| Literature DB >> 16078829 |
Zhiqiang Guo1, John E Tellew, Raymond S Gross, Brian Dyck, Jonathan Grey, Mustapha Haddach, Mehrak Kiankarimi, Marion Lanier, Bin-Feng Li, Zhiyong Luo, James R McCarthy, Manisha Moorjani, John Saunders, Robert Sullivan, Xiaohu Zhang, Said Zamani-Kord, Dimitri E Grigoriadis, Paul D Crowe, Ta Kung Chen, John P Williams.
Abstract
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.Entities:
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Year: 2005 PMID： 16078829 DOI： 10.1021/jm050384+
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446