title: New quinazolinone-pyrimidine hybrids: synthesis, anti-inflammatory, and ulcerogenicity studies.
abstract: 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 10 g (IC(50) = 116.73 μmol/kg; ulcer index = 11.38). Compound 10 g was also 2-fold more selective inhibitor of COX-2 than COX-1.
authors.affiliation: Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, 11562 Kasr El-Eini, Cairo, Egypt.
authors.forename: Safinaz E
authors.initials: SE
authors.lastname: Abbas
authors.forename: Fadi M
authors.initials: FM
authors.lastname: Awadallah
authors.forename: Nashwa A
authors.initials: NA
authors.lastname: Ibrahin
authors.forename: Eman G
authors.initials: EG
authors.lastname: Said
authors.forename: Gihan M
authors.initials: GM
authors.lastname: Kamel
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D004487:Edema / Q000188:drug therapy; D005260:Female; D008297:Male; D011743:Pyrimidines / Q000009:adverse effects* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D052999:Quinazolinones / Q000737:chemistry*; D051381:Rats; D014456:Ulcer / Q000139:chemically induced*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011743:Pyrimidines; D052999:Quinazolinones; C030986:pyrimidine