Design, synthesis, and antifolate activity of new analogues of piritrexim and other diaminopyrimidine dihydrofolate reductase inhibitors with ω-carboxyalkoxy or ω- …

…, RA Forsch, SF Queener, A Rosowsky

Index: Chan, David C. M.; Fu, Hongning; Forsch, Ronald A.; Queener, Sherry F.; Rosowsky, Andre Journal of Medicinal Chemistry, 2005 , vol. 48, # 13 p. 4420 - 4431

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Citation Number: 49

Abstract

As part of a search for dihydrofolate reductase (DHFR) inhibitors combining the high potency of piritrexim (PTX) with the high antiparasitic vs mammalian selectivity of trimethoprim (TMP), the heretofore undescribed 2, 4-diamino-6-(2', 5'-disubstituted benzyl) pyrido [2, 3-d] pyrimidines 6-14 with O-(ω-carboxyalkyl) or ω-carboxy-1-alkynyl groups on the benzyl moiety were synthesized and tested against Pneumocystis carinii, Toxoplasma gondii, ...