新型含吡唑的噻唑并[3,2-a]嘧啶类化合物的合成及其抗肿瘤活性

Synthesis and Anticancer Activities of Novel Thiazolo [3,2-a] pyrimidine Derivatives Containing Pyrazole Group

以3-甲基-1-苯基-2-吡唑啉-5-酮为原料,经Vilsmeier-Haack反应和Biginelli反应制得4-(5-氯-3-甲基-1-苯基-唑-4-基)-5-甲酸乙酯-6-甲基-3,4-二氢嘧啶-2(1H)-硫酮(3);3与芳醛经Knoevenagel反应合成了5个新型的含吡唑的噻唑[3,2-a]并嘧啶类化合物(5a^5e),其结构经1H NMR,13C NMR,IR和ESI-MS表征。采用MTT法测定了5a^5e的抗肿瘤活性。结果表明:5a^5e对人前列腺癌PC-3细胞均具有一定的体外抗增殖活性,其中2-【4-{[6-(乙氧羰酯)-5-(5-氯-3-甲基-1-苯基-吡唑-4-基)-3-氧代-7-甲基-噻唑并[3,2-a]嘧啶-2(5H)-亚基]甲基}苯氧基】乙酸(5a)活性最强,其IC50为44.45μM。

4- （ 5-Chloro-3-methyl-1 -phenyl-4-pyrazolyl ） -3,4-dihydronpyrimidin-2 （ 1H ） - （ thio ） one （3） was prepared by VilsmeierHaack and Biginelli reaction using 3-methyl-l-phenyl-2-pyrazolin-5one as the raw materials. Five novel thiazolo [ 3,2-α ] pyrimidine derivatives containing pyrazole group （Sa-Se） were synthesized by Knoevenagel reactions of 3 with arylaldehyde. The structures were characterized by ＇H NMR, 13C NMR, IR and ESI-MS. The preliminary in vitro antieancer activities of 5a - 5e against human prostate cancer PC-3 cells were tested by MTY assay. The results showed that 5a -5e exhibited certain antieancer activities and 2-[ 4- { [ 6-（ethoxyearbonyl） -5-（ 5-chloro-3- methyl-1-phenyl-4-pyrazolyl）-3-oxo-7-methyl-thiazolo [ 3,2-α ] pyrimidin-2 （ 5H ）-ylidene ] methyl } phenoxy] acetic acid（Sa） exhibited the strongest anticaneer activities with IC50 of 44.45 μM.