New quinazolinone-pyrimidine hybrids: Synthesis, anti-inflammatory, and?ulcerogenicity studies

详细信息    查看全文

• 作者：Safinaz E. Abbas^a ; Fadi M. Awadallah^a ; ^{fadi_mae@hotmail.com} ; Nashwa A. Ibrahin^b ; Eman G. Said^b ; Gihan M. Kamel^c
• 关键词：Quinazolinone ; Pyrimidine ; Dihydropyrimidine ; Anti-inflammatory activity ; COX-1/COX-2 ; Ulcerogenicity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：July, 2012
• 年：2012
• 卷：53
• 期：Complete
• 页码：141-149
• 全文大小：507 K

文摘

Two groups of hybrid compounds: the quinazolinone-dihydropyrimidines and quinazolinone-pyrimidines, were synthesized. The starting derivative 3 was reacted with chloroacetyl chloride to give intermediate 5 which was condensed with the 2-mercaptopyrimidines 4a-c affording compounds 6a-c. These latter compounds underwent hydrolysis and N-alkylation reactions to give the dihydropyrimidine derivatives 7a-c and 8a-f, respectively. The chloro derivatives 9a-c subsequently reacted with various anilines furnishing compounds 10a-i. The anti-inflammatory activity of the synthesized compounds were evaluated using the carrageenan-induced rat paw oedema model and ulcer indices for the most active compounds were calculated. Five compounds were found more active and less ulcerogenic than diclofenac particularly compound 10g (IC₅₀ = 116.73 ¦Ìmol/kg; ulcer index = 11.38). Compound 10g was also 2-fold more selective inhibitor of COX-2 than COX-1.