Design, Synthesis, and Biological Activities of Classical N-{4-[2-(2-Amino-4-ethylpyrrolo [2, 3-d] pyrimidin-5-yl) ethyl] benzoyl}-l-glutamic Acid and Its 6-Methyl …

A Gangjee, J Yu, RL Kisliuk, WH Haile…

Index: Gangjee, Aleem; Yu, Jianming; Kisliuk, Roy L.; Haile, William H.; Sobrero, Giulia; McGuire, John J. Journal of Medicinal Chemistry, 2003 , vol. 46, # 4 p. 591 - 600

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Citation Number: 48

Abstract

Two novel analogues, N-{2-amino-4-ethyl [(pyrrolo [2, 3-d] pyrimidin-5-yl) ethyl] benzoyl}-l- glutamic acid (2) and N-{2-amino-4-ethyl-6-methyl [(pyrrolo [2, 3-d] pyrimidin-5-yl) ethyl] benzoyl}-l-glutamic acid (4), were designed and synthesized as potent dual inhibitors of thymidylate synthase (TS) and dihydrofolate reductase (DHFR) and as antitumor agents. Compound 2 had inhibitory potency against human DHFR similar to N-{4-[2-(amino-3, 4- ...