Design, Synthesis, Computational Prediction, and Biological Evaluation of Ester Soft Drugs as Inhibitors of Dihydrofolate Reductase from Pneumocystis c arinii

M Graffner-Nordberg, K Kolmodin, J Åqvist…

Index: Graffner-Nordberg; Kolmodin; Aqvist; Queener; Hallberg Journal of Medicinal Chemistry, 2001 , vol. 44, # 15 p. 2391 - 2402

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Citation Number: 87

Abstract

A series of lipophilic soft drugs structurally related to the nonclassical dihydrofolate reductase (DHFR) inhibitors trimetrexate and piritrexim have been designed, synthesized, and evaluated in DHFR assays, with special emphasis on the inhibition of P. carinii DHFR. The best inhibitors, encompassing an ester bond in the bridge connecting the two aromatic systems, were approximately 10 times less potent than trimetrexate and piritrexim. The ...