2. Academic Validation
  3. 2-aryloxy-4-alkylaminopyridines: discovery of novel corticotropin-releasing factor 1 antagonists

2-aryloxy-4-alkylaminopyridines: discovery of novel corticotropin-releasing factor 1 antagonists

  • J Med Chem. 2008 Mar 13;51(5):1385-92. doi: 10.1021/jm070579c.
Yuhpyng L Chen 1,  R Scott Obach,  John Braselton,  Michael L Corman,  James Forman,  Jody Freeman,  Randall J Gallaschun,  Robert Mansbach,  Anne W Schmidt,  Jeffrey S Sprouse,  F David Tingley Iii,  Elizabeth Winston,  David W Schulz
Affiliations

Affiliation

  • 1 Medicinal Chemistry Department, Pfizer, Inc., Groton, Connecticut 06340, USA. [email protected]
PMID: 18288792 DOI: 10.1021/jm070579c
Abstract

An orally active clinical candidate of corticotropin-releasing factor 1 (CRF 1) antagonist 1 showed a significant positive food effect in dog and human after oral administration. Efforts to address the food effect issue led us to explore and discover compounds in series 2 as orally active CRF 1 receptor antagonists, in which some compounds showed improved physicochemical properties while retaining desired pharmacological properties. Compound 3a (CP-376395) was selected for further development, due not only to its reduced food effects but also its greater efficacy in CNS models. Compound 3a was advanced to the clinic. The synthesis of representative potential candidates and their in vitro, ex vivo, and in vivo data are described.

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