- New bicyclic compounds as crac channel modulators
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The present invention relates to novel compounds which are inhibitors of CRAC channel activity. This invention also relates to pharmaceutical compositions containing them, process for their preparation and their use in therapy.
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Paragraph 0107
(2014/06/24)
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- Synthesis and structure-activity relationships of 8-(pyrid-3-yl)pyrazolo[1, 5-a]-1,3,5-triazines: Potent, orally bioavailable corticotropin releasing factor receptor-1 (CRF1) antagonists
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This report describes the syntheses and structure-activity relationships of 8-(substituted pyridyl)pyrazolo[1,5-a]-1,3,5-triazine corticotropin releasing factor receptor-1 (CRF1) receptor antagonists. These CRF1 receptor antagonists may be potential anxiolytic or antidepressant drugs. This research resulted in the discovery of compound 13-15, which is a potent, selective CRF1 antagonist (hCRF1 IC50 = 6.1 ± 0.6 nM) with weak affinity for the CRF-binding protein and biogenic amine receptors. This compound also has a good pharmacokinetic profile in dogs. Analogue 13-15 is orally effective in two rat models of anxiety: the defensive withdrawal (situational anxiety) model and the elevated plus maze test. Analogue 13-15 has been advanced to clinical trials.
- Gilligan, Paul J.,Clarke, Todd,He, Liqi,Lelas, Snjezana,Li, Yu-Wen,Heman, Karen,Fitzgerald, Lawrence,Miller, Keith,Zhang, Ge,Marshall, Anne,Krause, Carol,McElroy, John F.,Ward, Kathyrn,Zeller, Kim,Wong, Harvey,Bai, Steven,Saye, Joanne,Grossman, Scott,Zaczek, Robert,Arneric, Stephen P.,Hartig, Paul,Robertson, David,Trainor, George
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experimental part
p. 3084 - 3092
(2010/02/28)
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- New FBPase inhibitors for diabetes
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Compounds of formula as well as pharmaceutically acceptable salts and esters thereof, wherein R1 to R3 have the significance given in the application and which can be used in the form of pharmaceutical compositions.
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Page/Page column 21
(2008/06/13)
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- CRF ligands via Suzuki and Negishi couplings of 3-pyridyl boronic acids or halides with 2-benzyloxy-4-chloro-3-nitropyridine.
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A series of imidazo[4,5-b]pyridines with a 7-(3-pyridyl) substituent is described as high affinity CRF receptor ligands. Individual analogues were synthesized from key intermediates obtained via palladium-catalyzed coupling of 3-pyridyl zinc or boronic acid organometallic intermediates with 2-benzyloxy-4-chloro-3-nitropyridine 12.
- Arvanitis, Argyrios G,Arnold, Charles R,Fitzgerald, Lawrence W,Frietze, William E,Olson, Richard E,Gilligan, Paul J,Robertson, David W
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p. 289 - 291
(2007/10/03)
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