- MACROCYCLIC ANTAGONISTS OF THE MOTILIN RECEPTOR FOR TREATMENT OF GASTROINTESTINAL DYSMOTILITY DISORDERS
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The present invention provides conformationally-defined macrocyclic compounds that bind to and/or are functional modulators of the motilin receptor including subtypes, isoforms and/or variants thereof. These macrocyclic compounds, at a minimum, possess adequate pharmacological properties to be useful as therapeutics for a range of disease indications. In particular, these compounds are useful for treatment and prevention of disorders characterized by hypermotilinemia and/or gastrointestinal hypermotility, including, but not limited to, diarrhea, cancer treatment-related diarrhea, cancer-induced diarrhea, chemotherapy-induced diarrhea, radiation enteritis, radiation-induced diarrhea, stress-induced diarrhea, chronic diarrhea, AIDS-related diarrhea, C. difficile associated diarrhea, traveller's diarrhea, diarrhea induced by graph versus host disease, other types of diarrhea, dyspepsia, irritable bowel syndrome, chemotherapy-induced nausea and vomiting (emesis) and post-operative nausea and vomiting and functional gastrointestinal disorders. In addition, the compounds possess utility for the treatment of diseases and disorders characterized by poor stomach or intestinal absorption, such as short bowel syndrome, celiac disease and cachexia. The compounds also have use for the treatment of inflammatory diseases and disorders of the gastrointestinal tract, such as inflammatory bowel disease, ulcerative colitis, Crohn's disease and pancreatitis. Accordingly, methods of treating such disorders and pharmaceutical compositions including compounds of the present invention are also provided.
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Page/Page column 39
(2010/04/30)
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- Phosphate/sulfate ester compounds and pharmaceutical composition for inhibiting protein interacting NIMA (PIN1)
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Phosphate/sulfate ester compounds that modulate and/or inhibit the activity of protein interacting NIMA (PIN1), and to pharmaceutical compositions containing such compounds are described. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating disorders characterized by hypertension, inappropriate cell proliferation, infectious diseases, and neurodegenerative brain disorders, by administering effective amounts of such compounds.
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Page/Page column 51
(2010/02/14)
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- PHOSPHATE/SULFATE ESTER COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS FOR INHIBITING PROTEIN INTERACTING NIMA (PIN1)
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Phosphate/sulfate ester compounds that modulate and/or inhibit the activity of protein interacting NIMA (PIN1), and to pharmaceutical compositions containing such compounds are described. The invention is also directed to the therapeutic or prophylactic use of such compounds and compositions, and to methods of treating disorders characterized by hypertension, inappropriate cell proliferation, infectious diseases, and neurodegenerative brain disorders, by administering effective amounts of such compounds.
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- An efficient synthesis of enantiomerically enriched aryllactic esters
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An efficient synthesis of enantiomerically enriched aryllactic esters or acids has been established. Darzen's condensation of arylaldehydes with ethyl chloroacetate followed by catalytic hydrogenation gave racemic aryllactic esters. Enzyme catalyzed (lipa
- Lefker, Bruce A.,Hada, William A.,McGarry, Patrick J.
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p. 5205 - 5208
(2007/10/02)
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