Pyridyl-phenyl ether monoamine reuptake inhibitors: Impact of lipophilicity on dual SNRI pharmacology and off-target promiscuity.

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作者信息

Whitlock Gavin A, Fish Paul V, Fray M Jonathan, Stobie Alan, Wakenhut Florian

机构信息

Pfizer Global Research and Development, Sandwich Laboratories, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK.

出版信息

Bioorg Med Chem Lett. 2008 May 1;18(9):2896-9. doi: 10.1016/j.bmcl.2008.03.082. Epub 2008 Apr 8.

DOI:10.1016/j.bmcl.2008.03.082

PMID:18417343

Abstract

A novel series of pyridyl-phenyl ethers are disclosed, which possess dual 5-HT and NA reuptake pharmacology with good selectivity over dopamine reuptake inhibition. An analysis of the relationship between lipophilicity and pharmacology highlighted that potent dual SNRI activity was only achievable at c log P>3.5. The series was found to possess significant polypharmacology issues, and we concluded that this off-target promiscuity was related to lipophilicity.

摘要

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