Design, synthesis, and biological evaluation of 2,4-diamino-5-methyl-6- substituted-pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors

Aleem Gangjee, Xin Lin, Sherry F. Queener

Research output: Contribution to journalArticle

36 Scopus citations


2,4-Diamino-5-methyl-6-(substituted-phenyl)thiopyrrolo[2,3-d]pyrimidines 4-11 were synthesized as dihydrofolate reductase (DHFR) inhibitors against opportunistic pathogens that afflict patients with AIDS. Synthesis was achieved from 2,4-diamino-5-methypyrrolo[2,3-d]pyrimidine and substituted phenylthiols under modified conditions reported by Gangiee et al. Some of these compounds were potent and selective against DHFR from both Toxoplasma gondii and Mycobacterium avium compared to mammalian DHFR. Compound 11 with a 1-naphthyl substituent is 16-fold more potent and equally selective against Toxoplasma gondii DHFR as the clinically used trimethoprim.

Original languageEnglish (US)
Pages (from-to)3689-3692
Number of pages4
JournalJournal of Medicinal Chemistry
Issue number14
StatePublished - Jul 1 2004


ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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