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 Queener

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

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
Pages (from-to)3689-3692
Number of pages4
JournalJournal of Medicinal Chemistry
Volume47
Issue number14
DOIs
StatePublished - Jul 1 2004

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Folic Acid Antagonists
Tetrahydrofolate Dehydrogenase
Toxoplasma
Mycobacterium avium
Pyrimidines
Trimethoprim
Pathogens
Acquired Immunodeficiency Syndrome
Pyrrolo(2,3-d)pyrimidine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

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title = "Design, synthesis, and biological evaluation of 2,4-diamino-5-methyl-6- substituted-pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors",
abstract = "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.",
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T1 - Design, synthesis, and biological evaluation of 2,4-diamino-5-methyl-6- substituted-pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors

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AU - Lin, Xin

AU - Queener, Sherry

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AB - 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.

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