Habib N S, Soliman R, Ismail K, Hassan A M, Sarg M T
Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt.
Boll Chim Farm. 2003 Nov;142(9):396-405.
Five main classes of novel pyrimidine derivatives have been synthesized; namely 6-substituted phenyl-5-cyano-3-methyl-2-phenacylhydrazino-3,4-dihydropyrimidin-4-ones 4a-e; 6-substituted phenyl-2-arylidene hydra-zino-5-cyano-3-methyl-3,4-dihydropyrimidin-4-ones 5a-i; 6-substituted phenyl-2-acylhydrazino-5-cyano-3-methyl-3,4-dihydropyrimidin-4-ones 7a-d, 8a-e and 9a-c; three novel series of 1,2,4-triazolo[4,3-a] pyrimidones 10a,b, 11a-d and 12a-d and 6-substituted phenyl-7-cyano-9-methyl-3-phenyl or 4-chlorophenyl-4,9-dihydropyrimido[2,1-c][1,2,4] triazin-8-ones 13a-c. Besides, the azide compound 2-azido-5-cyano-3-methyl-6-phenyl-3,4-dihydropyrimidin-4-one 6 was also synthesized. The prepared compounds were tested for antimicrobial and anticancer activity. Compounds 4b and 4d showed promising activity against Escherichia coli. Compounds 3c, 5c, 5e, 5g and 7b were active in the three cell line antitumor one dose primary assay and were evaluated in the 60 human tumor full panel cell line invitro screening. Compound 5c showed promising activity against all types of leukemia especially leukemia K-562 and leukemia SR with GI50 = 1.61 and 2.63 mmol/l respectively.
已合成了五类新型嘧啶衍生物；即6-取代苯基-5-氰基-3-甲基-2-苯甲酰肼基-3,4-二氢嘧啶-4-酮4a-e；6-取代苯基-2-亚芳基肼基-5-氰基-3-甲基-3,4-二氢嘧啶-4-酮5a-i；6-取代苯基-2-酰肼基-5-氰基-3-甲基-3,4-二氢嘧啶-4-酮7a-d、8a-e和9a-c；三个新型系列的1,2,4-三唑并[4,3-a]嘧啶酮10a、b，11a-d和12a-d以及6-取代苯基-7-氰基-9-甲基-3-苯基或4-氯苯基-4,9-二氢嘧啶并[2,1-c][1,2,4]三嗪-8-酮13a-c。此外，还合成了叠氮化合物2-叠氮基-5-氰基-3-甲基-6-苯基-3,4-二氢嘧啶-4-酮6。对所制备的化合物进行了抗菌和抗癌活性测试。化合物4b和4d对大肠杆菌显示出有前景的活性。化合物3c、5c、5e、5g和7b在三细胞系抗肿瘤单剂量初筛试验中具有活性，并在60种人类肿瘤全板细胞系体外筛选中进行了评估。化合物5c对所有类型的白血病尤其是白血病K-562和白血病SR显示出有前景的活性，其GI50分别为1.61和2.63 mmol/L。
