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

Isaac O. Donkor, Hui Li, Sherry Queener

Research output: Contribution to journalArticle

42 Citations (Scopus)

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

Fingerprint

Pyrimidines
Folic Acid Antagonists
Pneumocystis carinii
Mycobacterium avium
Toxoplasma
Liver
Inhibitory Concentration 50
Rats
thieno(2,3-d)pyrimidine

Keywords

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

ASJC Scopus subject areas

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

Cite this

Synthesis and DHFR inhibitory activity of a series of 6-substituted-2,4-diaminothieno[2,3-d]pyrimidines. / Donkor, Isaac O.; Li, Hui; Queener, Sherry.

In: European Journal of Medicinal Chemistry, Vol. 38, No. 6, 01.06.2003, p. 605-611.

Research output: Contribution to journalArticle

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