Synthesis and analgesic effect of normorphine-3- and -6-glucuronides.

Abstract

Normorphine-3- and -6-glucuronides were synthesized, and their analgesic effects were examined. Normorphine-3-glucuronide was obtained by condensation of normorphine with acetobromoglucuronate in the presence of sodium hydroxide in acetone. On the other hand, normorphine-6-glucuronide was synthesized by condensing N,O3-biscarbobenzoxynormorphine with acetobromoglucuronate in the presence of silver carbonate, and removing the protecting groups from the resultant reaction product by catalytic hydrogenation and solvolysis with sodium methoxide and barium hydroxide. The analgesic effect of normorphine-6-glucuronide (ED50 0.036 nmol/mice) was 125-fold more potent than that of normorphine in mice injected i.c.v. Normorphine-3-glucuronide was shown to be 37% effective at a dose of 2 nmol/mice, but induced convulsion at higher doses when given by i.c.v. injection.

• Authors: K Oguri, C K Kuo, H Yoshimura
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 37 Issue 4 Pg. 955-7 (Apr 1989) ISSN: 0009-2363 [Print] Japan
• PMID: 2569941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Morphine Derivatives
• normorphine-6-glucuronide
• normorphine-3-glucuronide

Topics

• Analgesics, Opioid (chemical synthesis)
• Animals
• Chemical Phenomena
• Chemistry
• Male
• Mice
• Mice, Inbred Strains
• Morphine Derivatives (chemical synthesis, pharmacology)