Structural Studies on Bioactive Compounds. 34. 1 Design, Synthesis, and Biological Evaluation of Triazenyl-Substituted Pyrimethamine Inhibitors of Pneumocystis …

DCM Chan, CA Laughton, SF Queener…

Index: Chan; Laughton; Queener; Stevens Journal of Medicinal Chemistry, 2001 , vol. 44, # 16 p. 2555 - 2564

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Citation Number: 21

Abstract

The triazenyl-pyrimethamine derivative 3a (TAB), a potent and selective inhibitor of Pneumocystis carinii DHFR, was selected as the starting point for a lead optimization study. Molecular modeling studies, corroborated by a recent crystal structure determination of the ternary complex of P. carinii DHFR-NADPH bound to TAB, predicted that modifications to the acetoxy residue of the lead inhibitor could exploit binding opportunities in the vicinity of an ...