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Bioorg Med Chem Lett. 2003 Mar 24;13(6):1207-14.

Structure-activity relationships of some opiate glycosides.

Author information

1
Ultrafine UFC Ltd, Synergy House, Guildhall Close, Manchester Science Park, Manchester M15 6SY, UK. stachuls@liverpool.ac.uk

Abstract

A number of analogues of morphine-6-glucuronide 1 have been prepared and evaluated as potential analgesic agents by competitive mu-receptor binding assay and in vivo antinociceptive activity. The analogues show variation in the nature of the carbohydrate residue, the N-substituent, the O(3)-substituent and saturation of the 7,8-double bond compared to 1. In general, only the 6beta-glucoside or beta-glucuronide carbohydrate residues showed potent agonism; other modified carbohydrates were less active or exhibited potential antagonism. Variations in N-substituent led to either reduced agonism (N-H) or potential antagonism [N-allyl, N-(cyclopropyl)methyl]; a polar N-substituent, carboxymethyl, failed to bind. Saturation of the 7,8-double bond led to increased agonism compared to the parent compound in all three examples studied.

PMID:
12643945
DOI:
10.1016/s0960-894x(03)00056-8
[Indexed for MEDLINE]

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