Novel 2-amino-4-oxo-5-arylthio-substituted-pyrrolo[2,3-d]pyrimidines as nonclassical antifolate inhibitors of thymidylate synthase.
Novel 2-amino-4-oxo-5-arylthio-substituted-pyrrolo[2,3-d]pyrimidines as nonclassical antifolate inhibitors of thymidylate synthase.
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新型 2-氨基-4-氧代-5-芳硫基取代-吡咯并[2,3-d]嘧啶作为胸苷酸合成酶的非经典抗叶酸抑制剂。
DOI：
10.1016/j.bmcl.2005.03.029
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Kisliuk,RoyL
中科院分区：
文献类型：
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作者：
Gangjee,Aleem;Jain,HiteshkumarD;Kisliuk,RoyL
合成了17个新型的2-氨基-4-氧-5-[（取代苯基）硫]吡咯[2,3-d]嘧啶，作为胸苷酸合成酶（TS）的潜在抑制剂和抗肿瘤药物。这些类似物在侧链的苯基环上含有多种吸电子取代基，并被评价为人类TS （hTS）和大肠杆菌TS以及人类和大肠杆菌二氢叶酸还原酶（DHFR）的抑制剂。其中，类似物14、17和18对hTS具有较强的抑制作用，ic50值分别为0.28、0.21和0.22μM，比临床使用的ZD1694、2和LY231514、3对人TS的抑制作用更强。
A series of 17 novel 2-amino-4-oxo-5-[(substituted phenyl)thio]pyrrolo[2,3-d]pyrimidines were synthesized as potential inhibitors of thymidylate synthase (TS) and as antitumor agents. The analogues contain a variety of electron withdrawing substituents on the phenyl ring of the side chain and were evaluated as inhibitors of human TS (hTS) and Escherichia coli TS and of human and E. coli dihydrofolate reductase (DHFR). The analogues 14, 17, and 18 were potent inhibitors of hTS with IC50values of 0.28, 0.21, and 0.22μM, respectively, and were more potent than the clinically used ZD1694, 2 and LY231514, 3 against human TS.