoromethyl, or —F;</li> <li id="ul0001-0003" num="0000">R<sup>5 </sup>and R<sup>6 </sup>are each, independently, hydrogen, alkyl, alkenyl, alkynyl, —(CR<sup>3</sup>R<sup>4</sup>)<sub>f</sub>OR<sup>10</sup>, —CF<sub>3</sub>, —F, or —CO<sub>2</sub>R<sup>11</sup>, or R<sup>5 </sup>and R<sup>6 </sup>may be taken together to form X or a cycloalkyl ring that is optionally mono-, di-, or tri-substituted with —(CR<sup>3</sup>R<sup>4</sup>)<sub>f</sub>OR<sup>10</sup>;</li> <li id="ul0001-0004" num="0000">R<sup>7 </sup>is hydrogen, alkyl, alkenyl, alkynyl, —(CR<sup>3</sup>R<sup>4-</sup>)<sub>f</sub>OR<sup>10</sup>, —CF<sub>3</sub>, —F, or CO<sub>2</sub>R<sup>11</sup>;</li> <li id="ul0001-0005" num="0000">R<sup>8 </sup>and R<sup>9 </sup>are each, independently, hydrogen, alkyl, alkenyl, alkynyl, —(CR<sup>3</sup>R<sup>4</sup>)<sub>f</sub>OR<sup>10</sup>, —CF<sub>3</sub>, —F, or —CO<sub>2</sub>R<sup>11</sup>, or R<sup>8 </sup>and R<sup>9 </sup>may be taken together to form X or a cycloalkyl ring that is optionally mono-, di-, or tri-substituted with —(CR<sup>3</sup>R<sup>4-</sup>)<sub>f</sub>OR<sup>10</sup>;</li> <li id="ul0001-0006" num="0000">R<sup>10 </sup>is hydrogen, alkyl, alkenyl, alkynyl, tri-(alkyl)silyl, tri-(alkyl)silylethyl, triphenylmethyl, benzyl, alkoxymethyl, tri-(alkyl)silylethoxymethyl, chloroethyl, or tetrahydropyranyl;</li> <li id="ul0001-0007" num="0000">R<sup>11 </sup>is hydrogen, alkyl, alkenyl, alkynyl, or phenylalkyl;</li> <li id="ul0001-0008" num="0000">X is 5-(2,2-dialkyl)[1,3]dioxanyl, 5-(2,2-dicycloalkyl)[1,3]dioxanyl, 4-(2,2-dialkyl)[1,3]dioxanyl, 4-(2,2-dicycloalkyl)[1,3]dioxanyl, 4-(2,2dialkyl)[1,3]dioxalanyl, or 4-(2,2-dicycloalkyl)[1,3]dioxalanyl;</li> <li id="ul0001-0009" num="0000">b=0-6;</li> <li id="ul0001-0010" num="0000">d=0-6; and</li> <li id="ul0001-0011" num="0000">f=0-6 <br/> with the proviso that R<sup>1 </sup>and R<sup>2 </sup>are both not hydrogen and further provided that either R<sup>1 </sup>or R<sup>2 </sup>contains at least one —(CR<sup>3</sup>R<sup>4</sup>)<sub>f</sub>OR<sup>10</sup>, X, or —(CR<sup>3</sup>R<sup>4</sup>)<sub>f</sub>OR<sup>10 </sup>substituted cycloalkyl group, or a pharmaceutically acceptable salt thereof which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent. </li> </ul> </p>
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IMMUNOGENIC COMPOSITIONS OF STAPHYLOCOCCUS AUREUS ANTIGENS (Fri, 17 Jan 2014)
<p id="p-0001" num="0000">The present invention relates to immunogenic compositions, comprising polypeptides and polysaccharides from <i>Staphylococcus aureus</i>. The present invention also relates to immunogenic compositions, comprising <i>Staphylococcus aureus </i>capsule polysaccharides conjugated to a carrier protein. In addition, the invention relates to methods of inducing an immune response in subjects against <i>Staphylococcus aureus </i>using immunogenic compositions of the <i>Staphylococcus aureus </i>polypeptides and capsule polysaccharides.</p>
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LOCAL VASCULAR DELIVERY OF TRICHOSTATIN A ALONE OR IN COMBINATION WITH SIROLIMUS TO PREVENT RESTENOSIS FOLLOWING VASCULAR INJURY (Fri, 03 Jan 2014)
<p id="p-0001" num="0000">Medical devices, and in particular implantable medical devices, may be coated with any number of biocompatible materials. Therapeutic drugs, agents or compounds may be mixed with the biocompatible materials and affixed to at least a portion of the medical device. These therapeutic drugs, agents or compounds may also further reduce a biological organism's reaction to the introduction of the medical device to the organism. In addition, these therapeutic drugs, agents and/or compounds may be utilized to promote healing, including the formation of blood clots. Also, the devices may be modified to promote endothelialization. Various materials and coating methodologies may be utilized to maintain the drugs, agents or compounds on the medical device until delivered and positioned. In addition, various polymer combinations may be utilized to control the elution rates of the therapeutic drugs, agents and/or compounds from the implantable medical devices.</p>
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CRYSTAL FORMS OF (R)-N-METHYLNALTREXONE BROMIDE AND USES THEREOF (Fri, 03 Jan 2014)
<p id="p-0001" num="0000">The present invention provides a new forms of (R)—N-methylnaltrexone, and compositions thereof, useful as a peripheral mu opioid receptor antagonist.</p>
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ORAL FORMULATIONS AND LIPOPHILIC SALTS OF METHYLNALTREXONE (Fri, 13 Dec 2013)
<p id="p-0001" num="0000">The present invention provides compositions comprising methylnaltrexone or a salt thereof, and compositions and formulations thereof, for oral administration.</p>
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Triazine compounds as P13 kinase and MTOR inhibitors (Fri, 29 Nov 2013)
<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="22.10mm" wi="49.61mm" file="US08748421-20140610-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is</li> </ul> </li> </ul> </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="24.05mm" wi="53.26mm" file="US08748421-20140610-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and R<sup>2</sup>, R<sup>4</sup>, and R<sup>6-9 </sup>are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed. </p>
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MALEATE SALTS OF (E)-N--4-(DIMETHYLAMINO)-2-BUTENAMIDE AND CRYSTALLINE FORMS THEREOF (Fri, 25 Oct 2013)
<p id="p-0001" num="0000">The present invention relates to maleate salt forms of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide, methods of preparing crystalline maleate salt forms, the associated compounds, and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family.</p>
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Peripheral opioid receptor antagonists and uses thereof (Fri, 25 Oct 2013)
<p id="p-0001" num="0000">The present invention provides a compound of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.02mm" wi="53.51mm" file="US08772310-20140708-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein X<sup>−</sup>, R<sup>1</sup>, and R<sup>2 </sup>are as defined herein, and compositions thereof; useful as a peripheral mu opioid receptor antagonist. </p>
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Cyclothiocarbamate derivatives as progesterone receptor modulators (Fri, 04 Oct 2013)
<p id="p-0001" num="0000">Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.13mm" wi="32.51mm" file="US08796266-20140805-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, and Q<sup>1 </sup>are defined herein. </p>
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Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof (Thu, 15 Aug 2013)
The present invention relates to maleate salt forms of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy]anilino}-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide, methods of preparing crystalline maleate salt forms, the associated compounds, and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family.
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Maleate salts of (e)-n-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof (Thu, 25 Jul 2013)
The present invention relates to maleate salt forms of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy]anilino}-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide, methods of preparing crystalline maleate salt forms, the associated compounds, and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family.
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TANAPROGET DERIVATIVES, METABOLITES, AND USES THEREOF (Fri, 07 Jun 2013)
<p id="p-0001" num="0000">A method of generating synthetic metabolites of tanaproget derivatives thereof is provided. These compounds and methods of using these derivatives for detecting tanaproget metabolites in samples are provided.</p>
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Triazine compounds as PI3 kinase and mTOR inhibitors (Fri, 03 May 2013)
<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="22.18mm" wi="49.61mm" file="US08575159-20131105-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is</li> </ul> </li> </ul> </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="24.05mm" wi="54.02mm" file="US08575159-20131105-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and R<sup>2</sup>, R<sup>4</sup>, and R<sup>6-9 </sup>are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed. </p>
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Cyclothiocarbamate derivatives as progesterone receptor modulators (Fri, 22 Mar 2013)
<p id="p-0001" num="0000">Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.13mm" wi="32.51mm" file="US08466146-20130618-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, and Q<sup>1 </sup>are defined herein. </p>
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Peripheral opioid receptor and antagonists and uses thereof (Thu, 07 Mar 2013)
The present invention provides a compound of formula I wherein X-, R 1 and R 2 are as defined herein, and compositions thereof, useful as a peripheral mu opioid receptor antagonist.
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Processes for the convergent synthesis of calicheamicin derivatives (Fri, 18 Jan 2013)
<p id="p-0001" num="0000">This invention describes processes for the convergent synthesis of calicheamicin derivatives, and similar analogs using bifunctional and trifunctional linker intermediates.</p>
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Peripheral opioid receptor antagonists and uses thereof (Fri, 11 Jan 2013)
<p id="p-0001" num="0000">The present invention provides a compound of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.63mm" wi="53.51mm" file="US08455644-20130604-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein X<sup>−</sup>, R<sup>1</sup>, and R<sup>2 </sup>are as defined herein, and compositions thereof. </p>
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Purification of progesterone receptor modulators (Fri, 11 Jan 2013)
<p id="p-0001" num="0000">Methods for purifying a compound of formula I are provided, wherein A, B, X, Q, and R<sup>1 </sup>are defined herein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.69mm" wi="51.56mm" file="US08609712-20131217-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The methods include mixing the compound of formula I and a solvent; adding a base to the solvent; and precipitating purified compound of formula I.</p>
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Triazine compounds as PI3 kinase and mTOR inhibitors (Fri, 04 Jan 2013)
<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="22.10mm" wi="49.87mm" file="US08445486-20130521-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein: <br/> R<sup>1 </sup>is </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="24.05mm" wi="60.54mm" file="US08445486-20130521-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and R<sup>2</sup>, R<sup>4</sup>, and R<sup>6-9 </sup>are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed. </p>
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Preparation of maleate salt of neratininb and its use (Thu, 27 Dec 2012)
The present invention relates to maleate salt forms of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy]anilino}-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide, methods of preparing crystalline maleate salt forms, the associated compounds, and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family.
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Peripheral opioid receptor antagonists and uses thereof (Fri, 14 Dec 2012)
<p id="p-0001" num="0000">The present invention provides a compound of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.70mm" wi="53.51mm" file="US08420663-20130416-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein X<sup>−</sup>, R<sup>1</sup>, and R<sup>2 </sup>are as defined herein, and compositions thereof. </p>
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Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl)-4-(dimethylamino)-2-buteramide and crystalline forms thereof (Fri, 16 Nov 2012)
<p id="p-0001" num="0000">The present invention relates to maleate salt forms of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide, methods of preparing crystalline maleate salt forms, the associated compounds, and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family.</p>
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STABLE IMMUNOGENIC COMPOSITIONS OF STAPHYLOCOCCUS AUREUS ANTIGENS (Fri, 29 Jun 2012)
The present invention is directed towards a lyophilized or reconstituted multi- antigen or multicomponent immunogenic composition comprising at least one antigen isolated from a staphylococcal bacterium, and methods of making the same.
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Compounds that modulate neuronal growth and their uses (Thu, 12 Apr 2012)
Cyclic peptides and peptidomimetics are provided that bind to and/or modulate activities associated with Trk receptors, including processes associated with the growth and repair of the central nervous system (e.g., neuronal growth and survival, axonal growth, neurite outgrowth and synaptic plasticity). Cyclic peptides and peptidomimetics are also provided that block or reduce the effect of other factors that inhibit growth and/or repair of the central nervous system. Pharmaceutical compositions and other formulations comprising these compounds are provided. In addition, the invention provides methods for using the cyclic peptides and peptidomimetics to modulate Trk mediated activities, including processes such as neuronal growth, survival and recover, axonal growth, neurite outgrowth, and synaptic plasticity. Further, the invention provides methods for promoting central nervous system (CNS) neuron growth by administering a p75 receptor binding agent.
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Shortened purification process for the production of capsular streptococcus pneumoniae polysaccharides (Thu, 05 Apr 2012)
A shortened process for producing a solution containing substantially purified capsular polysaccharides from a cellular Streptococcus pneumoniae lysate broth is described. Ultrafiltering and diafiltering a clarified S. pneumoniae lysate followed by pH adjustment to less than 4.5, preferably about 3.5, precipitated at least 98% of the protein in the solution without seriously affecting polysaccharide yield. Furthermore, following ultrafiltration and diafiltration and acidification to a pH of less than 4.5, filtration using activated carbon precipitated at least 90% of remaining protein without seriously affecting polysaccharide yield. Exemplary, non-limiting S. pneumoniae serotypes that can be purified using the shortened process of the invention are 1, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F. In one embodiment, the Streptococcus pneumoniae cells are lysed using deoxycholate sodium (DOC), while in another embodiment the lytic agent is a non-animal derived lytic agent such as N-lauryl sarcosine sodium (NLS).
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Methods for treating and preventing fibrosis by IL-21 / IL-21R antagonists (Thu, 05 Apr 2012)
The present invention provides methods of screening for compositions useful for treating, ameliorating, or preventing fibrosis and/or fibrosis-associated conditions by measuring changes in the level(s) of IL-21 and/or IL-21 receptor (IL-21R) (e.g., the level of expression of IL-21 and/or IL-21 R protein and/or mRNA, the level of activity of IL-21 and/or IL-21R, the level of interaction of IL-21 with IL-21R). The invention further provides antagonists of IL-21 or IL-21R for the treatment of fibrosis and/or fibrosis-associated conditions. Further provided herein are methods of diagnosing, prognosing, and monitoring the progress (e.g., the course of treatment) of fibrosis and/or fibrosis-associated conditions by measuring the level of IL-21 and/or IL-21R (i.e., the level of activity of IL-21 and/or IL-21R, the level of expression of IL-21 and/or IL-21R (e.g., the level of IL-21 and/or IL-21 R gene products), and/or the level of interaction of IL-21 with IL-21R).
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Oral formulations and lipophilic salts of methylnaltrexone (Fri, 23 Mar 2012)
<p id="p-0001" num="0000">The present invention provides compositions comprising methylnaltrexone or a salt thereof, and compositions and formulations thereof, for oral administration.</p>
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Multivalent Pneumococcal Polysaccharide-Protein Conjugate Composition (Thu, 08 Mar 2012)
An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection.
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Multivalent pneumococcal polysaccharide-protein conjugate composition (Thu, 08 Mar 2012)
An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection.
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Multivalent pneumococcal polysaccharide-protein conjugate composition (Thu, 08 Mar 2012)
An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection.
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Multivalent pneumococcal polysaccharide-protein conjugate composition (Thu, 08 Mar 2012)
An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection.
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Triazine compounds as PI3 kinase and mTOR inhibitors (Fri, 23 Dec 2011)
<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="22.10mm" wi="49.87mm" file="US08217036-20120710-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is</li> </ul> </li> </ul> </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="24.05mm" wi="51.82mm" file="US08217036-20120710-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and R<sup>2</sup>, R<sup>4</sup>, and R<sup>6-9 </sup>are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed. </p>
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Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof (Fri, 23 Dec 2011)
<p id="p-0001" num="0000">The present invention relates to maleate salt forms of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide, methods of preparing crystalline maleate salt forms, the associated compounds, and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family.</p>
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IL-13 BINDING AGENTS (Fri, 28 Oct 2011)
<p id="p-0001" num="0000">Agents (e.g., antibodies and fragments thereof) that bind specifically to IL 13 and modulate the ability of IL-13 to interact with IL-13 receptors and signaling mediators are disclosed.</p>
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Oral formulations and lipophilic salts of methylnaltrexone (Thu, 06 Oct 2011)
The present invention provides compositions comprising methylnaltrexone or a salt thereof, and compositions and formulations thereof, for oral administration.
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ORAL FORMULATIONS AND LIPOPHILIC SALTS OF METHYLNALTREXONE (Fri, 16 Sep 2011)
The present invention provides compositions comprising methylnaltrexone or a salt thereof, and compositions and formulations thereof, for oral administration.
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ORAL FORMULATIONS AND LIPOPHILIC SALTS OF METHYLNALTREXONE (Fri, 16 Sep 2011)
The present invention provides compositions comprising methylnaltrexone or a salt thereof, and compositions and formulations thereof, for oral administration.</p>
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1-ARYL- OR 1-ALKYLSULFONYL-HETEROCYCLYLBENZAZOLES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OF CNS DISORDERS AFFECTED BY 5-HT6 RECEPTORS (Fri, 01 Jul 2011)

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Glycopeptide antibiotics (Fri, 24 Jun 2011)
<p id="p-0001" num="0000">The invention provides compounds of formula</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="63.50mm" wi="61.98mm" file="US08247211-20120821-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> Wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6a</sup>, R<sup>6b</sup>, R<sup>6c</sup>, R<sup>6d</sup>, R<sup>6e </sup>and R<sup>7 </sup>are defined in the specification. These compounds are useful as antibiotic agents. </p>
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MACROLIDES AND METHODS FOR PRODUCING SAME (Fri, 17 Jun 2011)
<p id="p-0001" num="0000">This invention relates, in part, to macrolide compounds, actinomycete strains for producing them, and pharmaceutical compositions containing them.</p>
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Interleukin-17F antibodies and other IL-17F signaling antagonists and uses therefor (Thu, 19 May 2011)
The present invention provides isolated and purified polynucleotides and polypeptides related to the IL-17F signaling pathway. The invention also provides antibodies to IL-17F homodimers and IL-17A/IL-17F heterodimers, and methods of isolating and purifying members of the IL-17 family, including IL-17A/IL-17F heterodimers, from a natural source. The present invention also is directed to novel methods for diagnosing, prognosing, monitoring the progress of, and treating and/or preventing disorders related to IL-17F signaling, i.e., IL-17F-associated disorders, including, but not limited to, inflammatory disorders, such as autoimmune diseases (e.g., arthritis (including rheumatoid arthritis), psoriasis, systemic lupus erythematosus, and multiple sclerosis), respiratory diseases (e.g., COPD, cystic fibrosis, asthma, allergy), transplant rejection (including solid organ transplant rejection) and inflammatory bowel diseases or disorders (IBDs, e.g., ulcerative colitis, Crohn's disease). The present invention is further directed to novel therapeutics and therapeutic targets, and to methods of screening and assessing test compounds for the intervention (treatment) and prevention of disorders related to IL-17F signaling.
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INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS (Fri, 13 May 2011)
Disclosed are compounds of Formula (I): which are useful as antagonists of the CRTH2 receptors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are responsive to inhibition of the binding of endogenous ligands to the CRTH2 receptor are also disclosed. Methods for preparing and using these compounds are further described.
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Succinate salt of O-desmethyl-venlafaxin (Thu, 12 May 2011)
A novel salt of O-desmethyl venlafaxine is provided, O-desmethylvenlafaxine succinate. Pharmaceutical compositions, dosage forms and methods of use are also provided.
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INDOLE BASED RECEPTOR CRTH2 ANTAGONISTS (Fri, 06 May 2011)
<p id="p-0001" num="0000">Disclosed are compounds of Formula (I):</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="41.83mm" wi="59.10mm" file="US20110105509A1-20110505-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">which are useful as antagonists of the CRTH2 receptors. Pharmaceutical compositions containing compounds of Formula (I) and the use of compounds of Formula (I) to treat diseases or disorders that are responsive to inhibition of the binding of endogenous ligands to the CRTH2 receptor are also disclosed. Methods for preparing and using these compounds are further described.</li> </ul> </li> </ul> </p>
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COMPOSITIONS AND METHODS FOR PREPARING STAPHYLOCOCCUS AUREUS SEROTYPE 5 AND 8 CAPSULAR POLYSACCHARIDE CONJUGATE IMMUNOGENIC COMPOSITIONS (Fri, 08 Apr 2011)
The present invention relates to immunogenic conjugates comprising S. aureus serotype 5 and 8 capsular polysaccharides conjugated to carrier proteins and methods for their preparation and use. Methods for making the immunogenic conjugates of the invention involve covalent conjugation of the capsular polysaccharides with the carrier proteins using conjugation chemistry involving either 1,1 carboyl di 1,2,4 triazole (CDT) or 3 (2 pyridyldithio) propionyl hydrazide (PDPH).
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COMPOSITIONS AND METHODS FOR PREPARING STAPHYLOCOCCUS AUREUS SEROTYPE 5 AND 8 CAPSULAR POLYSACCHARIDE CONJUGATE IMMUNOGENIC COMPOSITIONS (Fri, 08 Apr 2011)
The present invention relates to immunogenic conjugates comprising S. aureus serotype 5 and 8 capsular polysaccharides conjugated to carrier proteins and methods for their preparation and use. Methods for making the immunogenic conjugates of the invention involve covalent conjugation of the capsular polysaccharides with the carrier proteins using conjugation chemistry involving either 1,1 carboyl di 1,2,4 triazole (CDT) or 3 (2 pyridyldithio) propionyl hydrazide (PDPH).</p>
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Altered fibronectin-binding protein of staphylococcus aureus (Thu, 31 Mar 2011)
An isolated, altered fibronectin-binding protein (Fnb) of S. aureus having at least one mutation in an amino acid selected from residues corresponding to GIn103, GIn105, Lys157, Lys503, Lys620, Lys702, Lys762, Gln783 and Gln830 of FnbA of S. aureus strain ATCC49525 is described. Replacement of these reactive residues within the fibronectin-binding protein renders this protein less capable than wild-type Fnb of covalently cross-linking with fibronectin and fibrin. The altered fibronectinbinding protein effectively interferes with adhesion of S. aureus to fibronectin and fibrin, and therefore, an immunogenic composition comprising such altered Fnb exhibits improved immunogenic properties and is safer to use.
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1-aryl- or 1-alkylsulfonyl-heterocyclylbenzazoles as 5-hydroxytryptamine-6 ligands (Thu, 24 Mar 2011)
The present invention provides a compound of formula I and the use thereof in the therapeutic treatment of disorders related to or affected by the 5-HT6 receptor. wherein A is C, CR 10 or N; X is N; Y is CR 7 ; R 1 is H, C 1 -C 6 alkylcarbonyl, C 1 -C 6 alkoxycarbonyl or a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl or cycloheteroalkyl group each optionally substituted; R 2 , R 3 , R 4 , R 5 and R 6 are each independently H, halogen, OH or an optionally substituted C 1 -C 6 alkyl group; R 7 is H, halogen or a C 1 -C 6 alkyl, aryl, heteroaryl or C 1 -C 6 alkoxy group each optionally substituted; R 8 is a C 1 -C 6 alkyl, aryl or heteroaryl group each optionally substituted; R 9 is H, halogen or a C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 2 -C 6 alkenyl, aryl or heteroaryl group each optionally substituted; R 10 is H, OH or an optionally substituted C 1 -C 6 alkoxy group; m is an integer of 1, 2 or 3; n is 0 or an integer of 1, 2 or 3; and ----- represents a single bond or a double bond; or a pharmaceutically acceptable salt thereof.
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3-((hetero)aryl)-indazoles as Liver X receptor (LXR) and Th-1 inhibitors for the treatment of cardiovascular diseases (Thu, 17 Mar 2011)
This invention provides compounds of Formula (Ia): wherein: R 1 has various meanings including C 1-6 alkyl, CN, CO 2 R 5 , C(O)R 5 , C 2-6 alkenyl, C 3-8 cycloalkenyl, C 2-6 alkynyl, NR 5 R 6 , C(O)NR 5 R 6 , phenyl, thiophene, C 1-3 alkoxy, halogen and S(O) k R 5 ; R 2 is heteroaryl, substituted with YD; or R 2 is phenyl substituted with up to four substituents YD; R 20 is H or C 1-3 alkyl; and R 4 is H, halogen, methyl or methoxy; and pharmaceutically acceptable salts thereof. The compounds and salts are useful in the treatment or inhibition of Liver X Receptor (LXR) mediated diseases.
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Cyanopyrroles (Fri, 18 Feb 2011)
<p id="p-0001" num="0000">This invention provides a progesterone receptor antagonist of formula 1 having the structure</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="30.65mm" wi="62.31mm" file="US08476262-20130702-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein, T is O, S, or absent; R<sub>1</sub>, and R<sub>2 </sub>are each, independently, hydrogen, alkyl, substituted alkyl; or R<sub>1 </sub>and R<sub>2 </sub>are taken together form a ring and together contain —CH<sub>2</sub>(CH<sub>2</sub>)<sub>n</sub>CH<sub>2</sub>—, —CH<sub>2</sub>CH<sub>2</sub>CMe<sub>2</sub>CH<sub>2</sub>CH<sub>2</sub>—, —O(CH<sub>2</sub>)<sub>p</sub>CH<sub>2</sub>—, —O(CH<sub>2</sub>)<sub>q</sub>O—, —CH<sub>2</sub>CH<sub>2</sub>OCH<sub>2</sub>CH<sub>2</sub>—, or —CH<sub>2</sub>CH<sub>2</sub>NR<sub>7</sub>CH<sub>2</sub>CH<sub>2</sub>—; n=1-5; p=1-4; q=1-4; R<sub>3 </sub>is hydrogen, OH, NH<sub>2</sub>, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, or COR<sup>A</sup>; R<sup>A </sup>is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R<sub>4 </sub>is hydrogen, halogen, CN, NH<sub>2</sub>, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R<sub>5 </sub>is hydrogen, alkyl, or substituted alkyl; R<sub>6 </sub>is hydrogen, alkyl, substituted alkyl, or COR<sup>B</sup>; R<sup>B </sup>is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aminoalkyl, or substituted aminoalkyl; R<sub>7 </sub>is hydrogen or alkyl; or a pharmaceutically acceptable salt thereof. </p>
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Quinolines useful in treating cardiovascular disease (Thu, 17 Feb 2011)
This invention provides compounds of formula (I) that are useful in the treatment or inhibition of LXR mediated diseases.
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INTERLEUKIN-17F ANTIBODIES AND OTHER IL-17F SIGNALING ANTAGONISTS AND USES THEREFOR (Fri, 11 Feb 2011)
<p id="p-0001" num="0000">The present invention provides isolated and purified polynucleotides and polypeptides related to the IL-17F signaling pathway. The invention also provides antibodies to IL-17F homodimers and IL-17A/IL-17F heterodimers, and methods of isolating and purifying members of the IL-17 family, including IL-17A/IL-17F heterodimers, from a natural source. The present invention also is directed to novel methods for diagnosing, prognosing, monitoring the progress of, and treating and/or preventing disorders related to IL-17F signaling, i.e., IL-17F-associated disorders, including, but not limited to, inflammatory disorders, such as autoimmune diseases (e.g., arthritis (including rheumatoid arthritis), psoriasis, systemic lupus erythematosus, and multiple sclerosis), respiratory diseases (e.g., COPD, cystic fibrosis, asthma, allergy), transplant rejection (including solid organ transplant rejection), and inflammatory bowel diseases or disorders (IBDs, e.g., ulcerative colitis, Crohn's disease). The present invention is further directed to novel therapeutics and therapeutic targets, and to methods of screening and assessing test compounds for the intervention (treatment) and prevention of disorders related to IL-17F signaling.</p>
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Heterocyclic Sulfonamide Inhibitors of Beta Amyloid Production (Fri, 11 Feb 2011)
<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="19.30mm" wi="57.66mm" file="US20110034513A1-20110210-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, R<sub>6</sub>, T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's disease and Down's syndrome are described.</p>
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Glycopeptide antibiotics (Thu, 06 Jan 2011)
The invention provides compounds of formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6a , R 6b , R 6c , R 6d , R 6e and R 7 are defined in the specification. These compounds are useful as antibiotic agents.
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IMMUNOGENIC COMPOSITIONS OF STAPHYLOCOCCUS AUREUS ANTIGENS (Thu, 30 Dec 2010)
The present invention relates to immunogenic compositions, comprising polypeptides and polysaccharides from Staphylococcus aureus. The present invention also relates to immunogenic compositions, comprising Staphylococcus aureus capsule polysaccharides conjugated to a carrier protein. In addition, the invention relates to methods of inducing an immune response in subjects against Staphylococcus aureus using immunogenic compositions of the Staphylococcus aureus polypeptides and capsule polysaccharides.
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IMMUNOGENIC COMPOSITIONS OF STAPHYLOCOCCUS AUREUS ANTIGENS (Thu, 30 Dec 2010)
The present invention relates to immunogenic compositions, comprising polypeptides and polysaccharides from Staphylococcus aureus. The present invention also relates to immunogenic compositions, comprising Staphylococcus aureus capsule polysaccharides conjugated to a carrier protein. In addition, the invention relates to methods of inducing an immune response in subjects against Staphylococcus aureus using immunogenic compositions of the Staphylococcus aureus polypeptides and capsule polysaccharides.</p>
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Crystalline forms of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile and methods of preparing the same (Fri, 24 Dec 2010)
<p id="p-0001" num="0000">This invention is directed to a crystalline 4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-methyl-1-piperazinyl)propoxy]-3-quinolinecarbonitrile monohydrate having an x-ray diffraction pattern wherein 2θ angles (°) of significant peaks are at about: 9.19, 11.48, 14.32, 19.16, 19.45, 20.46, 21.29, 22.33, 23.96, 24.95, 25.29, 25.84, 26.55, 27.61, and 29.51, and a transition temperature of about 109° C. to about 115° C.</p>
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Amino-imidazolones for the inhibition of beta-secretase (Thu, 23 Dec 2010)
The present invention provides an amino-imidazolone compound of formula (I): Also provided are compositions and methods for the use thereof to inhibit ²-secretase (BACE) and treat ²-amyloid deposits and neurofibrillary tangles.
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Multivalent pneumococcal polysaccharide-protein conjugate composition (Fri, 17 Dec 2010)
<p id="p-0001" num="0000">An immunogenic composition having 13 distinct polysaccharide-protein conjugates and optionally, an aluminum-based adjuvant, is described. Each conjugate contains a capsular polysaccharide prepared from a different serotype of <i>Streptococcus pneumoniae </i>(1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) conjugated to a carrier protein. The immunogenic composition, formulated as a vaccine, increases coverage against pneumococcal disease in infants and young children globally, and provides coverage for serotypes 6A and 19A that is not dependent on the limitations of serogroup cross-protection. Also described is a method for making an immunogenic conjugate comprising <i>Streptococcus pneumoniae </i>serotype 3 polysaccharide covalently linked to a carrier protein, the method including periodic acid oxidation of the polysaccharide in the presence of bivalent cations.</p>
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Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof (Thu, 09 Dec 2010)
The present invention relates to maleate salt forms of (E)-N-14-[3-chloro-4-(2-pyridinylmethoxy]anilino}-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide, methods of preparing crystalline maleate salt forms, the associated compounds, and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family.
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SUBSTITUTED IMIDAZO[1,5-a]QUINOXALINES AS INHIBITORS OF PHOSPHODIESTERASE 10 (Fri, 03 Dec 2010)
The invention relates to imidazo[1,5-a]quinoxaline derivatives which are inhibitors of phosphodiesterase 10 (PDE10) useful in treating central nervous system diseases such as psychosis and also in treating, for example, obesity, type 2 diabetes, metabolic syndrome, glucose intolerance, and pain.
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Amino-5-[4-(difluoromethoxy)phenyl]-5-phenylimidazolone compounds as inhibitors of the beta-secretase (BACE) (Thu, 02 Dec 2010)
The present invention provides a 2-amino-5-[4-(difluoromethoxy)phenyl]-5-3,-dihydrophenylimidazol-4-one compound of formula (I): The present invention also provides methods for the use thereof to inhibit ²-secretase (BACE) and treat ²-amyloid deposits and neutrofibrillary tangles.
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SUBSTITUTED 3-CYANOQUINOLINES AS PROTEIN TYROSINE KINASES INHIBITORS (Thu, 25 Nov 2010)
This invention provides compounds of formula 1 wherein R 1 , G 1 , G 2 , R 4 , Z, X and n are defined herein, or a pharmaceutically acceptable salt thereof, which are useful as antineoplastic agents and in the treatment of polycystic kidney disease.
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Inhibitors of cytosolic phospholipase a2 (Thu, 11 Nov 2010)
This invention provides chemical inhibitors of the activity of various phospholipase enzymes, particularly cytosolic phospholipase A 2 enzymes (cPLA 2 ). Of particular interest is 4-(3-{5-chloro-1-(diphenylmethyl)-2-[2-({[2-(trifluoromethyl)benzy]sulfonyl}amino)ethyl]-1 H -indol-3-yl}propyl) benzoic acid, or a pharmaceutically acceptable salt thereof. The compounds of the invention are indicated, inter alia, in the treatment of inflammation.
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Bisaryl Alkynylamides as Negative Allosteric Modulators of Metabotropic Glutamate Receptor 5 (MGLUR5) (Fri, 29 Oct 2010)
<p id="p-0001-en" num="0000">Disclosed are compounds of Formula I:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="40.22mm" wi="73.58mm" file="US20100273772A1-20101028-C00001.TIF" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">pharmaceutical compositions containing compounds of Formula I, and the use of compounds of Formula I to treat diseases and disorders including schizophrenia, paranoia, depression, manic-depressive illness and anxiety wherein W<sup>1</sup>-W<sup>5</sup>, X<sup>1</sup>-X<sup>4</sup>, Y, Z<sup>1</sup>-Z<sup>5</sup>, m, n, p, and R<sup>1</sup>-R<sup>6 </sup>in Formula I are defined in the specification.</p>
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BISARYL ALKYNYLAMIDES AS NEGATIVE ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 5 (MGLUR5) (Fri, 29 Oct 2010)
Disclosed are compounds of Formula (I): pharmaceutical compositions containing compounds of Formula I, and the use of compounds of Formula (I) to treat diseases and disorders including schizophrenia, paranoia, depression, manic-depressive illness and anxiety wherein W1-W5, X1-X4, Y, Z1-Z5, m, n, p, and R1-R6 in Formula (I) are defined in the specification.
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UREIDOARYL-AND CARBAMOYLARYL-MORPHOLINO- PYRIMIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESIS (Fri, 22 Oct 2010)
The invention relates to ureidophenyl-morpholino pyrimidine and guanidinophenyl-morpholino pyrimidine compounds of formula, and to methods for making and using the compounds.
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Carbamate compounds which inhibit leukocyte adhesion mediated by VLA-4 (Fri, 15 Oct 2010)
<p id="p-0001" num="0000">Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.</p>
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FORMULATIONS FOR PARENTERAL DELIVERY OF COMPOUNDS AND USES THEREOF (Fri, 01 Oct 2010)
<p id="p-0001-en" num="0000">The present invention provides formulations that achieve effective delivery of methylnaltrexone compositions. The provided formulations are useful for preventing, treating delaying, diminishing or reducing the severity of side effects resulting from use of analgesic opioids.</p>
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SYNTHESIS OF PYRROLIDINE COMPOUNDS (Fri, 01 Oct 2010)
<p id="p-0001-en" num="0000">Provided are methods for the preparation of certain substituted pyrrolidine compounds, forms of (2S,4R)-1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid hydrochloride, and methods for preparing and using these forms.</p>
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METHODS FOR THE PREPARATION OF [2-(8,9-DIOXO-2,6-DIAZABICYCLO[5.2.0]NON-1(7)-EN-2-YL)ETHYL]PHOSPHONIC ACID AND PRECURSORS THEREOF (Fri, 24 Sep 2010)
The present invention is directed to processes associated with the preparation of [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid (perzinfotel).
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METHODS FOR THE PREPARATION OF [2-(8,9-DIOXO-2,6-DIAZABICYCLO[5.2.0]NON-1(7)-EN-2-YL)ETHYL]PHOSPHONIC ACID AND PRECURSORS THEREOF (Fri, 24 Sep 2010)
The present invention is directed to processes associated with the preparation of [2-(8,9-dioxo-2,6- diazabicyclo[5.2.0]non-1(7)-en-2-yl)ethyl]phosphonic acid (perzinfotel). </p>
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POLYMORPHS OF N2-(1,1'-BIPHENYL-4-YLCARBONYL)-N1-[2-(4-FLUOROPHENYL)-1,1-DIMETHYLETHYL]-L-ALPHA-GLUTAMINE (Fri, 27 Aug 2010)
<p id="p-0001-en" num="0000">Disclosed are novel polymorphic forms of N<sup>2</sup>-(1,1′-biphenyl-4-ylcarbonyl)-N<sup>1</sup>-[2-(4-fluorophenyl)-1,1-dimethylethyl]-L-α-glutamine, methods of preparing the polymorphic forms, compositions containing the polymorphic forms, and methods of treatment using the polymorphic forms.</p>
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Humanized antibodies that recognize beta amyloid peptide (Thu, 26 Aug 2010)
The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of A² in the brain of a patient. Preferred agents include humanized antibodies.
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Amino-pyridines As Inhibitors Of Beta-secretase (Fri, 13 Aug 2010)
<p id="p-0001-en" num="0000">The present invention provides an amino-pyridine compound of formula I</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.</p>
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SUBSTITUTED OXINDOLE CB2 AGONISTS (Fri, 13 Aug 2010)
Provided are substituted compounds, or pharmaceutically acceptable salts thereof, wherein: R1 is selected from -(CH2)nRa, -CH(OH)Ra, -CH(ORb)Ra, and -C(O)Ra, or is selected from ORa, SRa, SORa, SO2Ra and NRaRb; R2 and R3 are independently selected from H, halogen, OH, ORa, OWRa, C1-6 alkyl, and WC 1-6 alkyl, wherein C1-6 alkyl or ORa, is optionally substituted with 1, 2, or 3 substitutents independently selected from halogen, CN, OH, ORa, C1-6 alkyl, C1-6 haloalkyl, C3-8cycloalkyl, C6-10 aryl and C4-10 heteroaryl; or R2 and R3, together with the carbon atom to which they are attached, join to form a ring selected from 3-8 membered cycloalkyl, 3-8 membered heterocycloalkyl, C5-C7 oxycycloalkyl, C5.7 dioxycycloalkyl and oxazolidinyl ring, each ring optionally substituted with 1, 2, or 3 substituents independently selected from halogen, CN, OH, 0Ra, C1-6alkyl, C1-6 haloalkyl, C3-8 cycloalkyl, C6-10aryl and C4-10 heteroaryl; R4 is independently selected from H.C1-6 alkyl, C2-6 alkenyl, C2-6alkynyl, C6-10 aryl, C4-10 heteroaryl, -(CH2)n-benzodioxane, -(CH2)n- oxazolidinone and -(CH2)n-C1-6 haloalkyl, each of which is optionally substituted with 1, 2, or 3 substitutents independently selected from halogen, CN, OH, ORa, C1-6 alkyl, C1-6 haloalkyl, C3.8 cycloalkyl, WC3.8 cycloalkyl, C6-10 aryl and C4.10 heteroaryl; which are agonists of the CB2 receptor, pharmaceutical compositions containing the same, and methods of treatment related to CB2-mediated disorders (eg., pain, cancer etc.) using the substituted oxindole compounds and compositions described herein.
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Immunophilin Ligands and Methods for Modulating Immunophilin and Calcium Channel Activity (Fri, 06 Aug 2010)
<p id="p-0001-en" num="0000">Immunophilin ligands and their uses as modulators of calcium channel activity are disclosed. Screening, therapeutic and prophylactic methods for conditions associated with calcium channel dysfunction, e.g., neurodegenerative and cardiovascular disorders, are also disclosed.</p>
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PROCESS FOR PREPARING QUINOLINE COMPOUNDS AND PRODUCTS OBTAINED THEREFROM (Fri, 06 Aug 2010)
<p id="p-0001-en" num="0000">Methods for synthesizing tetrahydroquinoline-containing compounds are provided, along with synthetic intermediates and products associated with such methods.</p>
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Thioamide derivatives as progesterone receptor modulators (Fri, 06 Aug 2010)
<p id="p-0001" num="0000">Thioamide compounds, and specifically, thioamide pyrrole compounds, and preparation thereof are provided. These thioamide compounds can be used as progesterone receptor modulators, in contraception, and in the treatment of progesterone-related maladies.</p>
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Polar Quinazolines (Fri, 23 Jul 2010)
<p id="p-0001-en" num="0000">Disclosed are polar quinazoline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I):</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="27.43mm" wi="55.54mm" file="US20100184786A1-20100722-C00001.TIF" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">in which, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, R<sup>22</sup>, R<sup>23</sup>, R<sup>24</sup>, R<sup>25</sup>, R<sup>26</sup>, R<sup>27</sup>, R<sup>28</sup>, R<sup>29</sup>, W, W<sup>1</sup>, W<sup>2</sup>, R<sup>a</sup>, R<sup>b</sup>, R<sup>c</sup>, R<sup>d</sup>, R<sup>e</sup>, R<sup>f</sup>, R<sup>g</sup>, R<sup>h</sup>, R<sup>i</sup>, R<sup>j</sup>, R<sup>m</sup>, R<sup>n</sup>, R<sup>o</sup>, R<sup>p</sup>, R<sup>q</sup>, R<sup>r</sup>, R<sup>s</sup>, R<sup>t</sup>, R<sup>u</sup>, and n can be as defined anywhere herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs.</p>
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SUBSTITUTED OXINDOL CB2 AGONISTS FOR PAIN TREATMENT (Fri, 09 Jul 2010)
Provided are 3-substituted oxindole derivatives which are agonists of the CB2 receptor, pharmaceutical compositions containing the same, and methods of treatment related to CB2-mediated disorders (e.g., pain, cancer etc.) using the 3-substituted oxindole derivatives and compositions described herein.
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Imidazole Amines As Inhibitors Of Beta-secretase (Fri, 02 Jul 2010)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I and the use thereof for the therapeutic treatment, prevention or amelioration of a disease or disorder characterized by elevated 3-amyloid deposits or 3-amyloid levels in a patient.</p> <p id="p-0002-en" num="0000"/>
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Amino-5-(5-membered)heteroarylimidazolone Compounds And The Use Thereof For Beta-secretase Modulation (Fri, 02 Jul 2010)
<p id="p-0001-en" num="0000">The present invention provides a 2-amino-5-heteroaryl-5-phenylimidazolone compound of formula I</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles</p>
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Amino-5-[4-(difluoromethoxy)phenyl]-5-phenylimidazolone Compounds For The Inhibition Of Beta-secretase (Fri, 02 Jul 2010)
<p id="p-0001-en" num="0000">The present invention provides compounds and methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.</p>
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Expression of the cysteine protease legumain in vascular and inflammatory diseases (Fri, 25 Jun 2010)
<p id="p-0001-en" num="0000">The present invention provides isolated and purified polynucleotides, polypeptides, and antibodies related to mammalian (e.g., mouse and human) legumain and the novel legumain splice variant, ZB-1. The invention further relates to the use of these isolated and purified polynucleotides, polypeptides, and antibodies, as well as other legumain and ZB-1 agonists and antagonists, in modulating legumain and/or ZB-1 activity, expression, and/or secretion in a cell or cell population, e.g., monocytes, macrophages, foam cells, vascular endothelial cells, kidney proximal tubule cells, arterial endothelial cells, sites of inflammatory cell invasion into a vessel intima, and neointimal lesional areas of an artery. The invention also provides legumain and ZB-1 antagonists, e.g., antagonistic small molecules, antibodies and antibody fragments to legumain and ZB-1, legumain and ZB-1 inhibitory polypeptides, and legumain and ZB-1 inhibitory polynucleotides. The present invention is also directed to novel methods for diagnosing, prognosing, monitoring, treating, ameliorating and/or preventing vascular disorders/diseases and inflammatory disorders/diseases.</p>
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Heteroaryl, heterocyclic and aryl compounds which inhibit leukocyte adhesion mediated by VLA-4 (Fri, 25 Jun 2010)
<p id="p-0001" num="0000">Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.</p>
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Heteroaryl, heterocyclic and aryl compounds which inhibit leukocyte adhesion mediated by VLA-4 (Fri, 25 Jun 2010)
<p id="p-0001" num="0000">Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.</p>
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BENZOXATHIINE AND BENZOXATHIOLE DERIVATIVES AND USES THEREOF (Fri, 25 Jun 2010)
<p id="p-0001-en" num="0000">Compounds of formula (I) or pharmaceutically acceptable salts thereof are provided, wherein each of R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, y, n, m, p, and Ar are as defined, and described in classes and subclasses herein, which are agonists or partial agonists of the 2C subtype of brain serotonin receptors. The compounds, and compositions containing the compounds, can be used to treat a variety of central nervous system disorders such as schizophrenia.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="28.70mm" wi="61.47mm" file="US20100160411A1-20100624-C00001.TIF" img-content="chem" img-format="tif"/> </chemistry> </p>
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HUMANIZED ANTI-RAGE ANTIBODY (Fri, 11 Jun 2010)
<p id="p-0001-en" num="0000">Compositions comprising antigen binding polypeptides that bind specifically to Receptor For Advanced Glycation End-product (RAGE) and comprises: one or more complementarity determining regions (CDRs) with improved binding efficiency over a parental monoclonal antibody to RAGE are described. Antibodies containing the CDR's and methods of treating a RAGE-related disease or disorder comprising administering to the subject a therapeutically effective amount of the compositions of the invention are also provided.</p>
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Heterocyclic Sulfonamide Inhibitors of Beta Amyloid Production Containing an Azole (Fri, 11 Jun 2010)
<p id="p-0001-en" num="0000">Compounds useful for lowering beta amyloid levels are provided. The compounds have the structure of formula Ia:</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">wherein, R<sub>1 </sub>is lower alkyl, substituted lower alkyl, phenyl, substituted phenyl, benzyl, substituted benzyl, benzyloxy, substituted benzyloxy, or SO<sub>2</sub>R<sub>5</sub>; R<sub>5 </sub>is phenyl, substituted phenyl, heterocycle, substituted heterocycle, alkyl, or substituted alkyl; R<sub>2 </sub>is lower alkyl, substituted lower alkyl, CF<sub>3</sub>, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, or cycloalkyl; R<sub>3 </sub>is hydrogen, lower alkyl, or substituted lower alkyl; R<sub>4 </sub>is phenyl, substituted phenyl, heterocycle, substituted heterocycle, thiophene, or substituted thiophene; R<sub>6 </sub>is hydrogen, lower alkyl, substituted lower alkyl, CF<sub>3</sub>, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, cycloalkyl, or substituted cycloalkyl; W, X and Y are independently CR<sub>7 </sub>or N; and R<sub>7 </sub>is hydrogen, halogen, lower alkyl, or substituted lower alkyl.</p>
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Biaryl Sulfonamides and Methods for Using Same (Fri, 04 Jun 2010)
<p id="p-0001-en" num="0000">The present invention relates to biaryl sulfonamides and their use as, for example, metalloproteinase inhibitors.</p>
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Antibodies against human interleukin-13 and uses therefor (Fri, 28 May 2010)
<p id="p-0001" num="0000">This application relates to antibodies, e.g., humanized antibodies, and antigen-binding fragments thereof, that bind to interleukin-13 (IL-13), in particular, human IL-13, and their uses in regulating immune responses mediated by IL-13. The antibodies disclosed herein are useful in diagnosing, preventing, and/or treating a subject, e.g., a human patient, one or more IL-13-associated disorders, e.g., respiratory disorders (e.g., asthma); atopic disorders (e.g., allergic rhinitis); inflammatory and/or autoimmune conditions of the skin (e.g., atopic dermatitis), and gastrointestinal organs (e.g., inflammatory bowel diseases (IBD)), as well as fibrotic and cancerous disorders.</p>
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ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS (Fri, 28 May 2010)
<p id="p-0001-en" num="0000">The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory systems.</p>
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POLAR QUINAZOLINES AS LIVER X RECEPTORS ( LXRS ) MODULATORS (Fri, 28 May 2010)
Disclosed are polar quinazoline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I): INSERT FORMULA HERE AS IT APPEARS IN WRITTEN FORM IN THE SPECIFICATION (I) in which, R1, R2, R3, R4, R5, R6, R22, R23, R24, R25, R26, R27, R28, R29, W, W1, W2, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, Ri, Rj, Rm, Rn, Ro, Rp, Rq, Rr, Rs, Rt, Ru, and n can be as defined anywhere herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs.
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POLAR QUINAZOLINES AS LIVER X RECEPTORS ( LXRS ) MODULATORS (Fri, 28 May 2010)
Disclosed are polar quinazoline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I): INSERT FORMULA HERE AS IT APPEARS IN WRITTEN FORM IN THE SPECIFICATION (I) in which, R1, R2, R3, R4, R5, R6, R22, R23, R24, R25, R26, R27, R28, R29, W, W1, W2, Ra, Rb, Rc, Rd, Re, Rf, Rg, Rh, Ri, Rj, Rm, Rn, Ro, Rp, Rq, Rr, Rs, Rt, Ru, and n can be as defined anywhere herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs. </p>
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1-(ARYLSULFONYL)-4-(PIPERAZIN-1-YL)-1H-BENZIMIDAZOLES AS 5-HYDROXYTRYPTAMINE-6 LIGANDS (Fri, 21 May 2010)
The invention relates to 1-(arylsulfonyl)-4-(piperazin-1-yl)-1H-benzimidazole compounds of the Formula I: or a tautomer, stereoisomer, or pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
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1-(ARYLSULFONYL)-4-(PIPERAZIN-1-YL)-1H-BENZIMIDAZOLES AS 5-HYDROXYTRYPTAMINE-6 LIGANDS (Fri, 21 May 2010)
The invention relates to 1-(arylsulfonyl)-4-(piperazin-1- yl)-1H-benzimidazole compounds of the Formula I: or a tautomer, stereoisomer, or pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds. </p>
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IMIDAZO[5,1-C][1,2,4]BENZOTRIAZINE DERIVATIVES AS INHIBITORS OF PHOSPHODIESTERASES (Sat, 15 May 2010)
The invention relates to imidazo[5,1-c][1,2,4]benzotriazine derivatives of formula (I): which are inhibitors of phosphodiesterase 2 or 10 useful in treating central nervous system diseases such as psychosis and also in treating, for example, obesity, type 2 diabetes, metabolic syndrome, glucose intolerance, and pain.
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QUINOXALINE-BASED LXR MODULATORS (Sat, 15 May 2010)
Disclosed are quinoxaline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I): wherein: each of L1 and L2 is, independently, a bond, -O- or -NH-; R2 is C6-C10 aryl or heteroaryl including 5-10 ring atoms, each of which is (i) substituted with 1 R9, and (ii) optionally further substituted with from 1-4 Re; and each of R4 and R5 is, independently (i) hydrogen; or (ii) halo; or (iii) C1-C6 alkyl or C1-C6 haloalkyl, each of which is optionally substituted with from 1-3 Ra; and R1, R3, R6, R9, Ra and Re are defined herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs.
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QUINOXALINE-BASED LXR MODULATORS (Sat, 15 May 2010)
Disclosed are quinoxaline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I): wherein: each of L1 and L2 is, independently, a bond, -O- or -NH-; R2 is C6-C10 aryl or heteroaryl including 5-10 ring atoms, each of which is (i) substituted with 1 R9, and (ii) optionally further substituted with from 1-4 Re; and each of R4 and R5 is, independently (i) hydrogen; or (ii) halo; or (iii) C1-C6 alkyl or C1-C6 haloalkyl, each of which is optionally substituted with from 1-3 Ra; and R1, R3, R6, R9, Ra and Re are defined herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs. </p>
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1-(arylsulfonyl)-4-(piperazin-1-yl)-1H-benzimidazoles as 5-hydroxytryptamine-6 ligands (Fri, 14 May 2010)
<p id="p-0001" num="0000">The invention relates to 1-(arylsulfonyl)-4-(piperazin-1-yl)-1H-benzimidazole compounds of the Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="65.19mm" wi="69.85mm" file="US08063053-20111122-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or a tautomer, stereoisomer, or pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds. </p>
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QUINOXALINE-BASED LXR MODULATORS (Fri, 14 May 2010)
<p id="p-0001-en" num="0000">Disclosed are quinoxaline-based modulators of Liver X receptors (LXRs) and related methods. The modulators include compounds of formula (I):</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">wherein: <ul id="ul0001-en" list-style="none"><li><ul id="ul0002-en" list-style="none"><li>each of L<sup>1 </sup>and L<sup>2 </sup>is, independently, a bond, —O— or —NH—;</li><li>R<sup>2 </sup>is C<sub>6</sub>-C<sub>10 </sub>aryl or heteroaryl including 5-10 atoms, each of which is (i) substituted with 1 R<sup>9</sup>, and (ii) optionally further substituted with from 1-4 R<sup>e</sup>; and</li><li>each of R<sup>4 </sup>and R<sup>5 </sup>is, independently (i) hydrogen; or (ii) halo; or (iii) C<sub>1</sub>-C<sub>6 </sub>alkyl or C<sub>1</sub>-C<sub>6 </sub>haloalkyl, each of which is optionally substituted with from 1-3 R<sup>a</sup>;</li><li>and R<sup>1</sup>, R<sup>3</sup>, R<sup>6</sup>, R<sup>9</sup>, R<sup>a </sup>and R<sup>e </sup>are defined herein. In general, these compounds can be used for treating or preventing one or more diseases, disorders, conditions or symptoms mediated by LXRs.</li></ul></li></ul></p>
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IMIDAZO[5,1-C][1,2,4]BENZOTRIAZINE DERIVATIVES AS INHIBITORS OF PHOSPHODIESTERASES (Fri, 14 May 2010)
<p id="p-0001-en" num="0000">The invention relates to imidazo[5,1-c][1,2,4]benzotriazine derivatives of formula I:</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">which are inhibitors of phosphodiesterase 2 or 10 useful in treating central nervous system diseases such as psychosis and also in treating, for example, obesity, type 2 diabetes, metabolic syndrome, glucose intolerance, and pain.</p>
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Peripheral opioid receptor antagonists and uses thereof (Fri, 14 May 2010)
<p id="p-0001" num="0000">The present invention provides a compound of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="33.95mm" wi="53.59mm" file="US08247425-20120821-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein X<sup>−</sup>, R<sup>1</sup>, and R<sup>2 </sup>are as defined herein, and compositions thereof. </p>
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Carbamate compounds which inhibit leukocyte adhesion mediated by VLA-4 (Fri, 07 May 2010)
<p id="p-0001" num="0000">Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a mammalian patient, e.g., human, such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.</p>
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IMPROVED PROCESS FOR PREPARATION OF COUPLED PRODUCTS FROM 4-AMINO-3-CYANOQUINOLINES USING STABILIZED INTERMEDIATES (Fri, 30 Apr 2010)
This invention discloses improved methods for coupling a 4-(amino)-2-butenoyl group to an amino group at the 6- or 7-position of a 4-amino-3-quinolinecarbonitrile by generating a stabilized 4-(amino)-2-butenoyl chloride hydrochloride.
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Peripheral opioid receptor antagonists and uses thereof (Fri, 23 Apr 2010)
<p id="p-0001" num="0000">The present invention provides a compound of formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="34.46mm" wi="53.59mm" file="US08338446-20121225-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein X<sup>−</sup>, R<sup>1</sup>, and R<sup>2 </sup>are as defined herein, and compositions thereof, useful as a peripheral mu opioid receptor antagonist. </p>
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PERIPHERAL OPIOID RECEPTOR ANTAGONISTS AND USES THEREOF (Fri, 09 Apr 2010)
The present invention provides a compound of formula I wherein X", R1, and R2 are as defined herein, and compositions thereof. The compounds include and are based on an impurity of methylnaltrexone, a peripheral opioid antagonist.
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GITR LIGAND AND GITR LIGAND-RELATED MOLECULES AND ANTIBODIES AND USES THEREOF (Fri, 02 Apr 2010)
<p id="p-0001-en" num="0000">The present invention provides novel isolated and purified polynucleotides and polypeptides related to a novel ligand for glucocorticoid-induced TNF receptor (GITR). The invention also provides antibodies to the GITR ligand (GITRL). The present invention also is directed to novel methods for diagnosing, prognosing, monitoring the progress of, and treating disorders arising from disregulation of the immune system (e.g., autoimmune disorders, inflammatory diseases, and transplant rejection, and cancers and infectious diseases) using GITRL and/or modulators of GITRL. The present invention is further directed to novel therapeutics and therapeutic targets and to methods of screening and assessing test compounds for the intervention (treatment) and prevention of said disorders arising from disregulation of the immune system, as related to GITRL and GITR.</p>
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4-ARYLOXYQUINOLIN-2(1H)-ONES AS MTOR KINASE AND PI3 KINASE INHIBITORS, FOR USE AS ANTI-CANCER AGENTS (Fri, 19 Mar 2010)
<p id="p-0001-en" num="0000">Compounds of the formula I</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="44.37mm" wi="59.35mm" file="us20100068204a1-20100318-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">and pharmaceutically acceptable salts thereof, wherein A, B, R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, R<sup>6</sup>, and R<sup>7 </sup>are defined as set forth herein are disclosed. Also disclosed are pharmaceutical compositions comprising the compounds of the invention and a pharmaceutically acceptable carrier, methods of making the compounds of the invention and methods of using the compounds for inhibiting mTOR and PI3 kinases and for treating cancers.</p>
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3-SUBSTITUTED-1H-INDOLE, 3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 19 Mar 2010)
The invention relates to 3-substituted-1H-indole, 3-substituted-1H-pyrrolo[2,3-b]pyridine, and 3-substituted-1H-pyrrolo[3,2-b]pyridine compounds of the Formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
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4-ARYLOXYQUINOLIN-2(1H)-ONES AS MTOR KINASE AND PI3 KINASE INHIBITORS, FOR USE AS ANTI-CANCER AGENTS (Fri, 19 Mar 2010)
4-aryloxyquinolin-2(1H)-ones as mtor kinase and PI3 kinase inhibitors, for use as anti-cancer agents. Compounds of the formula I and pharmaceutically acceptable salts thereof, wherein A, B, R1, R2, R3, R4, R5, R6, and R7 are defined as set forth herein are disclosed. Also disclosed are pharmaceutical compositions comprising the compounds of the invention and a pharmaceutically acceptable carrier, methods of making the compounds of the invention and methods of using the compounds for inhibiting mTOR and PI3 kinases and for treating cancers.
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3-SUBSTITUTED-1H-INDOLE, 3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 12 Mar 2010)
<p id="p-0001-en" num="0000">The invention relates to 3-substituted-1H-indole, 3-substituted-1H-pyrrolo[2,3-b]pyridine, and 3-substituted-1H-pyrrolo[3,2-b]pyridine compounds of the Formula 1:</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.</p>
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Bicyclic and Tricyclic Substituted 6-Methylidene Carbapenems as Broad Spectrum Beta-Lactamase Inhibitors (Fri, 12 Mar 2010)
<p id="p-0001-en" num="0000">Provided is a β-lactamase antibiotic and a compound of formula I, a process of producing the compound, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof.</p> <p id="p-0002-en" num="0000"/>
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6-SUBSTITUTED 2-(BENZIMIDAZOLYL)PURINE AND PURINONE DERIVATIVES AND 6-SUBSTITUTED 2-(IMIDAZOLO[4,5- C]PYRIDINYL)PURINE AND PURINONE DERIVATIVES FOR IMMUNOSUPPRESSION (Fri, 26 Feb 2010)
The present invention provides novel purinones and purines useful for the prevention and treatment of autoimmune diseases, inflammatory disease, mast cell mediated disease and transplant rejection. The compounds are of the genera formulae I and II wherein R1, R2, R3, R4, R9, Q, A and y are as defined in the specification.
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6-SUBSTITUTED 2-(BENZIMIDAZOLYL)PURINE AND PURINONE DERIVATIVES AND 6-SUBSTITUTED 2-(IMIDAZOLO[4,5- C]PYRIDINYL)PURINE AND PURINONE DERIVATIVES FOR IMMUNOSUPPRESSION (Fri, 26 Feb 2010)
The present invention provides novel purinones and purines useful for the prevention and treatment of autoimmune diseases, inflammatory disease, mast cell mediated disease and transplant rejection. The compounds are of the genera formulae I and II wherein R1, R2, R3, R4, R9, Q, A and y are as defined in the specification. </p>
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Oxazole, derivatives of tetracyclines (Thu, 25 Feb 2010)
This invention provides compounds of the formula: wherein A", X and Y are defined in the specification. These compounds are useful as antibacterial agents or may be hydrolysed to give 9-(2-substituted aminomethylcarbonylamino)substituted-6-demethyl-6-deoxytetracycline derivatives.
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HUMANIZED ANTI-RAGE ANTIBODY (Fri, 19 Feb 2010)
Compositions comprising antigen binding polypeptides that bind specifically to Receptor For Advanced Glycation End-product (RAGE) and comprises: one or more complementarity determining regions (CDRs) with improved binding efficiency over a parental monoclonal antibody to RAGE are described. Antibodies containing the CDR's and methods of treating a RAGE-related disease or disorder comprising administering to the subject a therapeutically effective amount of the compositions of the invention are also provided.
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Methods for the use of inhibitors of cytosolic phospholipase A2 (Fri, 12 Feb 2010)
<p id="p-0001" num="0000">This invention provides methods for the use of substituted indole compounds of the general formula:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="38.86mm" wi="73.07mm" file="US07906548-20110315-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and pharmaceutically acceptable salt forms thereof. The invention provides methods for the use of the compounds as inhibitors of the activity of various phospholipase enzymes, particularly phospholipase A<sub>2 </sub>enzymes, and for the medical treatment, prevention and inhibition diseases and disorders including asthma, stroke, atherosclerosis, multiple sclerosis, Parkinson's disease, arthritic disorders, rheumatic disorders, central nervous system damage resulting from stroke, central nervous system damage resulting from ischemia, central nervous system damage resulting from trauma, inflammation caused or potentiated by prostaglandins, inflammation caused or potentiated by leukotrienes, inflammation caused or potentiated by platelet activation factor, pain caused or potentiated by prostaglandins, pain caused or potentiated by leukotrienes, and pain caused or potentiated by platelet activation factor. </p>
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IDENTIFICATION AND CHARACTERIZATION OF HCV REPLICON VARIANTS WITH REDUCED SUSCEPTIBILITY TO BENZOFURANS, AND METHODS RELATED THERETO (Fri, 05 Feb 2010)
<p id="p-0001-en" num="0000">The present invention provides methods of decreasing the frequency of emergence, decreasing the level of resistance, and delaying the emergence of a treatment-resistant Hepatitis C viral infection, by administering to a subject, either in combination or in series, an inhibitor of the Hepatitis C RNA-dependent RNA polymerase NS5B, e.g., a benzofuran, such as 5-cyclopropyl-2-(4-fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-N-methyl-1-benzofuran-3-carboxamide (HCV-796), and at least one additional anti-Hepatitis C agent, e.g., a ribavirin product or an immunomodulator, such as an interferon product. Additionally, the invention relates to methods of monitoring the course of treatment of a Hepatitis C viral infection, methods of monitoring and prognosing a Hepatitis C viral infection, and methods of identifying an individual with a decreased likelihood of responding to an anti-Hepatitis C viral therapy. These methods use the sequence and/or structure of the Hepatitis C RNA-dependent RNA polymerase NS5B to identify the emergence of a treatment-resistant Hepatitis C viral infection, particularly a benzofuran (e.g., HCV-796) treatment-resistant Hepatitis C viral infection.</p>
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FERMENTATION AND PURIFICATION OF ACTINOMADURA CHROMOPROTEIN AND RELATED SPECIES (Fri, 05 Feb 2010)
<p id="p-0001-en" num="0000">The present invention provides methods for production and purification of active chromoproteins produced by <i>Actinomadura </i>sp. 21G792. The chromoproteins are useful for developing pharmaceutical compositions and treating diseases such as cancer or bacterial infections.</p>
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Modulators of α7 nicotinic acetylcholine receptors and therapeutic uses thereof (Fri, 05 Feb 2010)
<p id="p-0001" num="0000">The present invention provides compounds of formula (I) and compositions thereof, methods of making them, and methods of using them to modulate alpha7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="15.16mm" wi="69.85mm" file="US08163729-20120424-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Bridged, Bicyclic Heterocyclic or Spiro Bicyclic Heterocyclic Derivatives of Pyrazolo[1, 5-A]Pyrimidines, Methods for Preparation and Uses Thereof (Fri, 05 Feb 2010)
<p id="p-0001-en" num="0000">Compounds of formula A:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="25.57mm" wi="55.03mm" file="us20100029657a1-20100204-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">and pharmaceutically acceptable salts thereof are described, which selectively inhibit Raf kinase activity and are useful for treating disorders mediated by Raf kinases.</p>
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Process for Producing Anticancer Agent LL-D45042 (Fri, 29 Jan 2010)
<p id="p-0001-en" num="0000">The disclosure describes the production of anticancer agent LL-D45042, having the structure:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="63.33mm" wi="67.06mm" file="us20100022593a1-20100128-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">by fermentation, to methods for the recovery and concentration of this anticancer agent from crude solutions, and to processes for the purification of this anticancer agent as well as a new microorganism of the species <i>Streptomyces hygroscopicus </i>LL-D45042 and mutants thereof useful in the preparation of this compound.</p>
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Heterocyclic sulfonamide inhibitors of beta amyloid production (Fri, 29 Jan 2010)
<p id="p-0001-en" num="0000">Compounds of Formula (I),</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="19.13mm" wi="56.30mm" file="US07842718-20101130-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>3</sub>, R<sub>4</sub>, R<sub>5</sub>, R<sub>6</sub>, T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's disease and Down's syndrome are described. </p>
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BIOSYNTHETIC GENE CLUSTER FOR THE PRODUCTION OF A COMPLEX POLYKETIDE (Fri, 29 Jan 2010)
<p id="p-0001-en" num="0000">A polyketide synthase complex composed of polyketide synthase with 15 total modules, a non-ribosomal peptide synthetase with 1 module, and a cytochrome P450 hydroxylase is described. Also provided are novel <i>Streptomyces </i>species and methods of modified <i>Streptomyces </i>species. Further described are novel compounds, C-36-ketomeridamycin, C9-deoxomeridamycin, and C9-deoxoprolylmeridamcyin and uses thereof.</p>
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BIOSYNTHETIC GENE CLUSTER FOR THE PRODUCTION OF A COMPLEX POLYKETIDE (Fri, 29 Jan 2010)
A polyketide synthase complex composed of polyketide synthase with 15 total modules, a non-ribosomal peptide synthetase with 1 module, and a cytochrome P450 hydroxylase is described. Also provided are novel Streptomyces species and methods of modified Streptomyces species. Further described are novel compounds, C-36-ketomeridamycin, C9-deoxomeridamycin, and C9-deoxoprolylmeridamcyin and uses thereof.
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ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS (Fri, 22 Jan 2010)
<p id="p-0001-en" num="0000">The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.</p>
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ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS (Fri, 22 Jan 2010)
<p id="p-0001-en" num="0000">The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.</p>
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Indole acetic acids exhibiting CRTH2 receptor antagonism and uses thereof (Fri, 22 Jan 2010)
<p id="p-0001" num="0000">The invention relates to indole acetic acid compounds which function as antagonists of the CRTH2 receptor. The invention also relates to the use of these compounds to inhibit the binding of prostaglandin D<sub>2 </sub>and its metabolites or certain thromboxane metabolites to the CRTH2 receptor and to treat disorders responsive to such inhibition.</p>
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ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS (Fri, 22 Jan 2010)
<p id="p-0001-en" num="0000">The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.</p>
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METHODS FOR THE PREPARATION OF AZOLE COMPOUNDS (Fri, 22 Jan 2010)
<p id="p-0001-en" num="0000">The present invention is directed to processes, compositions and methods associated with the preparation of azole derivatives of formula I:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="24.30mm" wi="63.16mm" file="us20100016609a1-20100121-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS (Fri, 22 Jan 2010)
The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory systems.
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METHODS FOR THE PREPARATION OF AZOLE COMPOUNDS (Fri, 22 Jan 2010)
The present invention is directed to processes, compositions and methods associated with the preparation of azole derivatives of formula I
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ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR INHIBITORS (Fri, 22 Jan 2010)
The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate .alpha.7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Pro-vided compounds can affect, among other things, neurological, psychiatric and/or inflammatory systems. </p>
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(2-ARYL-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)MORPHOLINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 08 Jan 2010)
<p id="p-0001-en" num="0000">The invention relates to 2-aryl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)morpholine compounds of the Formula I:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="37.00mm" wi="59.01mm" file="us20100003250a1-20100107-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001-en" list-style="none"> <li> <ul id="ul0002-en" list-style="none"> <li>or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.</li> </ul> </li> </ul> </p>
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(2-ARYL-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)MORPHOLINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 08 Jan 2010)
The invention relates to 2-aryl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)morpholine compounds of the Formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
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PERIPHERAL OPIOID RECEPTOR ANTAGONISTS AND USES THEREOF (Thu, 07 Jan 2010)
The present invention provides a compound of formula I wherein X<sp>-</sp>, R<sp>1</sp>, and R<sp>2 </sp>are as defined herein, and compositions thereof, useful as a peripheral mu opioid receptor antagonist.
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1-SUBSTITUTED-3-(NAPHTHALEN-1-YLSULFONYL)-5-(PIPERAZIN-1-YL)-1H-INDAZOLE COMPOUNDS AS 5-HYDROXYTRYPTAMINE-6 LIGANDS (Fri, 25 Dec 2009)
<p id="p-0001-en" num="0000">The disclosure is directed to compounds of Formula I:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="40.89mm" wi="64.26mm" file="us20090318470a1-20091224-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">processes for their preparation, treatment of central nervous system (CNS) disorders and methods for the modulation of 5HT<sub>6 </sub>activity.</p>
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1-SUBSTITUTED-3-(NAPHTHALEN-1-YLSULFONYL)-5-(PIPERAZIN-1-YL)-1H-INDAZOLE COMPOUNDS AS 5-HYDROXYTRYPTAMINE-6 LIGANDS (Thu, 24 Dec 2009)
The disclosure is directed to compounds of Formula I, processes for their preparation, treatment of central nervous system (CNS) disorders and methods for the modulation of 5HT6 activity.
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THIENYL- AND FURANYL-ISOQUINOLINONES AND METHODS FOR USING THEM (Thu, 24 Dec 2009)
The present invention relates to substituted thienyl- and furanyl- isoquinolinones that act, for example, as modulators of poly(ADP-ribose) polymerase (PARP). The present invention also relates to processes for the preparation of substituted thienyl and furanyl-isoquinolinones and to their use in treating various diseases and disorders.
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3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Thu, 24 Dec 2009)
The invention relates to 3-substituted-1 H-pyrrolo[2,3-b]pyridine, and 3-substituted-1 H- pyrrolo[3,2-b]pyridine compounds of the Formula 1: or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds for the treatment of PI3 and mTOR kinase-mediated diseases, e.g. cancer.
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3-SUBSTITUTED-1H-INDOLE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Thu, 24 Dec 2009)
The invention relates to 3-substituted-1 H-indole compounds of the Formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds for the treatment of PI3 and mTOR kinase-mediated diseases, e.g. cancer.
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THIAZOLYL- AND OXAZOLYL-ISOQUINOLINONES AND METHODS FOR USING THEM (Thu, 24 Dec 2009)
The present invention relates to substituted thiazolyl- and oxazolyl- isoquinolinones that act, for example, as modulators of poly(ADP-ribose) polymerase (PARP). The present invention also relates to processes for the preparation of substituted thiazolyl- and oxazolyl- isoquinolinones and to their use in treating various diseases and disorders.
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3-SUBSTITUTED-1H-INDOLE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Thu, 24 Dec 2009)
The invention relates to 3-substituted-1H-indole compounds of the Formula (I): or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds for the treatment of PI3 and mTOR kinase- mediated diseases, e.g. cancer. </p>
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THIENYL- AND FURANYL-ISOQUINOLINONES AND METHODS FOR USING THEM (Thu, 24 Dec 2009)
The present invention relates to substituted thienyl- and furanyl- isoquinolinones that act, for example, as modulators of poly(ADP-ribose) polymerase (PARP). The present invention also relates to processes for the preparation of substituted thienyl and furanyl-isoquinolinones and to their use in treating various diseases and disorders. </p>
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THIAZOLYL- AND OXAZOLYL-ISOQUINOLINONES AND METHODS FOR USING THEM (Thu, 24 Dec 2009)
The present invention relates to substituted thiazolyl- and oxazolyl- isoquinolinones that act, for example, as modulators of poly(ADP-ribose) polymerase (PARP). The present invention also relates to processes for the preparation of substituted thiazolyl- and oxazolyl- isoquinolinones and to their use in treating various diseases and disorders. </p>
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3-SUBSTITUTED-1H-INDOLE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 18 Dec 2009)
<p id="p-0001-en" num="0000">The invention relates to 3-substituted-1H-indole compounds of the Formula I:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="35.39mm" wi="67.06mm" file="us20090311217a1-20091217-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.</p>
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Processes for the convergent synthesis of calicheamicin derivatives (Fri, 18 Dec 2009)
<p id="p-0001" num="0000">This invention describes processes for the convergent synthesis of calicheamicin derivatives, and similar analogs using bifunctional and trifunctional linker intermediates.</p>
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Therapeutic compositions and methods (Fri, 11 Dec 2009)
<p id="p-0001-en" num="0000">The present application provides novel binding proteins, including human binding proteins that specifically bind to the human ErbB2.</p>
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TRIAZINE COMPOUNDS AS PI3 KINASE AND MTOR INHIBITORS (Fri, 11 Dec 2009)
<p id="p-0001-en" num="0000">Compounds of formula I</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="21.84mm" wi="49.87mm" file="us20090304692a1-20091210-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001-en" list-style="none"> <li> <ul id="ul0002-en" list-style="none"> <li>wherein:</li> <li>R<sup>1 </sup>is</li> </ul> </li> </ul> </p> <p id="p-0003-en" num="0000"> <chemistry id="chem-us-00002-en" num="00002"> <img id="emi-c00002-en" he="24.13mm" wi="56.64mm" file="us20090304692a1-20091210-c00002.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0004-en" num="0000">and R<sup>2</sup>, R<sup>4</sup>, and R<sup>6-9 </sup>are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.</p>
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TANAPROGET DERIVATIVES, METABOLITES, AND USES THEREOF (Fri, 11 Dec 2009)
<p id="p-0001-en" num="0000">A method of generating synthetic metabolites of tanaproget derivatives thereof is provided. These compounds and methods of using these derivatives for detecting tanaproget metabolites in samples are provided.</p>
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Process for the synthesis of C-2, C-3 substituted N-alkylated indoles useful as cPLA<sub>2 </sub>inhibitors (Fri, 11 Dec 2009)
<p id="p-0001-en" num="0000">The present invention provides method for making a compound of formula 1:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="63.42mm" wi="71.97mm" file="US07842837-20101130-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> comprising the steps of reacting compounds of formulas 2 and 3: </p> <p id="p-0003-en" num="0000"> <chemistry id="chem-us-00002-en" num="00002"> <img id="emi-c00002-en" he="110.15mm" wi="56.73mm" file="US07842837-20101130-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> to produce a compound of formula 4: </p> <p id="p-0004-en" num="0000"> <chemistry id="chem-us-00003-en" num="00003"> <img id="emi-c00003-en" he="43.94mm" wi="74.93mm" file="US07842837-20101130-C00003.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4 </sup>and R<sup>5 </sup>are defined as described herein. The compound of formula 4 is then converted to the compound of formula 1. The invention further comprises compounds of formulas 3 and 4 and methods for making compounds of formulas 3 and 4. </p>
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3-SUBSTITUTED-1H-PYRROLO[2,3-B]PYRIDINE AND 3-SUBSTITUTED-1H-PYRROLO[3,2-B]PYRIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 04 Dec 2009)
<p id="p-0001-en" num="0000">The invention relates to 3-substituted-1H-pyrrolo[2,3-b]pyridine, and 3-substituted-1H-pyrrolo[3,2-b]pyridine compounds of the Formula 1:</p> <p id="p-0002-en" num="0000"> <ul id="ul0001-en" list-style="none"> <li> <ul id="ul0002-en" list-style="none"> <li>or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.</li> </ul> </li> </ul> </p>
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Triazine compounds as PI3 kinase and mTOR inhibitors (Fri, 27 Nov 2009)
<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="21.84mm" wi="49.61mm" file="US08039469-20111018-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001" list-style="none"> <li id="ul0001-0001" num="0000"> <ul id="ul0002" list-style="none"> <li id="ul0002-0001" num="0000">wherein:</li> <li id="ul0002-0002" num="0000">R<sup>1 </sup>is</li> </ul> </li> </ul> </p> <p id="p-0003" num="0000"><chemistry id="CHEM-US-00002" num="00002"> <img id="EMI-C00002" he="24.05mm" wi="55.37mm" file="US08039469-20111018-C00002.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> and R<sup>2</sup>, R<sup>4</sup>, and R<sup>6-9 </sup>are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed. </p>
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HETEROARYL ETHERS AND PROCESSES FOR THEIR PREPARATION (Fri, 27 Nov 2009)
<p id="p-0001-en" num="0000">The present invention relates to processes for the preparation of heteroaryl ethers. In some embodiments, the processes relate to cross coupling reactions between triazol-1-yloxy and triazol-1-yl heterocycles with aryl boronic acids. In a further aspect, this invention also relates to compounds that are useful for the treatment of oncological diseases or disorders, and for the treatment of inflammation.</p>
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TRIAZINE COMPOUNDS AS P13 KINASE AND MTOR INHIBITORS (Fri, 27 Nov 2009)
Compounds of formula I (I) wherein: R1 is (II) or (III); and R2, R4, and R6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.
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TRIAZINE COMPOUNDS AS P13 KINASE AND MTOR INHIBITORS (Fri, 27 Nov 2009)
Compounds of formula (I) wherein: R1 is and R2, R4, and R6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed.
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TRIAZINE COMPOUNDS AS PI3 KINASE AND MTOR INHIBITORS (Fri, 27 Nov 2009)
Compounds of formula (I) wherein: R1 is and R2, R4, and R6-9 are defined herein, and pharmaceutically acceptable salts and esters thereof. These compounds inhibit PI3 kinase and mTOR, and may be used to treat diseases mediated by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and using the compounds of this invention are disclosed. Various compositions containing the compounds of this invention are also disclosed. </p>
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TRIAZINE COMPOUNDS AS P13 KINASE AND MTOR INHIBITORS (Fri, 27 Nov 2009)
<br/><br/>Compounds of formula I(I) wherein: R1 is (II) or (III); and R2, R4, and R6-9 <br/>are defined herein, and pharmaceutically-acceptable <br/>salts and esters thereof. These compounds inhibit P13 kinase and mTOR, and may <br/>be used to treat diseases mediated <br/>by PI3 kinase and mTOR, such as a variety of cancers. Methods for making and <br/>using the compounds of this invention are disclosed.<br/>Various compositions containing the compounds of this invention are also <br/>disclosed.<br/><br/><br/><br/></p>
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BENZOFURAN COMPOUNDS, COMPOSITIONS AND METHODS FOR TREATMENT AND PROPHYLAXIS OF HEPATITIS C VIRAL INFECTIONS AND ASSOCIATED DISEASES (Thu, 19 Nov 2009)

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NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS (Thu, 19 Nov 2009)
The present invention provides compounds of formula (I) and compositions thereof, methods of making them, and methods of using them to modulate alpha7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.
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Cyclothiocarbamate derivatives as progesterone receptor modulators (Fri, 13 Nov 2009)
<p id="p-0001" num="0000">Methods of using compounds which are progesterone receptor agonists for contraception and the treatment of progesterone-related maladies alone or in combination with an estrogen receptor agonist or progesterone receptor antagonist are provided. These compounds have the structure:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="24.21mm" wi="32.51mm" file="US08329690-20121211-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein R<sup>1</sup>, R<sup>2</sup>, R<sup>3</sup>, R<sup>4</sup>, R<sup>5</sup>, and Q<sup>1 </sup>are defined herein. </p>
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Nucleic acids encoding IL-13 binding agents (Fri, 06 Nov 2009)
<p id="p-0001" num="0000">Agents (e.g., antibodies and fragments thereof) that bind specifically to IL 13 and modulate the ability of IL-13 to interact with IL-13 receptors and signaling mediators are disclosed.</p>
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3-Cyanoquinolines, Methods for Preparation and Use as Insulin-like Growth Factor Inhibitors (Fri, 23 Oct 2009)
<p id="p-0001-en" num="0000">Imidazole-substituted 4-anilino-3-cyanoquinolines are described, which selectively inhibit IFGR kinase activity and are useful for treating disorders associated with IGFR kinases.</p>
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SYNTHESIS OF PYRAZOLES (Fri, 23 Oct 2009)
<p id="p-0001-en" num="0000">The present invention provides compounds and compositions, methods of making them, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.</p>
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AMINO-IMIDAZOLONES FOR THE INHIBITION OF BETA-SECRETASE (Fri, 09 Oct 2009)
<p id="p-0001-en" num="0000">The present invention provides an amino-imidazolone compound of formula I</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="39.20mm" wi="58.08mm" file="us20090253716a1-20091008-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">Also provided are compositions and methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.</p>
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HETEROCYCLYL-3-SULFONYLINDAZOLES AS 5-HYDROXYTRYPTAMINE-6 LIGANDS (Fri, 09 Oct 2009)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I and the use thereof in the therapeutic treatment of disorders related to or affected by the 5-HT6 receptor.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="36.58mm" wi="69.85mm" file="us20090253711a1-20091008-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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Production of polyketides and other natural products (Fri, 09 Oct 2009)
<p id="p-0001-en" num="0000">The present invention relates to production of polyketides and other natural products and to libraries of compounds and individual novel compounds. Therefore in aspect the present invention provides 17-desmethylrapamycin and analogues thereof, methods for their production, including recombinant strains, and isolation and uses of the compounds of the invention. In a further aspect the present invention provides for the use of 17-desmethylrapamycin and analogues thereof in the induction or maintenance of immunosuppression, the stimulation of neuronal regeneration or the treatment of cancer, B-cell malignancies, fungal infections, transplantation rejection, graft vs. host disease, autoimmune disorders, diseases of inflammation vascular disease and fibrotic diseases, and in the regulation of wound healing.</p>
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1-ARYL-OR 1- ALKYLSULFONYLBENZAZOLE DERIVATIVES AS 5-HYDROXYTRYPTAMINE-6 LIGANDS (Fri, 25 Sep 2009)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I and the use thereof for the therapeutic treatment of disorders relating to or affected by the 5-HT6 receptor.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="27.43mm" wi="69.85mm" file="us20090239863a1-20090924-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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ANTIBODIES AGAINST INTERLEUKIN-10 LIKE CYTOKINES AND USES THEREFOR (Fri, 25 Sep 2009)
Specific binding fragments, antibodies, and antigen-binding fragments thereof that bind IL-10-like cytokines, including human interleukin-22 (IL-22) are provided. Methods of making and using such binding fragments, antibodies, and antigen-binding fragments are also provided. Kits containing such binding fragments, antibodies, and antigen-binding fragments are also provided.
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ANTIBODIES AGAINST INTERLEUKIN-10-LIKE CYTOKINES AND USES THEREFOR (Fri, 25 Sep 2009)
Specific binding fragments, antibodies, and antigen-binding fragments thereof that bind IL-10-like cytokines, including human interleukin-22 (IL-22) are provided. Methods of making and using such binding fragments, antibodies, and antigen-binding fragments are also provided. Kits containing such binding fragments, antibodies, and antigen-binding fragments are also provided. </p>
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7H-PYRROLO[2,3-H]QUINAZOLINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESIS (Sat, 12 Sep 2009)
A 7H-pyrrolo[2,3-h]quinazoline compound of the formula (I) wherein Ar, R1, R2, R7, R8, R9, R10, R11, R12, and n are as defined in the specification as P13 kinase inhibitors and mTOR kinase inhibitors.
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Biphenyl Vasopressin Agonists (Fri, 11 Sep 2009)
<p id="p-0001-en" num="0000">A compound of the formulae (I) or (II):</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">wherein: <ul id="ul0001-en" list-style="none"><li>Y is a moiety selected from NR or —(CH<sub>2</sub>)<sub>n</sub>;</li><li>wherein R is hydrogen or (C<sub>1</sub>-C<sub>6</sub>) lower alkyl,</li><li>and n is 1;</li></ul></p> <p id="p-0004-en" num="0000"/> <p id="p-0005-en" num="0000">represents: <ul id="ul0002-en" list-style="none"><li><ul id="ul0003-en" list-style="none"><li>(1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C<sub>1</sub>-C<sub>6</sub>) lower alkyl, halogen, cyano, CF<sub>3</sub>, hydroxy, (C<sub>1</sub>-C<sub>6</sub>) lower alkoxy, (C<sub>1</sub>-C<sub>6</sub>) lower alkoxy carbonyl, carboxy, —CONH<sub>2</sub>, —CONH[(C<sub>1</sub>-C<sub>6</sub>) lower alkyl], —CON[(C<sub>1</sub>-C<sub>6</sub>) lower alkyl]<sub>2</sub>; or</li><li>(2) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C<sub>1</sub>-C<sub>6</sub>) lower alkyl, halogen or (C<sub>1</sub>-C<sub>6</sub>) lower alkoxy;</li></ul></li></ul></p> <p id="p-0006-en" num="0000"/> <p id="p-0007-en" num="0000">represents: <ul id="ul0004-en" list-style="none"><li><ul id="ul0005-en" list-style="none"><li>(1) a phenyl ring optionally substituted with one or two substituents selected, independently, from the group comprising hydrogen, (C<sub>1</sub>-C<sub>6</sub>) lower alkyl, halogen, cyano, CF<sub>3</sub>, hydroxy, (C<sub>1</sub>-C<sub>6</sub>) lower alkoxy, or (C<sub>1</sub>-C<sub>6</sub>) lower alkoxy carbonyl, carboxy, —CONH<sub>2</sub>, —CONH[(C<sub>1</sub>-C<sub>6</sub>) lower alkyl], —CON[(C<sub>1</sub>-C<sub>6</sub>) lower alkyl]<sub>2</sub>; or</li><li>(2) a 5-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C<sub>1</sub>-C<sub>6</sub>) lower alkyl, (C<sub>1</sub>-C<sub>6</sub>) lower alkoxy, or halogen; or</li><li>(3) a 6-membered aromatic (unsaturated) heterocyclic ring having one nitrogen atom, optionally substituted by (C<sub>1</sub>-C<sub>6</sub>) lower alkyl, halogen, or (C<sub>1</sub>-C<sub>6</sub>) lower alkoxy;</li></ul></li></ul></p> <p id="p-0008-en" num="0000"/> <p id="p-0009-en" num="0000">represents a 5-membered aromatic (unsaturated) heterocyclic ring having one sulfur atom, optionally substituted by (C<sub>1</sub>-C<sub>6</sub>) lower alkyl, halogen, or (C<sub>1</sub>-C<sub>6</sub>) lower alkoxy; <ul id="ul0006-en" list-style="none"><li><ul id="ul0007-en" list-style="none"><li>R<sub>1 </sub>is a moiety of the formula</li></ul></li></ul></p> <p id="p-0010-en" num="0000"/> <p id="p-0011-en" num="0000">and R<sub>2</sub>, R<sub>3</sub>, R<sub>7</sub>, R<sub>8 </sub>and R<sub>9 </sub>are, independently, selected from a group consisting of hydrogen, (C<sub>1</sub>-C<sub>3</sub>) lower alkyl, OCH<sub>3</sub>, halogen, CF<sub>3</sub>, —SCH<sub>3</sub>, OCF<sub>3</sub>, SCF<sub>3</sub>, or CN; <br/> or a pharmaceutically acceptable salt, or pro-drug form thereof. </p>
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7H-PYRROLO[2,3-H]QUINAZOLINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESIS (Fri, 11 Sep 2009)
<p id="p-0001-en" num="0000">A 7H-pyrrolo[2,3-h]quinazoline compound of the formula I</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">wherein Ar, R<sup>1</sup>, R<sup>2</sup>, R<sup>7</sup>, R<sup>8</sup>, R<sup>9</sup>, R<sup>10</sup>, R<sup>11</sup>, R<sup>12</sup>, and n are as defined in the specification, and methods for making same.</p>
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Fluoro- and trifluoroalkyl-containing heterocyclic sulfonamide inhibitors of beta amyloid production and derivatives thereof (Fri, 11 Sep 2009)
<p id="p-0001-en" num="0000">Compounds of Formula (I),</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="18.37mm" wi="69.93mm" file="US07858658-20101228-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> are provided where T is CHO, COR<sub>8</sub>, or C(OH)R<sub>1</sub>R<sub>2</sub>; R<sub>1 </sub>and R<sub>2 </sub>are hydrogen, optionally substituted lower alkyl, CF<sub>3</sub>, optionally substituted alkenyl, or optionally substituted alkynyl; R<sub>3 </sub>is hydrogen or optionally substituted lower alkyl; R<sub>4 </sub>is (CF<sub>3</sub>)<sub>n</sub>alkyl, (CF<sub>3</sub>)<sub>n</sub>(substitutedalkyl), (CF<sub>3</sub>)<sub>n</sub>alkylphenyl, (CF<sub>3</sub>)<sub>n</sub>alkyl(substitutedphenyl), or (F)<sub>n</sub>cycloalkyl; n=1-3; R<sub>5 </sub>is hydrogen, halogen, CF<sub>3</sub>, diene fused to Y when Y=C, or substituted diene fused to Y when Y=C; W, Y and Z are C, CR<sub>6 </sub>or N where at least one of W, Y or Z are C; R<sub>6 </sub>is hydrogen, halogen, or optionally substituted lower alkyl; X is O, S, SO<sub>2</sub>, or NR<sub>7</sub>; R<sub>7 </sub>is hydrogen, optionally substituted lower alkyl, optionally substituted benzyl, or optionally substituted phenyl; and R<sub>8 </sub>is lower alkyl, CF<sub>3</sub>, or optionally substituted phenyl. Methods of preparing and using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are also described. </p>
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TRIFLUOROMETHYL-CONTAINING PHENYLSULFONAMIDE BETA AMYLOID INHIBITORS (Fri, 04 Sep 2009)
<p id="p-0001-en" num="0000">A compound of Formula (I), or pharmaceutically acceptable salts and/or hydrates or prodrugs thereof, wherein Formula (I) has the structure:</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">is provided, wherein R<sub>1</sub>-R<sub>7 </sub>are defined herein. These compounds are useful in medicaments for treating a disease selected from the group consisting of Alzheimer's disease, amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, mild cognitive impairment (MCI) and Down's syndrome, in a subject.</p>
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FUSED TRICYCLIC PYRAZOLO[1, 5-A]PYRIMIDINES, METHODS FOR PREPARATION AND USES THEREOF (Fri, 04 Sep 2009)
Fused, tricyclic pyrazolo{1,5-a]pyrimidine compounds of formula A or of formula B: and pharmaceutically acceptable salts thereof are described, which selectively inhibit Raf kinase activity and are useful for treating disorders mediated by certain Raf kinases.
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BRIDGED, BICYCLIC HETEROCYCLIC OR SPIRO BICYCLIC HETEROCYCLIC DERIVATIVES OF PYRAZOLO[1,5-A]PYRIMIDINES, METHODS FOR PREPARATION AND USES THEREOF (Fri, 04 Sep 2009)
Compounds of formula A and pharmaceutically acceptable salts thereof are described, which selectively inhibit Raf kinase activity and are useful for treating disorders mediated by Raf kinases.
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BRIDGED, BICYCLIC HETEROCYCLIC OR SPIRO BICYCLIC HETEROCYCLIC DERIVATIVES OF PYRAZOLO[1,5-A]PYRIMIDINES, METHODS FOR PREPARATION AND USES THEREOF (Fri, 04 Sep 2009)
Compounds of formula A and pharmaceutically acceptable salts thereof are described, which selectively inhibit Raf kinase activity and are useful for treating disorders mediated by Raf kinases. </p>
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SELECTIVE ACYLATION OF 4-SUBSTITUTED-1,3-PHENYLENEDIAMINE (Fri, 28 Aug 2009)
<p id="p-0001-en" num="0000">This invention is directed to a method of selectively acylating a compound of formula (II): (II), wherein: R<sup>1 </sup>is NO<sub>2</sub>, —N<sup>+</sup>R<sup>3</sup><sub>3</sub>, trihalomethyl, —CN, —SO<sub>3</sub>H, —CO<sub>2</sub>H, —CO<sub>2 </sub>R<sup>3</sup>, —CHO and —COR<sub>3</sub>, wherein R<sup>3 </sup>is C<sub>1</sub>-C<sub>6 </sub>alkyl, C<sub>1</sub>-C<sub>6 </sub>haloalkyl, C<sub>3</sub>-C<sub>12 </sub>cycloalkyl, C<sub>6</sub>-C<sub>12 </sub>aryl, C<sub>2</sub>-C<sub>9 </sub>heteroaryl, or C<sub>1</sub>-C<sub>9 </sub>heterocycloalkyl; comprising the step of reacting the compound of formula (II) with an acylating reagent to form a compound of formula (I): (I), wherein R<sup>2 </sup>is selected from C<sub>1</sub>-C<sub>12 </sub>alkyl, C<sub>1</sub>-C<sub>12 </sub>haloalkyl, C<sub>2</sub>-C<sub>7 </sub>alkenyl, C<sub>2</sub>-C<sub>7 </sub>alkynyl, C<sub>3</sub>-C<sub>12 </sub>cycloalkyl, C<sub>6</sub>-C<sub>12 </sub>aryl, C<sub>1</sub>-C<sub>9 </sub>heterocycloalkyl, C<sub>2</sub>-C<sub>9 </sub>heteroaryl, C<sub>1</sub>-C<sub>12 </sub>alkoxy, C<sub>1</sub>-C<sub>12 </sub>haloalkoxy, C<sub>3</sub>-C<sub>12 </sub>cycloalkoxy, C<sub>1</sub>-C<sub>9 </sub>heterocycloalkoxy, C<sub>6</sub>-C<sub>12 </sub>aryloxy, and C<sub>2</sub>-C<sub>9 </sub>heteroaryloxy; or salts thereof.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="69.43mm" wi="49.11mm" file="us20090216046a1-20090827-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHODS FOR USING RAPAMYCIN ANALOGUES IN THE TREATMENT OF NEUROLOGICAL DISORDERS (Fri, 28 Aug 2009)
The present invention provides methods for treatment of neurological disorders or complications due to stroke or head injury; benign or malignant neoplastic disease, carcinomas and adenocarcinomas; proliferative disorders; and inflammatory disorders, comprising administering a compound as described herein to a subject in need thereof, and a pharmaceutically acceptable carrier, within a therapeutic window that is from about 4 hours to 24 hours, or longer, for example at least 4, 6, 9, 12, 15, 18, 21 or 24 hours, or longer, after the onset of the neurological, proliferative, or inflammatory disorder or a symptom thereof. In some embodiments, the compounds of the following structure, wherein R1, R2, R4, R4', R6, R7, and R15 are as defined herein:
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Methods for Using Rapamycin Analogues in the Treatment of Neurological Disorders (Fri, 21 Aug 2009)
<p id="p-0001-en" num="0000">The present invention provides methods for treatment of neurological disorders or complications due to stroke or head injury; benign or malignant neoplastic disease, carcinomas and adenocarcinomas; proliferative disorders; and inflammatory disorders, comprising administering a compound as described herein to a subject in need thereof, and a pharmaceutically acceptable carrier, within a therapeutic window that is from about 4 hours to 24 hours, or longer, for example at least 4, 6, 9, 12, 15, 18, 21 or 24 hours, or longer, after the onset of the neurological, proliferative, or inflammatory disorder or a symptom thereof. In some embodiments, the compounds of the following structure, wherein R<sub>1</sub>, R<sub>2</sub>, R<sub>4</sub>, R<sub>4′</sub>, R<sub>6</sub>, R<sub>7</sub>, and R<sub>15 </sub>are as defined herein:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="62.65mm" wi="65.28mm" file="us20090209527a1-20090820-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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AMORPHOUS POLYMORPH OF BAZEDOXIFENE ACETATE (Fri, 21 Aug 2009)
The invention provides a novel polymorphic form C of bazedoxifene acetate, methods of preparing the polymorphic form, and compositions and methods of treatment using the polymorphic form.
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Rapamycin Analogues and the Uses Thereof in the Treatment of Neurological Disorders (Fri, 14 Aug 2009)
<p id="p-0001-en" num="0000">Method of treatment of neurological disorders or complications due to stroke or head injury through the administration of a pharmaceutical composition including a pharmaceutically acceptable excipient or carrier and a compound of formula I are provided:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="62.65mm" wi="70.87mm" file="us20090203682a1-20090813-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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SUBSTITUTED BENZO[d][1,3]OXAZIN-2(4H)-ONES AND RELATED DERIVATIVES AND THEIR USES FOR MODULATING THE PROGESTERONE RECEPTOR (Fri, 07 Aug 2009)
<p id="p-0001-en" num="0000">Compounds of formula (I), or pharmaceutically acceptable salts thereof, are provided, wherein R<sub>1</sub>-R<sub>6 </sub>and X are defined herein. Also provided are methods of preparing the compounds of formula (I), pharmaceutical compositions and kits containing a compound of formula (I), as are methods of treating endometriosis, hormone-dependent carcinomas, leiomyoma, fibroids, dysfunctional bleeding, polycystic ovary syndrome, and menopause related symptoms; methods of contraception; methods of providing hormone replacement therapy; methods of stimulating food intake; methods of synchronizing estrus; and methods of treating symptoms of premenstrual syndrome and premenstrual dysphoric disorder by administering to a mammal in need thereof a pharmaceutically effective amount of a compound of formula (I).</p> <p id="p-0002-en" num="0000"/>
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1H-PYRAZOLO[3,4-D]PYRIMIDINE, PURINE, 7H-PURIN-8(9H)-ONE, 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE, AND THIENO[3,2-D]PYRIMIDINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 07 Aug 2009)
The invention relates to 1H-pyrazolo[3,4-d]pyrimidine, purine, 7H-purin-8(9H)-one, 3H-[1,2,3]triazolo[4,5-d]pyrimidine, and thieno[3,2-d]pyrimidine compounds, compositions comprising the compounds, and methods for making and using the compounds.
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[A]-FUSED INDOLE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 07 Aug 2009)
The invention relates to [a]-fused indole compounds of the Formula II, or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein. The invention also relates to compositions comprising the compounds of Formula II, and methods for making and using the compounds.
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[a]-FUSED INDOLE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 31 Jul 2009)
<p id="p-0001-en" num="0000">The invention relates to [a]-fused indole compounds of the Formula II,</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein. The invention also relates to compositions comprising the compounds of Formula II, and methods for making and using the compounds.</p>
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Pyrimidinyl amide compounds which inhibit leukocyte adhesion mediated by VLA-4 (Fri, 31 Jul 2009)
<p id="p-0001-en" num="0000">Disclosed are compounds which bind VLA-4. Certain of these compounds also inhibit leukocyte adhesion and, in particular, leukocyte adhesion mediated by VLA-4. Such compounds are useful in the treatment of inflammatory diseases in a human or animal subject such as asthma, Alzheimer's disease, atherosclerosis, AIDS dementia, diabetes, inflammatory bowel disease, rheumatoid arthritis, tissue transplantation, tumor metastasis and myocardial ischemia. The compounds can also be administered for the treatment of inflammatory brain diseases such as multiple sclerosis.</p>
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1H-PYRAZOLO[3,4-D]PYRIMIDINE, PURINE, 7H-PURIN-8(9H)-ONE, 3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE, AND THIENO[3,2-D]PYRIMIDINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 31 Jul 2009)
<p id="p-0001-en" num="0000">The invention relates to 1H-pyrazolo[3,4-d]pyrimidine, purine, 7H-purin-8(9H)-one, 3H-[1,2,3]triazolo[4,5-d]pyrimidine, and thieno[3,2-d]pyrimidine compounds, compositions comprising the compounds, and methods for making and using the compounds.</p>
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SYNTHESIS OF PYRAZOLES (Fri, 24 Jul 2009)
The present invention provides methods of making HCl salts, and methods of using them to modulate alpha7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory system.
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COMPOUND FORMS AND USES THEREOF (Fri, 24 Jul 2009)
The present invention provides, among other things, forms of a compound of formula 1. In some embodiments, the present invention provides salt forms and/or crystal forms. In some embodiments, the present invention provides solid forms. The present invention also provides methods of making and using provided forms.
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COMPOUNDS USEFUL AS ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS (Fri, 24 Jul 2009)
The present invention provides compounds and compositions, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory systems.
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3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 24 Jul 2009)
The invention relates to 3H-[1,2,3]triazolo[4,5-d]pyrimidine compounds of the Formula 1 or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
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3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 24 Jul 2009)
The invention relates to 3H-[1,2,3]triazolo[4,5-d]pyrimidine compounds of the Formula 1 or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds. </p>
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COMPOSITIONS CONTAINING O-SULFATE AND O-PHOSPHATE CONTAINING ARYL SULFONAMIDE DERIVATIVES USEFUL AS beta-AMYLOID INHIBITORS (Fri, 17 Jul 2009)
<p id="p-0001-en" num="0000">A synthetic compound characterized by having the structure of formula I or II or a pharmaceutically acceptable salt and/or hydrate thereof is provided. Formula I and formula II are defined as follows.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="62.40mm" wi="57.15mm" file="us20090181932a1-20090716-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">wherein R<sub>1 </sub>is substituted aryl or substituted heteroaryl; R<sub>2 </sub>and R<sub>3 </sub>are independently selected from the group consisting of CF<sub>3</sub>, substituted phenyl, C<sub>1</sub>-C<sub>4 </sub>alkyl, substituted C<sub>1</sub>-C<sub>4 </sub>alkyl, (CF<sub>3</sub>)<sub>n</sub>C<sub>1</sub>-C<sub>4</sub>alkyl, (CF<sub>3</sub>)<sub>n</sub>(substituted C<sub>1</sub>-C<sub>4 </sub>alkyl), provided that when R<sub>2 </sub>or R<sub>3 </sub>is CF<sub>3</sub>, the other is not an unsubstituted alkyl; R<sub>4 </sub>and R<sub>4′ </sub>are independently selected from the group consisting of M, C<sub>1</sub>-C<sub>4 </sub>alkyl, phenyl, and benzyl, wherein M is a metal ion is selected from the group consisting of sodium, lithium, calcium, magnesium and potassium, or R<sub>4 </sub>and R<sub>4′ </sub>are taken together to form a cyclic structure. Methods of making such compounds and uses thereof are also provided.</p>
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3H-[1,2,3]TRIAZOLO[4,5-D]PYRIMIDINE COMPOUNDS, THEIR USE AS mTOR KINASE AND PI3 KINASE INHIBITORS, AND THEIR SYNTHESES (Fri, 17 Jul 2009)
<p id="p-0001-en" num="0000">The invention relates to 3H-[1,2,3]triazolo[4,5-d]pyrimidine compounds of the Formula 1:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="40.98mm" wi="51.56mm" file="us20090181963a1-20090716-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.</p>
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COMPOUND FORMS AND USES THEREOF (Fri, 17 Jul 2009)
<p id="p-0001-en" num="0000">The present invention provides, among other things, forms of a compound of formula 1. In some embodiments, the present invention provides salt forms and/or crystal forms. In some embodiments, the present invention provides solid forms. The present invention also provides methods of making and using provided forms.</p>
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COMPOUNDS USEFUL AS ALPHA7 NICOTINIC ACETYLCHOLINE RECEPTOR AGONISTS (Fri, 17 Jul 2009)
<p id="p-0001-en" num="0000">The present invention provides compounds and compositions, and methods of using them to modulate α7 nicotinic acetylcholine receptors and/or to treat any of a variety of disorders, diseases, and conditions. Provided compounds can affect, among other things, neurological, psychiatric and/or inflammatory systems.</p>
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COMPOSITIONS CONTAINING O-SULFATE AND O-PHOSPHATE CONTAINING ARYL SULFONAMIDE DERIVATIVES USEFUL AS BETA-AMYLOID INHIBITORS (Fri, 17 Jul 2009)
A synthetic compound characterized by having the structure of formula I or II or a pharmaceutically acceptable salt and/or hydrate thereof is provided. Formula I and formula II are defined as follows. wherein R1 is substituted aryl or substituted heteroaryl; R2 and R3 are independently selected from the group consisting of CF3, substituted phenyl, C1-C4 alkyl, substituted C1-C4 alkyl, (CF3)nC1-C4 alkyl, (CF3)n(substituted C1-C4 alkyl), provided that when R2 or R3 is CF3, the other is not an unsubstituted alkyl; R4 and R4,are independently selected from the group consisting of M, C1-C4 alkyl, phenyl, and benzyl, wherein M is a metal ion is selected from the group consisting of sodium, lithium, calcium, magnesium and potassium, or R4 and R4, are taken together to form a cyclic structure. Methods of making such compounds and uses thereof are also provided.
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2-PHENYL-1-[4-(2-AMINOETHOXY)-BENZYL]-INDOLES AS ESTROGENIC AGENTS (Fri, 10 Jul 2009)
<p id="p-0001-en" num="0000">The present invention relates to new 2-Phenyl-<b>1</b>-[4-(2-Aminoethoxy)-Benzyl]-Indole compounds having the general structures below:</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">which are useful in treating osteoporosis, acne, dysfunctional uterine bleeding, endometrial polyps, benign breast disease, adenomyosis, infertility, endometriosis, endometrial cancer, polycystic ovary syndrome, cardiovascular disease, Alzheimer's disease, cognitive decline, central nervous system disorders, central nervous system cancers, leukemia, endometrial ablations, chronic renal disease, chronic hepatic disease, coagulation diseases and disorders, hypocalcemia, hypercalcemia, Paget's disease, osteomalacia, osteohalisteresis, and multiple myeloma.</p>
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Maleate salts of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide and crystalline forms thereof (Fri, 10 Jul 2009)
<p id="p-0001" num="0000">The present invention relates to maleate salt forms of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide, methods of preparing crystalline maleate salt forms, the associated compounds, and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family.</p>
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IMIDAZO [1,2-A] PYRIDINE COMPOUNDS (Fri, 10 Jul 2009)
This invention relates generally to imidazo [1,2-a] pyridine-based modulators of Liver X receptors (LXRs) having formula (I) and related methods: wherein R2 is C6-C10 aryl or heteroaryl including 5-10 atoms, each of which is : (i) substituted with 1 R7, and (ii) optionally substituted with form 1-5 Re; and R1, R3, R4, R5, R6, R7 and Re are defined herein.
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IMIDAZO [1,2-A] PYRIDINE COMPOUNDS (Fri, 10 Jul 2009)
Ibis invention relates generally to imidazo [1,2-a] pyridine-based modulators of Liver X receptors (LXRs) having formula (I) and related methods: wherein R2 is C6-C10 aryl or heteroaryl including 5-10 atoms, each of which is : (i) substituted with 1 R7, and (ii) optionally substituted with form 1-5 R e; and R1, R3, R4, R5, R6, R7 and R e are defined herein. </p>
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4-IMIDAZOLIDINONES AS KV1.5 POTASSIUM CHANNEL INHIBITORS (Fri, 26 Jun 2009)
The present teachings relate to 4-imidazolidinones of Formula (I) Insert formula here as it appears in written form in the specification (I) which are useful as Kv1.5 potassium channel inhibitors providing atrial-selective antiarrhythmic activity. The present teachings further relate to compositions and methods for treating atrial-selective antiarrhythmia.
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4-IMIDAZOLIDINONES AS KV1.5 POTASSIUM CHANNEL INHIBITORS (Fri, 26 Jun 2009)
The present teachings relate to 4-imidazolidinones of Formula (I) Insert formula here as it appears in written form in the specification (I) which are useful as Kv1.5 potassium channel inhibitors providing atrial-selective antiarrhythmic activity. The present teachings further relate to compositions and methods for treating atrial-selective antiarrhythmia. </p>
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HIGH RESOLUTION STRUCTURES OF ACIDIC MAMMALIAN CHITINASES AND USES THEREOF (Fri, 19 Jun 2009)
High resolution structures of acidic mammalian chitinase (AMCase) are disclosed. The structures disclosed herein enable selection of, and structure-based rational drug design of, agents that modulate, e.g., antagonize, AMCase activity. Thus, crystal compositions, methods of selecting and/or designing agents, e.g., antagonists, of AMCase, and computer and software programs are disclosed.
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5-ALKYL/ALKENYL-3-CYANOPYRIDINES AS KINASE INHIBITORS (Fri, 19 Jun 2009)
Described herein are compounds of formula I: wherein G is and pharmaceutically acceptable salts thereof, wherein J, X, R1, R2, R11, R12' and p are as defined herein. Also provided herein are methods of making the compounds of formula I, and methods of using these compounds for inhibiting or treating a pathological condition or disorder linked to or mediated by a protein kinase in a mammal.
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5-ALKYL/ALKENYL-3-CYANOPYRIDINES AS KINASE INHIBITORS (Fri, 19 Jun 2009)
Described herein are compounds of formula I: wherein G is and pharmaceutically acceptable salts thereof, wherein J, X, R1, R2, R11, R12' and p are as defined herein. Also provided herein are methods of making the compounds of formula I, and methods of using these compounds for inhibiting or treating a pathological condition or disorder linked to or mediated by a protein kinase in a mammal. </p>
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PYRROLO[3,2-d]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND mTOR KINASE INHIBITORS (Fri, 12 Jun 2009)
<p id="p-0001-en" num="0000">A pyrrolo[3,2-d]pyrimidine compound, such as a compound of the formula (I):</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.</p>
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INTERLEUKIN-17F ANTIBODIES AND OTHER IL-17F SIGNALING ANTAGONISTS AND USES THEREFOR (Fri, 05 Jun 2009)
<p id="p-0001-en" num="0000">The present invention provides isolated and purified polynucleotides and polypeptides related to the IL-17F signaling pathway. The invention also provides antibodies to IL-17F homodimers and IL-17A/IL-17F heterodimers, and methods of isolating and purifying members of the IL-17 family, including IL-17A/IL-17F heterodimers, from a natural source. The present invention also is directed to novel methods for diagnosing, prognosing, monitoring the progress of, and treating and/or preventing disorders related to IL-17F signaling, i.e., IL-17F-associated disorders, including, but not limited to, inflammatory disorders, such as autoimmune diseases (e.g., arthritis (including rheumatoid arthritis), psoriasis, systemic lupus erythematosus, and multiple sclerosis), respiratory diseases (e.g., COPD, cystic fibrosis, asthma, allergy), transplant rejection (including solid organ transplant rejection), and inflammatory bowel diseases or disorders (IBDs, e.g., ulcerative colitis, Crohn's disease). The present invention is further directed to novel therapeutics and therapeutic targets, and to methods of screening and assessing test compounds for the intervention (treatment) and prevention of disorders related to IL-17F signaling.</p>
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Thioamide derivatives as progesterone receptor modulators (Fri, 05 Jun 2009)
<p id="p-0001-en" num="0000">Thioamide compounds, and specifically, thioamide pyrrole compounds, and preparation thereof are provided. These thioamide compounds can be used as progesterone receptor modulators, in contraception, and in the treatment of progesterone-related maladies.</p>
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Pyrido[3,2-E]Pyrazines, Process For Preparing The Same, And Their Use As Inhibitors Of Phosphodiesterase 10 (Fri, 05 Jun 2009)
<p id="p-0001-en" num="0000">The invention relates to pyrido[3,2-e]pyrazines, to processes for preparing them, to pharmaceutical compositions which comprise these compounds and to the pharmaceutical use of these compounds, which are inhibitors of phosphodiesterase 10, as active compounds for treating central nervous system disorders, obesity, and metabolic disorders.</p>
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Substituted imidazo[1,5-a]quinoxalines useful as inhibitors of phosphodiesterase 10 for the treatment of neurological and other disorders (Fri, 05 Jun 2009)
<p id="p-0001" num="0000">The invention relates to imidazo[1,5-a]quinoxaline derivatives having Formula IIa:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="25.99mm" wi="58.17mm" file="US07875618-20110125-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> to processes for preparing them, to pharmaceutical preparations which comprise these compounds and to the pharmaceutical use of these compounds, which are inhibitors of phosphodiesterase 10 (PDE10), as active compounds for treating central nervous system diseases of mammals, including humans. </p>
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Purification of progesterone receptor modulators (Fri, 05 Jun 2009)
<p id="p-0001" num="0000">Methods for purifying a compound of formula I are provided, wherein A, B, X, Q, and R<sup>1 </sup>are defined herein.</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="22.52mm" wi="51.31mm" file="US08309594-20121113-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003" num="0000">The methods include mixing the compound of formula I and a solvent; adding a base to the solvent; and precipitating purified compound of formula I.</p>
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PYRIDO[3,2-E]PYRAZINES, PROCESS FOR PREPARING THE SAME, AND THEIR USE AS INHIBITORS OF PHOSPHODIESTERASE 10 (Fri, 05 Jun 2009)
The invention relates to pyrido[3,2-e]pyrazines, to processes for preparing them, to pharmaceutical compositions which comprise these compounds and to the pharmaceutical use of these compounds, which are inhibitors of phosphodiesterase 10, as active compounds for treating central nervous system disorders, obesity, and metabolic disorders.
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PYRROLO[3,2-D]PYRIMIDINE COMPOUNDS AND THEIR USE AS PI3 KINASE AND MTOR KINASE INHIBITORS (Fri, 05 Jun 2009)
A pyrrolo[3,2-d]pyrimidine compound, such as a compound of the formula (I); or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds, useful for treating PI3K-related diseases.
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ARYL AND HETEROARYL FUSED IMIDAZO[1,5-A]PYRAZINES AS INHIBITORS OF PHOSPHODIESTERASE 10 (Fri, 05 Jun 2009)
The invention relates to imidazo[1,5-a]pyrazine derivatives, to processes for preparing them, to pharmaceutical preparations which comprise these compounds and to the pharmaceutical use of these compounds, which are inhibitors of phosphodiesterase 10 (PDE10), as active compounds for treating central nervous system diseases of mammals, including humans.
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ARYL AND HETEROARYL FUSED IMIDAZO[1,5-A]PYRAZINES AS INHIBITORS OF PHOSPHODIESTERASE 10 (Fri, 05 Jun 2009)
The invention relates to imidazo[1,5-a]pyrazine derivatives, to processes for preparing them, to pharmaceutical preparations which comprise these compounds and to the pharmaceutical use of these compounds, which are inhibitors of phospho-diesterase (PDE10), as active compounds for treating central nervous system diseases of mammals, including humans. </p>
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HBM variants that modulate bone mass and lipid levels (Fri, 29 May 2009)
<p id="p-0001-en" num="0000">The present invention relates to methods and materials used to express an HBM-like polypeptide derived from HBM, LRP5 or LRP6 in animal cells and transgenic animals. The present invention also relates to transgenic animals expressing the HBM-like polypeptides. The invention provides nucleic acids, including coding sequences, oligonucleotide primers and probes, proteins, cloning vectors, expression vectors, transformed hosts, methods of developing pharmaceutical compositions, methods of identifying molecules involved in bone development, and methods of diagnosing and treating diseases involved in bone development and lipid modulation. In preferred embodiments, the present invention is directed to methods for treating, diagnosing and preventing osteoporosis.</p>
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BAZEDOXIFENE ASCORBATE (Fri, 29 May 2009)
<p id="p-0001-en" num="0000">The present invention is directed to bazedoxifene ascorbate, compositions containing the same, dispersions thereof, preparations thereof, and uses thereof.</p>
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THIENOPYRIMIDINES, THIENOPYRIDINES, AND PYRROLOPYRIMIDINES AS B-RAF INHIBITORS (Fri, 08 May 2009)
<p id="p-0001-en" num="0000">The present invention relates to compounds of formula la:</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">and pharmaceutically acceptable salts thereof. The thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, thieno[3,2-b]pyridine, thieno[2,3-b]pyridine, and pyrrolo[2,3-d]pyrimidine compounds selectively inhibit B-Raf kinase activity and are useful for treating disorders mediated by B-Raf kinase, and for the treatment of cancer.</p>
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HETEROARYL ETHERS AND PROCESSES FOR THEIR PREPARATION (Fri, 08 May 2009)
The present invention relates to processes for the preparation of of heteroaryl ethers. In some embodiments, the processes relate to cross coupling reactions between triazol-1-yloxy and triazol-1-yl heterocycles with aryl boronic acids. In a further aspect, this invention also relates to compounds that are useful for the treatment of oncological diseases or disorders, and for the treatment of inflammation.
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THIENOPYRIMIDINES, THIENOPYRIDINES, AND PYRROLOPYRIMIDINES AS B-RAF INHIBITORS (Fri, 08 May 2009)
The present invention relates to compounds of formula (Ia): and pharmaceutically acceptable salts thereof. The thieno[3,2-d]pyrimidine, thieno[2,3-d]pyrimidine, thieno[3,2-b]pyridine, thieno[2,3-b]pyridine, and pyrrolo[2,3-d]pyrimidine compounds selectively inhibit B-Raf kinase activity and are useful for treating disorders mediated by B-Raf kinase, and for the treatment of cancer.
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Indole acetic acids exhibiting CRTH2 receptor antagonism and uses thereof (Fri, 01 May 2009)
<p id="p-0001-en" num="0000">The invention relates to indole acetic acid compounds which function as antagonists of the CRTH2 receptor. The invention also relates to the use of these compounds to inhibit the binding of prostaglandin D<sub>2 </sub>and its metabolites or certain thromboxane metabolites to the CRTH2 receptor and to treat disorders responsive to such inhibition.</p>
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CYCLOCARBAMATE DERIVATIVES AS PROGESTERONE RECEPTOR MODULATORS (Fri, 01 May 2009)
<p id="p-0001-en" num="0000">This invention provides compounds of Formula (I):</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">wherein R<sup>1 </sup>and R<sup>2 </sup>are independent substituents or are fused to form spirocyclic rings; R<sup>3</sup>, R<sup>C</sup>, and R<sup>4 </sup>are as defined herein; and R<sup>5 </sup>is a substituted benzene ring or a substituted five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms including O, S, SO, SO<sub>2 </sub>or NR<sup>6</sup>; or pharmaceutically acceptable salt thereof, as well as pharmaceutical compositions and methods using the compounds as antagonists of the progesterone receptor.</p>
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ERBB2 BINDING PROTEINS AND USE THEREOF (Fri, 01 May 2009)
The present application provides novel binding proteins, including human binding proteins that specifically bind to the human ErbB2.
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SULFONYL-3-HETEROCYCLYLINDAZOLE DERIVATIVES AS 5-HYDROXYTRYPTAMINE-6 LIGANDS (Fri, 24 Apr 2009)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I and the use thereof for the treatment of a central nervous system disorder related to or affected by the 5-HT6 receptor.</p> <p id="p-0002-en" num="0000"/>
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Biosynthetic gene cluster for the production of a complex polyketide (Fri, 24 Apr 2009)
<p id="p-0001" num="0000">A polyketide synthase complex composed of polyketide synthase with 15 total modules, a non-ribosomal peptide synthetase with 1 module, and a cytochrome P450 hydroxylase is described. Also provided are novel <i>Streptomyces </i>species and methods of modified <i>Streptomyces </i>species. Further described are novel compounds, 36-ketomeridamycin, C9-deoxomeridamycin, and C9-deoxoprolylmeridamcyin and uses thereof.</p>
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MALEATE SALTS OF (E)-N-{4-[3-CHLORO-4-(2-PYRIDINYLMETHOXY)ANILINO]-3-CYANO-7-ETHOXY-6-QUINOLINYL}-4-(DIMETHYLAMINO)-2-BUTENAMIDE AND CRYSTALLINE FORMS THEREOF (Fri, 24 Apr 2009)
The present invention relates to maleate salt forms of (E)-N-{4-[3-chloro-4-(2-pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}-4-(dimethylamino)-2-butenamide, (NERATINIB) methods of preparing crystalline maleate salt forms, the associated compounds, such as its degradation and impurities and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family.
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THIENOPYRIMIDINE AND PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS (Fri, 24 Apr 2009)
The invention relates to thienopyrimidine and pyrazolopyrimidine compounds of the Formulas (Ia) and (IIa), or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein compositions comprising the compounds, and methods for making and using the compounds.
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THIENOPYRIMIDINE AND PYRAZOLOPYRIMIDINE COMPOUNDS AND THEIR USE AS MTOR KINASE AND PI3 KINASE INHIBITORS (Fri, 24 Apr 2009)
The invention relates to thienopyrimidine and pyrazolopyrimidine compounds of the Formulas (Ia) and (IIa), or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein compositions comprising the compounds, and methods for making and using the compounds. </p>
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MALEATE SALTS OF (E)-N-{4-[3-CHLORO-4-(2-PYRIDINYLMETHOXY)ANILINO]-3-CYANO-7-ETHOXY-6-QUINOLINYL}-4-(DIMETHYLAMINO)-2-BUTENAMIDE AND CRYSTALLINE FORMS THEREOF (Fri, 24 Apr 2009)
The present invention relates to maleate salt forms of (E)-N-{4-[3-chloro-4-(3- pyridinylmethoxy)anilino]-3-cyano-7-ethoxy-6-quinolinyl}4-(dimethylamino)-2- butenamide, (NERATINIB) methods of preparing crystalline maleate salt forms, the associated compounds, such as its degradation and impurities and pharmaceutical compositions containing the same. The maleate salts are useful in treating cancers, particularly those affected by kinases of the epidermal growth factor receptor family. </p>
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COLOR MEASUREMENTS OF RECONSTITUTED TIGECYCLINE AND DEGRADANT THEREOF (Fri, 17 Apr 2009)
<p id="p-0001-en" num="0000">The present invention relates to a color method and multivariate model whose color measurements of reconstituted tigecycline for injection is predictive of appearance and oxidative degradation wherein said method is a means of detecting the presence of a degradant which forms when tigecycline is contacted with oxygen.</p>
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Thienopyrimidine and pyrazolopyrimidine compounds and their use as mTOR kinase and PI3 kinase inhibitors (Fri, 17 Apr 2009)
<p id="p-0001" num="0000">The invention relates to thienopyrimidine and pyrazolopyrimidine compounds of the Formulas (Ia) and (IIa),</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="61.81mm" wi="69.85mm" file="US08129371-20120306-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> or a pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein compositions comprising the compounds, and methods for making and using the compounds. </p>
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METHOD OF IDENTIFYING COMPOUNDS THAT MODULATE CASPASE 9 ACTIVITY VIA USE OF A KOSMOTROPIC SALT (Fri, 17 Apr 2009)
<p id="p-0001-en" num="0000">The present invention discloses methods for activating Caspase 9 in such a way that it can be used in assays to discover modulators of Caspase 9.</p>
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Phenylaminopropanol Derivatives and Methods of Their Use (Fri, 17 Apr 2009)
<p id="p-0001-en" num="0000">The present invention is directed to phenylaminopropanol derivatives of formula I:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="19.47mm" wi="64.35mm" file="us20090099164a1-20090416-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.</p>
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PREPARATION OF 7-ALKENYL-3 QUINOLINECARBONITRILES VIA A PALLADIUM MEDIATED COUPLING REACTION (Fri, 17 Apr 2009)
<p id="p-0001-en" num="0000">The present invention is directed to a process for preparing compounds of formula (I): wherein A, R<sup>1</sup>-R<sup>3</sup>, X, s, t, u, m and Z are defined herein, comprising the step of reacting a reagent of formula (II): in the presence of Pd(O) metal with a compound of formula (III): or salts thereof. Another aspect of this invention is a method of preparing compounds of formula (VI).</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="107.27mm" wi="63.16mm" file="us20090099356a1-20090416-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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6-CARBOXY-NORMORPHINAN DERIVATIVES, SYNTHESIS AND USES THEREOF (Thu, 16 Apr 2009)
The present invention relates to compounds of formula I, synthesis thereof, and methods of using the same, as antagonists of opioid receptors.
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Phenylaminopropanol Derivatives and Methods of Their Use (Fri, 10 Apr 2009)
<p id="p-0001-en" num="0000">The present invention is directed to phenylaminopropanol derivatives of formula I:</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">or a pharmaceutically acceptable salt thereof, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions ameliorated by monoamine reuptake including, inter alia, vasomotor symptoms (VMS), sexual dysfunction, gastrointestinal and genitourinary disorders, chronic fatigue syndrome, fibromylagia syndrome, nervous system disorders, and combinations thereof, particularly those conditions selected from the group consisting of major depressive disorder, vasomotor symptoms, stress and urge urinary incontinence, fibromyalgia, pain, diabetic neuropathy, and combinations thereof.</p>
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Amino-5,5-diphenylimidazolone derivatives for the inhibition of β-secretase (Fri, 10 Apr 2009)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I and the use thereof for the therapeutic treatment, prevention or amelioration of a disease or disorder characterized by elevated β-amyloid deposits or β-amyloid levels in a patient.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="37.51mm" wi="69.85mm" file="US07700602-20100420-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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Humanized antibodies that recognize beta amyloid peptide (Thu, 09 Apr 2009)
The invention provides improved agents and methods for the treatment of diseases associated with amyloid deposits of A² in the brain of a patient. Preferred agents include humanized antibodies.
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Dihydrobenzofuranyl Alkanamine Derivatives and Methods for Using Same (Fri, 27 Mar 2009)
<p id="p-0001-en" num="0000">Compounds of Formula 1 or pharmaceutically acceptable salts thereof are provided:</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">which are agonists or partial agonists of the 2C subtype of brain serotonin receptors. The compounds, and compositions containing the compounds, can be used to treat a variety of central nervous system disorders such as schizophrenia.</p>
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METHODS FOR PREPARING SULFONAMIDE COMPOUNDS (Fri, 27 Mar 2009)
<p id="p-0001-en" num="0000">Methods for preparing substituted phenylsulfonamide compounds of the following structure are provided:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="27.01mm" wi="48.85mm" file="us20090082591a1-20090326-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">or a pharmaceutically acceptable salt thereof, wherein, R<sub>1</sub>-R<sub>7 </sub>are defined herein. Also provided are methods for preparing compounds of the following structure:</p> <p id="p-0004-en" num="0000"> <chemistry id="chem-us-00002-en" num="00002"> <img id="emi-c00002" he="44.03mm" wi="40.13mm" file="us20090082591a1-20090326-c00002.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0005-en" num="0000">wherein, R<sub>9</sub>, m, n, p, r, and s are defined herein.</p>
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Methods and Compositions for Selectin Inhibition (Fri, 20 Mar 2009)
<p id="p-0001-en" num="0000">The present invention relates to the field of anti-inflammatory substances, and more particularly to novel compounds that act as antagonists of the mammalian adhesion proteins known as selecting. In some embodiments, methods for treating selectin mediated disorders are provided which include administration of compound of Formula I:</p> <p id="p-0002-en" num="0000"> <ul id="ul0001-en" list-style="none"> <li> <ul id="ul0002-en" list-style="none"> <li>wherein the constituent variables are defined herein.</li> </ul> </li> </ul> </p>
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AZACYCLYLISOQUINOLINONE AND ISOINDOLINONE DERIVATIVES AS HISTAMINE-3 ANTAGONISTS (Fri, 20 Mar 2009)
The present invention provides a compound of formula (I) and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.
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ISOQUINOLINYL AND ISOINDOLINYL DERIVATIVES AS HISTAMINE-3 ANTAGONISTS (Fri, 20 Mar 2009)
The present invention provides a compound of formula (I) and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.
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ISOQUINOLINYL AND ISOINDOLINYL DERIVATIVES AS HISTAMINE-3 ANTAGONISTS (Fri, 20 Mar 2009)
The present invention provides a compound of formula (I) and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor. </p>
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AZACYCLYLISOQUINOLINONE AND ISOINDOLINONE DERIVATIVES AS HISTAMINE-3 ANTAGONISTS (Fri, 20 Mar 2009)
The present invention provides a compound of formula (I) and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor. </p>
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METHODS AND COMPOSITIONS FOR TREATING AND MONITORING TREATMENT OF IL-13-ASSOCIATED DISORDERS (Fri, 13 Mar 2009)
<p id="p-0001-en" num="0000">Methods and compositions for reducing or inhibiting, or preventing or delaying the onset of, one or more symptoms associated with an early and/or a late phase of an IL-13-associated disorder or condition using IL-13 binding agents are disclosed. Methods for evaluating the kinetics and/or efficacy of an IL-13 binding agent in treating or preventing an IL-13-associated disorder or condition in a subject, e.g., a human subject, are also disclosed.</p>
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6-substituted 2-(benzimidazolyl)purine and purinone derivatives for immunosuppression (Fri, 13 Mar 2009)
<p id="p-0001" num="0000">The present invention provides novel purinones and purines useful for the prevention and treatment of autoimmune diseases, inflammatory disease, mast cell mediated disease and transplant rejection. The compounds are of the general formulae I and II shown below, in which Q is selected from the group consisting of CX and nitrogen; and A is chosen from the group consisting of H, (C<sub>1</sub>-C<sub>6</sub>) alkyl, heteroaryl, and aryl:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="69.60mm" wi="61.72mm" file="US07902187-20110308-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> </p>
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ISOQUINOLINYL AND ISOINDOLINYL DERIVATIVES AS HISTAMINE-3 ANTAGONISTS (Fri, 13 Mar 2009)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="30.06mm" wi="62.65mm" file="us20090069300a1-20090312-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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Kv1.5 potassium channel inhibitors (Fri, 13 Mar 2009)
<p id="p-0001-en" num="0000">The present invention relates to 1-N-amino-2-imidazolidinones and derivatives thereof which are effective as Kv1.5 potassium channel inhibitors providing atrial-selective antiarrhythmic agents. The present invention further relates to compositions comprising said Kv1.5 potassium channel inhibitors, and to methods for treating cardiac arrhythmia.</p>
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AZACYCLYLISOQUINOLINONE AND ISOINDOLINONE DERIVATIVES AS HISTAMINE-3 ANTAGONISTS (Fri, 13 Mar 2009)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="26.75mm" wi="61.47mm" file="us20090069370a1-20090312-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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Methods and compositions for selectin inhibition (Fri, 13 Mar 2009)
<p id="p-0001" num="0000">The present invention relates to the field of anti-inflammatory substances, and more particularly to novel compounds that act as antagonists of the mammalian adhesion proteins known as selectins. In some embodiments, methods for treating selectin mediated disorders are provided which include administration of compound of Formula I:</p> <p id="p-0002" num="0000"><chemistry id="CHEM-US-00001" num="00001"> <img id="EMI-C00001" he="23.62mm" wi="69.85mm" file="US07994333-20110809-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <br/> wherein the constituent variables are defined herein. </p>
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COMPOSITIONS AND METHODS EMPLOYING NMDA ANTAGONISTS FOR ACHIEVING AN ANESTHETIC-SPARING EFFECT (Fri, 06 Mar 2009)
<p id="p-0001-en" num="0000">Provided herein are compositions, combinations, and methods comprising NMDA antagonists including, but not limited to, NMDA glutamate receptor antagonists such as [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1-(7)-en-2-yl)alkyl]phosphonic acid and derivatives thereof, which are effective in reducing the amount of anesthetic required to maintain anesthesia (i.e. to achieve an anesthetic-sparing effect).</p>
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COMPOSITIONS AND METHODS EMPLOYING NMDA ANTAGONISTS FOR ACHIEVING AN ANESTHETIC-SPARING EFFECT (Fri, 06 Mar 2009)
Provided herein are compositions, combinations, and methods comprising NMDA antagonists including, but not limited to, NMDA glutamate receptor antagonists such as [2-(8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1-(7)-en-2-yl)alkyl]phosphonic acid and derivatives thereof, which are effective in reducing the amount of anesthetic required to maintain anesthesia (i.e. to achieve an anesthetic-sparing effect).
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COMPOSITIONS AND METHODS EMPLOYING NMDA ANTAGONISTS FOR ACHIEVING AN ANESTHETIC-SPARING EFFECT (Fri, 06 Mar 2009)
Provided herein are compositions, combinations, and methods comprising NMDA antagonists including, but not limited to, NMDA glutamate receptor antagonists such as [2-(8,9-dioxo-2,6- diazabicyclo[5.2.0]non-1-(7)-en-2-yl)alkyl]phosphonic acid and derivatives thereof, which are effective in reducing the amount of anesthetic required to maintain anesthesia (i.e. to achieve an anesthetic-sparing effect). </p>
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NAPHTHYLPYRIMIDINE, NAPHTHYLPYRAZINE AND NAPHTHYLPYRIDAZINE ANALOGS AND THEIR USE AS AGONISTS OF THE WNT-BETA-CATENIN CELLULAR MESSAGING SYSTEM (Fri, 27 Feb 2009)
<p id="p-0001-en" num="0000">The present invention relates to naphthylpyrimidine analogs, methods of making naphthylpyrimidine analogs, compositions comprising a naphthylpyrimidine analog, and methods for treating canonical Wnt-β-catenin cellular messaging system-related disorders comprising administering to a subject in need thereof an effective amount of a naphthylpyrimidine, naphthylpyrazine and naphthylpyridazine analog.</p>
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SUBSTITUTED HETEROARYL BENZOFURAN ACIDS (Fri, 27 Feb 2009)
<p id="p-0001-en" num="0000">The present invention relates generally to substituted heteroaryl benzofuran acids and methods of using them.</p>
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Coupling process for generating reactive boron-containing derivatives of N-substituted pyrrole-2-carbonitriles to produce biaryls (Fri, 27 Feb 2009)
<p id="p-0001" num="0000">A convenient preparation of boron-containing compounds, borate salts, pyrrolecarbonitrile boron-containing compounds, N-substituted-pyrrole-2-carbonitrile boron-containing compounds, and derivatives thereof is provided. The present invention also provides for the use of these boron-containing compounds and derivatives thereof in coupling reactions to provide bi-aryl compounds.</p>
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NAPHTHYLPYRIMIDINE, NAPHTHYLPYRAZINE AND NAPHTHYLPYRIDAZINE ANALOGS AND THEIR USE AS AGONISTS OF THE WNT-BETA-CATENIN CELLULAR MESSAGING SYSTEM (Fri, 27 Feb 2009)
The present invention relates to naphthylpyrimidine analogs, methods of making naphthylpyrimidine analogs, compositions comprising a naphthylpyrimidine analog, and methods for treating canonical Wnt-[beta-symbol]-catenin cellular messaging system-related disorders comprising administering to a subject in need thereof an effective amount of a naphthylpyrimidine, naphthylpyrazine and naphthylpyridazine analog.
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NAPHTHYLPYRIMIDINE, NAPHTHYLPYRAZINE AND NAPHTHYLPYRIDAZINE ANALOGS AND THEIR USE AS AGONISTS OF THE WNT-BETA-CATENIN CELLULAR MESSAGING SYSTEM (Fri, 27 Feb 2009)
The present invention relates to naphthylpyrimidine analogs, methods of making naphthylpyrimidine analogs, compositions comprising a naphthylpyrimidine analog, and methods for treating canonical Wnt-[beta-symbol]-catenin cellular messaging system-related disorders comprising administering to a subject in need thereof an effective amount of a naphthylpyrimidine, naphthylpyrazine and naphthylpyridazine analog.
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NAPHTHYLPYRIMIDINE, NAPHTHYLPYRAZINE AND NAPHTHYLPYRIDAZINE ANALOGS AND THEIR USE AS AGONISTS OF THE WNT-BETA-CATENIN CELLULAR MESSAGING SYSTEM (Fri, 27 Feb 2009)
The present invention relates to naphthylpyrimidine analogs, methods of making naphthylpyrimidine analogs, compositions comprising a naphthylpyrimidine analog, and methods for treating canonical Wnt-[beta-symbol]-catenin cellular messaging system-related disorders comprising administering to a subject in need thereof an effective amount of a naphthylpyrimidine, naphthylpyrazine and naphthylpyridazine analog. </p>
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N-BENZOYL-PYRROLIDIN-3-YLAMINES AS HISTAMINE-3 ANTAGONISTS (Thu, 26 Feb 2009)
The present invention provides a compound of Formula (I) and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.
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Inhibitors of Protein Tyrosine Phosphatase 1B (Fri, 20 Feb 2009)
<p id="p-0001-en" num="0000">Protein tyrosine phosphatases (PTPases) such as PTP1B can play a role in regulating a wide variety of cellular responses such as insulin signaling. Substituted bicyclic fused-thiophene compounds can inhibit PTP1B and thereby induce greater insulin sensitivity. Accordingly, PTP1B inhibition can provide an alternate treatment for PTPase-mediated disorders such as diabetes.</p>
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PYRIMIDINE SULFONAMIDE ANALOGS AND THEIR USE AS AGONISTS OF THE WNT-BETA-CATENIN CELLULAR MESSAGING SYSTEM (Fri, 20 Feb 2009)
<p id="p-0001-en" num="0000">The present invention relates to pyrimidine sulfonamide analogs, methods of making pyrimidine sulfonamide analogs, compositions comprising a pyrimidine sulfonamide analog, and methods for treating canonical Wnt-β-catenin cellular messaging system-related disorders comprising administering to a subject in need thereof an effective amount of a pyrimidine sulfonamide analog.</p>
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Amino-5-[4-(difluoromethoxy)phenyl]-5-phenylimidazolone compounds for the inhibition of beta-secretase (Fri, 20 Feb 2009)
<p id="p-0001-en" num="0000">The present invention provides compounds and methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.</p>
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ANTIDEPRESSANT HETEROARYL DERIVATIVES OF HETEROCYCLE-FUSED BENZODIOXANS (Fri, 13 Feb 2009)
<p id="p-0001-en" num="0000">The invention provides compounds of the Formula:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="24.13mm" wi="69.85mm" file="us20090042874a1-20090212-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">that are useful for the treatment of depression (including but not limited to major depressive disorder, childhood depression and dysthymia), anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (also known as pre-menstrual syndrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa, bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction and related illnesses.</p>
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Antidepressant Piperidine Derivatives of Heterocycle-Fused Benzodioxans (Fri, 13 Feb 2009)
<p id="p-0001-en" num="0000">Compounds of the Formula:</p> <p id="p-0002-en" num="0000"/> <p id="p-0003-en" num="0000">are useful for the treatment of depression (including but not limited to major depressive disorder, childhood depression and dysthymia), anxiety, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder (also known as pre-menstrual syndrome), attention deficit disorder (with and without hyperactivity), obsessive compulsive disorder, social anxiety disorder, generalized anxiety disorder, obesity, eating disorders such as anorexia nervosa and bulimia nervosa, vasomotor flushing, cocaine and alcohol addiction, sexual dysfunction and related illnesses.</p>
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DIPHENYLIMIDAZOLYL COMPOUNDS AS INHIBITORS OF beta-SECRETASE (Fri, 13 Feb 2009)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I and the use thereof for the therapeutic treatment, prevention or amelioration of a disease or disorder characterized by elevated β-amyloid deposits or β-amyloid levels in a patient.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="40.47mm" wi="63.67mm" file="us20090042912a1-20090212-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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AMINO-5-(6-MEMBERED)HETEROARYLIMIDAZOLONE COMPOUNDS AND THE USE THEREOF FOR BETA-SECRETASE MODULATION (Fri, 13 Feb 2009)
<p id="p-0001-en" num="0000">The present invention provides a 2-amino-5-heteroaryl-5-phenylimidazolone compound of formula I</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="39.71mm" wi="69.85mm" file="us20090042908a1-20090212-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles</p>
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AMINO-5-[SUBSTITUTED-4-(DIFLUOROMETHOXY)PHENYL]-5-PHENYLIMIDAZOLONE COMPOUNDS AS BETA-SECRETASE INHIBITORS (Fri, 13 Feb 2009)
<p id="p-0001-en" num="0000">The present invention provides a 2-amino-5-[substituted-4-(difluoromethoxy)phenyl]-5-phenylimidazolone compound of formula I</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="42.33mm" wi="69.85mm" file="us20090042964a1-20090212-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.</p>
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IDENTIFICATION AND CHARACTERIZATION OF HCV REPLICON VARIANTS WITH REDUCED SUSCEPTIBILITY TO A COMBINATION OF POLYMERASE AND PROTEASE INHIBITORS, AND METHODS RELATED THERETO (Fri, 13 Feb 2009)
The present invention provides methods of decreasing the frequency of emergence, decreasing the level of resistance, and delaying the emergence of a treatment-resistant hepatitis C viral infection, by administering to a subject, either in combination or in series, an inhibitor of the hepatitis C RNA-dependent RNA polymerase NS5B, e.g., a benzofuran, such as 5-cyclopropyl-2-(4-fluorophenyl)- 6-[(2-hydroxyethyl)(methylsulfonyl)amino]-N-methyl-l-benzofuran- 3-carboxamide (HCV-796), and an inhibitor of the serine protease NS3, e.g., boceprevir. Additionally, the invention relates to methods of monitoring the course of treatment of a hepatitis C viral infection, methods of monitoring and prognosing a hepatitis C viral infection, and methods of identifying an individual with a decreased likelihood of responding to an anti-hepatitis C viral therapy. These methods use the sequence(s) of HCV nonstructural gene(s) to identify the emergence of a treatment-resistant hepatitis C viral infection, particularly a benzofuran (e.g., HCV-796) and NS3 inhibitor (e.g., boceprevir) treatment- resistant hepatitis C viral infection.
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QUINAZOLINE COMPOUNDS (Fri, 13 Feb 2009)
This invention relates generally to quinazoline-based modulators of Liver X receptors (LXRs) and related methods.
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QUINAZOLINE COMPOUNDS (Fri, 13 Feb 2009)
This invention relates generally to quinazoline-based modulators of Liver X receptors (LXRs) and related methods.</p>
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METHODS OF DETECTION OF AMYLOIDOGENIC PROTEINS (Thu, 12 Feb 2009)

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3-aryl-4-hydroxyfuranone compounds and the human and animal health use thereof (Fri, 06 Feb 2009)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I and the use thereof for the inhibition of bacterial cell wall biosynthesis and for the therapeutic treatment of bacterial infection or disease in a patient in need thereof. The present invention also provides the use of the formula I compound for the control of ecto- or endoparasites in homeothermic animals.</p> <p id="p-0002-en" num="0000"/>
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Quinoline Intermediates of Receptor Tyrosine Kinase Inhibitors and the Synthesis Thereof (Fri, 30 Jan 2009)
<p id="p-0001-en" num="0000">This invention is directed to methods of preparing 4-substituted quinoline compounds as intermediates in the manufacture of receptor tyrosine kinase inhibitors and intermediate compounds used in the methods thereof, wherein the 4-substituted quinoline compound has the following general formula (I):</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="27.60mm" wi="69.85mm" file="us20090030197a1-20090129-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">wherein substitutions at LG″, PG, A, G, R<sub>1 </sub>and R<sub>4 </sub>are set forth in the specification.</p>
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Aminoalkylazole derivatives as histamine-3 antagonists (Fri, 23 Jan 2009)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula Ia:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="43.35mm" wi="73.07mm" file="US07803825-20100928-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001-en" list-style="none"> <li> <ul id="ul0002-en" list-style="none"> <li>and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.</li> </ul> </li> </ul> </p>
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INHIBITORS OF BETA AMYLOID PRODUCTION (Fri, 23 Jan 2009)
<p id="p-0001-en" num="0000">Novel sulfonamide compounds useful in the treatment of conditions related to the production of beta-amyloid are described, as are routes to their preparation. The sulfonamide compounds are of the following structure, wherein R<sub>1</sub>-R<sub>3 </sub>are defined herein. Also provided are pharmaceutical compositions containing these compounds and/or prodrugs of these compounds and a physiologically compatible carrier. These compounds are specifically useful for inhibiting beta amyloid production, and treating Alzheimer's Disease, amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, mild cognitive impairment (MCI) and Down's syndrome.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="19.47mm" wi="25.74mm" file="us20090023801a1-20090122-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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PROCESSES AND INTERMEDIATES FOR THE PREPARATION OF HETEROCYCLIC SULFONAMIDE COMPOUNDS (Fri, 23 Jan 2009)
<p id="p-0001-en" num="0000">Methods for preparing compound of formula (I) are described, wherein R<sub>1</sub>-R<sub>3 </sub>are defined herein, as are methods for preparing the intermediates formed therein.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="27.60mm" wi="49.28mm" file="us20090023930a1-20090122-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">Also described are methods for enantioselectively preparing a chiral compound of the following structure, wherein R<sub>2 </sub>and R<sub>3 </sub>are defined herein.</p> <p id="p-0004-en" num="0000"> <chemistry id="chem-us-00002-en" num="00002"> <img id="emi-c00002" he="13.21mm" wi="17.70mm" file="us20090023930a1-20090122-c00002.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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INHIBITORS OF BETA AMYLOID PRODUCTION (Fri, 23 Jan 2009)
Novel sulfonamide compounds useful in the treatment of conditions related to the production of beta-amyloid are described, as are routes to their preparation. The sulfonamide compounds are of the following structure, wherein R4-R3 are defined herein. Also provided are pharmaceutical compositions containing these compounds and/or prodrugs of these compounds and a physiologically compatible carrier. These compounds are specifically useful for inhibiting beta amyloid production, and treating Alzheimer's Disease, amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, mild cognitive impairment (MCI) and Down's syndrome.
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AMINOALKYLAZOLE DERIVATIVES AS HISTAMINE-3 ANTAGONISTS (Fri, 23 Jan 2009)
The present invention provides a compound of formula (I) and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor.
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PROCESSES AND INTERMEDIATES FOR THE PREPARATION OF HETEROCYCLIC SULFONAMIDE COMPOUNDS (Fri, 23 Jan 2009)
Methods for preparing compound of Formula (I) are described, wherein R1-R3 are defined herein, as are methods for preparing the intermediates formed therein. Formula (I) Also described are methods for enantioselectively preparing a chiral compound of the following structure, wherein R2 and R3 are defined herein. Formula (II).
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SQUARATE KINASE INHIBITORS (Fri, 23 Jan 2009)
The present application provides compounds of Formula (I): and pharmaceutically acceptable salts thereof and pharmaceutical compositions thereof, wherein Het, R4, R9, and R10 are defined herein. Compounds of formula (I) are useful as inhibitors of MAP kinase activated protein kinase 2 (MK2).
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AMINOALKYLAZOLE DERIVATIVES AS HISTAMINE-3 ANTAGONISTS (Fri, 23 Jan 2009)
The present invention provides a compound of formula (I) and the use thereof for the treatment of a central nervous system disorder related to or affected by the histamine-3 receptor. </p>
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INHIBITORS OF BETA AMYLOID PRODUCTION (Fri, 23 Jan 2009)
Novel sulfonamide compounds useful in the treatment of conditions related to the production of beta-amyloid are described, as are routes to their preparation. The sulfonamide compounds are of the following structure, wherein R4-R3 are defined herein. Also provided are pharmaceutical compositions containing these compounds and/or prodrugs of these compounds and a physiologically compatible carrier. These compounds are specifically useful for inhibiting beta amyloid production, and treating Alzheimer's Disease, amyloid angiopathy, cerebral amyloid angiopathy, systemic amyloidosis, hereditary cerebral hemorrhage with amyloidosis of the Dutch type, inclusion body myositis, mild cognitive impairment (MCI) and Down's syndrome. </p>
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Novel Succinate Salt of O-Desmethyl-Venlafaxine (Fri, 16 Jan 2009)
<p id="p-0001-en" num="0000">A novel salt of O-desmethyl venlafaxine is provided, O-desmethylvenlafaxine succinate. Pharmaceutical compositions, dosage forms and methods of use are also provided.</p>
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Processes For Preparing Bicyclic Oxazine Carboxaldehyde and Beta-Lactamase Inhibitors (Fri, 16 Jan 2009)
<p id="p-0001-en" num="0000">The invention relates to processes for the preparation of the bicyclic oxazine carboxaldehyde Compound 1:</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="18.63mm" wi="53.42mm" file="us20090018332a1-20090115-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">The invention also relates to the use of Compound 1 in the preparation of □-lactamase inhibitors.</p>
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AMINO-5-[4-(DIFLUOROMETHOXY) PHENYL]-5-PHENYLIMIDAZOLONE COMPOUNDS FOR THE INHIBITION OF BETA-SECRETASE (Fri, 09 Jan 2009)
<p id="p-0001-en" num="0000">The present invention provides a 2-amino-5-[4-(difluoromethoxy)phenyl]-5-phenylimidazolone compound of formula I</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001-en" he="39.37mm" wi="69.85mm" file="us20090012139a1-20090108-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p> <p id="p-0003-en" num="0000">The present invention also provides methods for the use thereof to inhibit β-secretase (BACE) and treat β-amyloid deposits and neurofibrillary tangles.</p>
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PROCESSES FOR PREPARING BICYCLIC OXAZINE CARBOXALDEHYDE AND BETA-LACTAMASE INHIBITORS (Fri, 09 Jan 2009)
The invention relates to processes for the preparation of the bicyclic oxazine carboxaldehyde Compound 1: (I) The invention also relates to the use of Compound 1 in the preparation of β-lactamase inhibitors.
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ETHERS OF O-DESMETHYL VENLAFAXINE, PROCESS FOR THEIR PREPARATION AND THEIR USE FOR MANUFACTURING MEDICAMENTS (Tue, 30 Dec 2008)

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Tricyclic 6-alkylidene-penems as β-lactamase inhibitors (Fri, 26 Dec 2008)
<p id="p-0001-en" num="0000">The present invention provides a compound of formula I, pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof,</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="25.74mm" wi="45.30mm" file="US07691842-20100406-C00001.TIF" alt="embedded image" img-content="chem" img-format="tif"/> </chemistry> <ul id="ul0001-en" list-style="none"> <li> <ul id="ul0002-en" list-style="none"> <li>wherein one of A and B denotes hydrogen and the other an optionally substituted fused tricyclic heteroaryl group; and X is O.</li> </ul> </li> </ul> </p>
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SUBSTITUTED SULFONAMIDE-INDOLES (Fri, 26 Dec 2008)
<p id="p-0001-en" num="0000">The present invention relates generally to substituted sulfonamide indoles such as substituted sulfonamide indoles, and methods of using them.</p>
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PROCESS FOR THE SYNTHESIS OF PROGESTERONE RECEPTOR MODULATORS (Fri, 26 Dec 2008)
<p id="p-0001-en" num="0000">Processes for preparing substituted oxindole-2-ones, and specifically the following, are described, wherein R<sup>1</sup>-R<sup>4</sup>, R<sup>6</sup>, and n are defined herein. The processes include reacting a first alkali metal hydroxide, a tetraalkyl ammonium salt, a benzonitrile, and R<sup>6</sup>X or XCH<sub>2</sub>(CH<sub>2</sub>)<sub>n</sub>X′, wherein R<sup>6 </sup>is C<sub>1 </sub>to C<sub>6 </sub>alkyl, substituted C<sub>1 </sub>to C<sub>6 </sub>alkyl, C<sub>3 </sub>to C<sub>8 </sub>cycloalkyl, substituted C<sub>3 </sub>to C<sub>8 </sub>cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, or substituted heterocyclic, X and X′ are, independently, leaving groups, and n is 1 to 5; (ii) reacting the product of step (i) with a second alkali metal hydroxide at a temperature of at least about 60° C.; (iii) reacting the product of step (ii) with an alkali alkoxide at a temperature of at least about 140° C. to form an oxindol-2-one; (iv) brominating the oxindol-2-one; and (v) coupling the brominated oxindol-2-one with a coupling reagent.</p> <p id="p-0002-en" num="0000"> <chemistry id="chem-us-00001-en" num="00001"> <img id="emi-c00001" he="59.94mm" wi="74.17mm" file="us20080319204a1-20081225-c00001.tif" img-content="chem" img-format="tif"/> </chemistry> </p>
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METHOD FOR TREATING ADAMTS-5-ASSOCIATED DISEASE (Fri, 19 Dec 2008)
<p id="p-0001-en" num="0000">The present invention relates to methods of treating ADAMTS-5-associated diseases and particularly osteoarthritis comprising administering an agent capable of modulating ADMATS-5 activity to a subject afflicted with the disease. The agent is preferably a biaryl sulfonamide compound. The invention is based, in part, on the discovery that transgenic animals that do not express functional ADAMTS-5 show a reduction in the degree of osteoarthritis after the induction of osteoarthritis as compared to WT animals. Furthermore, the ADAMTS-5 transgenic animals have reduced aggrecanase activity in articular tissue as compared to WT animals. These animals are good models for ADAMTS-5-associated diseases, and for screening of drugs useful in the treatment and/or prevention of these diseases. There are no other animal models in which the deletion of the activity of a single gene is capable of abrogating the course of osteoarthritis. Accordingly, these animals also show that osteoarthritis can be prevented and/or treated by administering to a subject an ADAMTS-5 inhibitory agent and particularly an agent capable of inhibiting the aggrecanase activity of ADAMTS-5.</p>
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