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Synthesis and biological screening of some novel 6‐substituted 2‐alkylpyridazin‐3(2 H )‐ones as anti‐inflammatory and analgesic agents
Author(s) -
Loksha Yasser M.,
AbdAlhaseeb Mohammad M.
Publication year - 2020
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.201900295
Subject(s) - diclofenac sodium , chemistry , analgesic , cyclooxygenase , selectivity , diclofenac , alkyl , hydrolysis , cyanide , edema , benzyl chloride , pharmacology , stereochemistry , medicinal chemistry , organic chemistry , enzyme , biochemistry , chromatography , catalysis , medicine , psychiatry
Some novel derivatives of 2‐alkyl 6‐substituted pyridazin‐3(2 H )‐ones were synthesized by condensation of 3,6‐dichloropyridazine with the sodium salt of benzyl cyanide, followed by hydrolysis and coupling with alkyl halides. The synthesized compounds were screened as cyclooxygenase (COX)‐1/COX‐2 inhibitors and as analgesic and anti‐inflammatory agents. Among the synthesized compounds, 6‐benzyl‐2‐methylpyridazin‐3(2 H )‐one ( 4a ), 6‐benzoyl‐2‐propylpyridazin‐3(2 H )‐one ( 8b ), and 6‐(hydroxy(phenyl)methyl)‐2‐methylpyridazin‐3(2 H )‐one ( 9a ) displayed the highest COX‐2 selectivity indices of 96, 99, and 98, respectively, and analgesic efficacies of 47%, 46%, and 45% protection, respectively. Also, compounds 4a , 8b , and 9a showed anti‐inflammatory activities of 65%, 60%, and 62% inhibition of edema, respectively, at a dose of 10 mg/kg, which is higher than that of diclofenac (58% inhibition of edema).