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1: J Med Chem. 2005 Aug 11;48(16):5104-7.Click here to read Links

Design and synthesis of tricyclic imidazo[4,5-b]pyridin-2-ones as corticotropin-releasing factor-1 antagonists.

Guo Z, Tellew JE, Gross RS, Dyck B, Grey J, Haddach M, Kiankarimi M, Lanier M, Li BF, Luo Z, McCarthy JR, Moorjani M, Saunders J, Sullivan R, Zhang X, Zamani-Kord S, Grigoriadis DE, Crowe PD, Chen TK, Williams JP.

Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA. zguo@neurocrine.com

The synthesis and SAR studies of tricyclic imidazo[4,5-b]pyridin-2-ones as human corticotropin-releasing factor receptor (CRF(1)) antagonists are discussed herein. Compound 16g was identified as a functional antagonist that inhibited CRF-stimulated cyclic adenosine monophosphate production and CRF-induced adrenocorticotrophic hormone release. Pharmacokinetics studies in rats showed that 16g was orally bioavailable, had good brain penetration, and had a moderate half-life. In our effort to identify CRF(1) antagonists with improved pharmacokinetics properties, 16g exhibited a favorably lower volume of distribution.

PMID: 16078829 [PubMed - indexed for MEDLINE]

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