Bioorganic & Medicinal Chemistry Letters 2010-10-15

A class of novel conjugates of substituted purine and Gly-AA-OBzl: synthesis and evaluation of orally analgesic activity.

Guifeng Kang, Ming Zhao, Xiaoyi Zhang, Li Peng, Chunbo Li, Wei Mao, Weidong Ye, Shiqi Peng

Index: Bioorg. Med. Chem. Lett. 20 , 6157-60, (2010)

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Abstract

Aimed at the chemotherapy of chronic pain two kinds of analgesic pharmacophores, substituted purine and Gly-AA-OBzl, were coupled via a five-step-reaction procedure and 19 novel conjugates N-[2-chloro-9-(tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters were provided. On mouse-tail flick model their in vivo analgesic activities were assayed. The results indicate that introducing Gly-OC(2)H(5) into the 6-position of the substituted purine leads to ambiguous increase of the analgesic activity, while introducing Gly-AA-OBzl into this position leads to significant increase of the analgesic activity.Copyright © 2009. Published by Elsevier Ltd.


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