Title of article :
Comparative molecular field analysis of fenoterol derivatives: A platform towards highly selective and effective β2-adrenergic receptor agonists Original Research Article
Author/Authors :
Krzysztof Jozwiak، نويسنده , , Anthony Yiu-Ho Woo، نويسنده , , Mary J. Tanga، نويسنده , , Lawrence Toll، نويسنده , , Lucita Jimenez، نويسنده , , Joseph A. Kozocas، نويسنده , , Anita Plazinska، نويسنده , , Rui-Ping Xiao، نويسنده , , Irving W. Wainer، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2010
Abstract :
Purpose: To use a previously developed CoMFA model to design a series of new structures of high selectivity and efficacy towards the β2-adrenergic receptor. Results: Out of 21 computationally designed structures 6 compounds were synthesized and characterized for β2-AR binding affinities, subtype selectivities and functional activities. Conclusion: the best compound is (R,R)-4-methoxy-1-naphthylfelnoterol with Kiβ2-AR = 0.28 μm, Kiβ1-AR/Kiβ2-AR = 573, EC50cAMP = 3.9 nm, EC50cardio = 16 nm. The CoMFA model appears to be an effective predictor of the cardiomocyte contractility of the studied compounds which are targeted for use in congestive heart failure.
Keywords :
Comparative molecular fields analysis , drug design , ?2 selective agonist
Journal title :
Bioorganic and Medicinal Chemistry
Journal title :
Bioorganic and Medicinal Chemistry
