Journal
BIOORGANIC & MEDICINAL CHEMISTRY
Volume 14, Issue 8, Pages 2589-2599Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2005.11.040
Keywords
non-steroidal anti-inflammatory drug (NSAID); nitric oxide; naproxen; CINOD; anit-inflammatory; cyclo-oxygenase
Ask authors/readers for more resources
A series of glycolamide naproxen prodrugs containing a nitrate group as a nitric oxide (NO) donor moiety has been synthesized. These Compounds were evaluated for their anti-inflammatory activity, naproxen release, and gastric tolerance. Compounds 4a, 4b, 5a, 5b, 7b, and 7c exhibited anti-inflammatory activity equivalent to that of the parent NSAID, naproxen-Na, in the rat carrageenan paw edema model. At equimolar doses relative to naproxen-Na. the NO-donor glycolamide derivatives 4a, 4b, 5a.. 5b, 7b, and 7c were gastro-sparing in the rat. Naproxen formation from these NO-donor glycolamides varied among the structures examined, with the N-substituent on the amide group having a particular influence, and demonstrated their prodrug nature. Compound 7b was selected for exemplary demonstration that the glycolamide nitrates can be bioactivated to release NO. These data open the possibility that naproxen glycolainide nitrates may represent a safer alternative to naproxen as anti-inflammatory medicines. (c) 2005 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available