Synthesis and DHFR inhibitory activity of a series of 6-substituted-2,4-diaminothieno[2,3-d]pyrimidines

Isaac O. Donkor, Hui Li, Sherry F. Queener

Research output: Contribution to journalArticle

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Abstract

A series of 6-aralkyl substituted 2,4-diaminothieno[2,3-d]pyrimidines in which the 6-aryl group is separated from the thieno[2,3-d]pyrimidine ring by two to five methylene groups were synthesized and studied as inhibitors of dihydrofolate reductase from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and rat liver. Compounds in which the thieno[2,3-d]pyrimidine ring is separated from the 6-aryl substituent by three methylene groups were the most potent inhibitors of the series (with IC50 values ranging from 0.24 and 11.0 μM) but those with two methylene groups between the aromatic rings were the most selective agents.

Original languageEnglish (US)
Pages (from-to)605-611
Number of pages7
JournalEuropean Journal of Medicinal Chemistry
Volume38
Issue number6
DOIs
StatePublished - Jun 1 2003

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Keywords

  • DHFR
  • Diaminothieno[2,3-d]pyrimidines
  • Opportunistic infections
  • Pneumocystis carinii
  • Pneumonia

ASJC Scopus subject areas

  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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