Design and synthesis of novel 6, 7-imidazotetrahydroquinoline inhibitors of thymidylate synthase using iterative protein crystal structure analysis

SH Reich, MAM Fuhry, D Nguyen, MJ Pino…

Index: Reich, Siegfried H.; Fuhry, Mary Ann M.; Nguyen, Dzuy; Pino, Mark J.; Welsh, Katherine M.; et al. Journal of Medicinal Chemistry, 1992 , vol. 35, # 5 p. 847 - 858

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Citation Number: 53

Abstract

Antifolate inhibitors of thymidylate synthase (TS) have primarily been based on the structure of folic acid. This paper describes the identification and development of novel 6, 7- imidazotetrahydrcquinoline TS inhibitors by iterative ligand design, synthesis, and crystallographic analysis of protein-inhibitor complexes. Beginning with a high-resolution crystal structure of E. coli TS (TS, EC 2.1. 1.451, an imidazotetrahydroquinoline inhibitor ...