(S,E)-N-[1-(3-heteroarylphenyl)ethyl]-3-(2-fluorophenyl)acrylamides: synthesis and KCNQ2 potassium channel opener activity.

作者信息

L'Heureux Alexandre, Martel Alain, He Huan, Chen Jie, Sun Li-Qiang, Starrett John E, Natale Joanne, Dworetzky Steven I, Knox Ronald J, Harden David G, Weaver David, Thompson Mark W, Wu Yong-Jin

机构信息

Department of Medicinal Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, 100 de l'Industrie Blvd., Candiac, Quebec, Canada, J5R 1J1.

出版信息

Bioorg Med Chem Lett. 2005 Jan 17;15(2):363-6. doi: 10.1016/j.bmcl.2004.10.065.

DOI:10.1016/j.bmcl.2004.10.065

PMID:15603955

Abstract

Replacement of the morpholinyl moiety in (S,E)-N-[1-(3-morpholinophenyl)ethyl]-3-phenylacrylamide (1) with heteroaryl groups led to the identification of (S,E)-N-1-[3-(6-fluoropyridin-3-yl)phenyl]ethyl-3-(2-fluorophenyl)acrylamide (5) as a potent KCNQ2 potassium channel opener. Among this series of heteroaryl substituted acrylamides, (S,E)-N-1-[3-(1H-pyrazol-1-yl)phenyl]ethyl-3-(2-fluorophenyl)acrylamide (9) exhibits balanced potency and efficacy. The syntheses and the KCNQ2 opener activity of this series of acrylamides are described.

摘要