Novel 2-amino-4-oxo-5-arylthio-substituted-pyrrolo[2,3-d]pyrimidines as nonclassical antifolate inhibitors of thymidylate synthase

被引：25

作者：

Gangjee, A ^{[1
]}

Jain, HD

Kisliuk, RL

机构：

[1] Duquesne Univ, Grad Sch Pharmaceut Sci, Div Med Chem, Pittsburgh, PA 15282 USA

[2] Tufts Univ, Sch Med, Dept Biochem, Boston, MA 02111 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 09期

关键词：

D O I：

10.1016/j.bmcl.2005.03.029

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

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 IC50 values of 0.28, 0.21, and 0.22 mu M, respectively, and were more potent than the clinically used ZD1694, 2 and LY231514, 3 against human TS. (c) 2005 Elsevier Ltd. All rights reserved.

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页码：2225 / 2230

页数：6

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