Comparative molecular field analysis of fenoterol derivatives: A platform towards highly selective and effective beta(2)-adrenergic receptor agonists.

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Jozwiak K, Woo AY, Tanga MJ, Toll L, Jimenez L, Kozocas JA, Plazinska A, Xiao RP, Wainer IW

Comparative molecular field analysis of fenoterol derivatives: A platform towards highly selective and effective beta(2)-adrenergic receptor agonists.

Bioorg Med Chem. 2010 Jan 15;18(2):728-36. doi: 10.1016/j.bmc.2009.11.062. Epub 2009 Dec 6.

PubMed ID

20036561 [ View in PubMed

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Abstract

PURPOSE: To use a previously developed CoMFA model to design a series of new structures of high selectivity and efficacy towards the beta(2)-adrenergic receptor. RESULTS: Out of 21 computationally designed structures 6 compounds were synthesized and characterized for beta(2)-AR binding affinities, subtype selectivities and functional activities. CONCLUSION: the best compound is (R,R)-4-methoxy-1-naphthylfelnoterol with K(i)beta(2)-AR=0.28microm, K(i)beta(1)-AR/K(i)beta(2)-AR=573, EC(50cAMP)=3.9nm, EC(50cardio)=16nm. 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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Salmeterol	Beta-1 adrenergic receptor	Ki (nM)	2300	N/A	N/A	Details