SELECTIVE CYCLOOXYGENASE INHIBITORS - NOVEL 4-SPIRO 1,2-DIARYLCYCLOPENTENES ARE POTENT AND ORALLY-ACTIVE COX-2 INHIBITORS

Authors
REITZ DB HUANG HC LI JJ GARLAND DJ MANNING RE ANDERSON GD GREGORY SA KOBOLDT CM PERKINS WE SEIBERT K ISAKSON PC
Citation
Db. Reitz et al., SELECTIVE CYCLOOXYGENASE INHIBITORS - NOVEL 4-SPIRO 1,2-DIARYLCYCLOPENTENES ARE POTENT AND ORALLY-ACTIVE COX-2 INHIBITORS, Bioorganic & medicinal chemistry letters, 5(8), 1995, pp. 867-872
Citations number
29
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
5
Issue
8
Year of publication
1995
Pages
867 - 872
Database
ISI
SICI code
0960-894X(1995)5:8<867:SCI-N4>2.0.ZU;2-V
Abstract
Novel 4,5-diarylspiro[2.4]hept-5-enes, 6,7-diarylspiro[3.4]oct-6-enes, and 2,3-diarylspiro[4.4]non-2-enes have been synthesized and shown to be very potent inducible cyclooxygenase (COX-2) inhibitors with inhib ition (IC50) in the low nanomolar range and enzyme selectivity ratios as high as four orders of magnitude. The methyl sulfone spiro[2.4]hept -5-ene 1 (SC-58451) was found to be orally active (ED(50) = 0.3 mpk) i n the rat adjuvant-induced arthritis model with no gastric lesions obs erved at 200 mpk.