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

作者：Guo ZQ^*; Tellew JE; Gross RS; Dyck B; Grey J; Haddach M; Kiankarimi M; Lanier M; Li BF; Luo ZY; McCarthy JR; Moorjani M; Saunders J; Sullivan R; Zhang XH; Zamani Kord S; Grigoriadis DE; Crowe PD; Chen TK; Williams JP

来源：Journal of Medicinal Chemistry, 2005, 48(16): 5104-5107.

DOI：10.1021/jm050384+

The synthesis and SAR studies of tricyclic imidazo[4,5-b]pyridin-2-ones as human corticotropin-releasing factor receptor (CRF1) 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 CRF1 antagonists with improved pharmacokinetics properties, 16g exhibited a favorably lower volume of distribution.

• 出版日期2005-8-11