Premium
Synthesis of Some Novel 2,6‐Disubstituted Pyridazin‐3(2 H )‐one Derivatives as Analgesic, Anti‐Inflammatory, and Non‐Ulcerogenic Agents
Author(s) -
Ibrahim Tamer H.,
Loksha Yasser M.,
Elshihawy Hosam A.,
Khodeer Dina M.,
Said Mohamed M.
Publication year - 2017
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201700093
Subject(s) - chemistry , analgesic , celecoxib , cyclooxygenase , isoindole , pyridazine , anti inflammatory , chemical synthesis , stereochemistry , pharmacology , selectivity , valdecoxib , in vitro , biochemistry , enzyme , catalysis , medicine , rofecoxib
Some novel 2,6‐disubstituted pyridazine‐3(2 H )‐one derivatives were synthesized and evaluated for in vitro cyclooxygenase‐2 (COX‐2) inhibitory efficacy. Compounds 2‐{[3‐(2‐methylphenoxy)‐6‐oxopyridazin‐1(6 H )‐yl]methyl}‐1 H ‐isoindole‐1,3(2 H )‐dione ( 5a ), 2 ‐ propyl‐6‐( o ‐tolyloxy)pyridazin‐3(2 H )‐one ( 6a ), and 2‐ benzyl‐6‐(3,5‐dimethyl‐1 H ‐pyrazol‐1‐yl)pyridazin‐3(2 H )‐one ( 16a ) showed the most potent COX‐2 inhibitory activity with IC 50 values of 0.19, 0.11, and 0.24 μM, respectively. The synthesized compounds with the highest COX‐2 selectivity indices were evaluated for their anti‐inflammatory, analgesic, and ulcerogenic activities. Compounds 6a and 16a demonstrated the most potent and consistent anti‐inflammatory activity over the synthesized compounds, which was significantly higher than that of celecoxib in the carrageenin rat paw edema model and with milder ulcer scoring than that of indomethacin in the ulcerogenicity screening.