Receptor-based design of novel dihydrofolate reductase inhibitors: benzimidazole and indole derivatives.


Although many thousands of inhibitors of the enzyme dihydrofolate reductase (DHFR) have been synthesized, all of the very active compounds have been 2,4-diaminopyrimidines or very close analogues. This paper describes 2,4-diamino-6-benzylbenzimidazole (3b) and the corresponding indole (4), as well as more complex tri- and tetracyclic derivatives (5 and 6… (More)


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