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

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

  • J Med Chem. 2005 Aug 11;48(16):5104-7. doi: 10.1021/jm050384+.
Zhiqiang Guo 1,  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
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA. zguo@neurocrine.com
PMID: 16078829 DOI: 10.1021/jm050384+
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.

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