Bioorganic & Medicinal Chemistry 2004-11-15

Synthesis and biological evaluation of some 6-arylamidomorphines as analogues of morphine-6-glucuronide.

James M Macdougall, Xiao-Dong Zhang, Willma E Polgar, Taline V Khroyan, Lawrence Toll, John R Cashman

Index: Bioorg. Med. Chem. 12(22) , 5983-90, (2004)

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Abstract

A series of 6-beta-arylamidomorphines was synthesized and biologically evaluated. Various aryl substituents were introduced into the arylamidomorphines to examine substituent structure-activity relationships. Competition binding assays showed that compounds 10a-h bound to the mu opioid receptor with high affinity (0.2-0.6 nM). Functional assays showed that compounds 10a-h acted as full mu opioid receptor agonists. The ED(50) of compound 10e.HCl as an analgesic was 12.6 mg/kg in the tail flick latency test in the rat.


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