Synthesis of new 2,3-dihydroquinazolin-4(1H)-one derivatives for analgesic and anti-inflammatory evaluation.
Starting from isatoic anhydrides, several new 2,3-dihydroquinazolin-4(1H)-one derivatives bearing chalcone or pyrazole or thiazole moieties at the third position were synthesized. The analgesic and anti-inflammatory activities for most compounds were studied at a dose level of 50 mg/kg via the acetic-acid-induced writhing-response method and carrageenan-induced edema method, respectively. The study showed that the chalcones bearing a 4-chlorophenyl group 4c or 4-nitrophenyl group 4b were the most active ones as analgesics. Both chalcone 4c and N-phenyl pyrazole bearing 4-methoxy phenyl group 5b showed a higher anti-inflammatory activity than celecoxib but still lower than that of diclofenac sodium. Moreover, the chalcone 4c has nearly the same ulcerogenic index as the selective cyclooxygenase-2 inhibitor celecoxib.
Department of Medicinal Chemistry, Faculty of Pharmacy, Zagazig University, Egypt. elsabbagh_59@yahoo.com
Osama I
OI
El-Sabbagh
Samy M
SM
Ibrahim
Mohamed M
MM
Baraka
Hend
H
Kothayer
D019342:Acetic Acid; D000700:Analgesics / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000138:chemical synthesis* / Q000494:pharmacology*; D002351:Carrageenan; D047188:Chalcones / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D010147:Pain Measurement; D011720:Pyrazoles / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology; D052999:Quinazolinones / Q000009:adverse effects* / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000139:chemically induced; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000009:adverse effects / Q000138:chemical synthesis / Q000494:pharmacology
D000700:Analgesics; D000893:Anti-Inflammatory Agents; D047188:Chalcones; D011720:Pyrazoles; D052999:Quinazolinones; D013844:Thiazoles; D002351:Carrageenan; D019342:Acetic Acid