Synthesis of three carbon atom bridged 2,4-diaminopyrrolo[2,3-d]- pyrimidines as nonclassical dihydrofolate reductase inhibitors

Aleem Gangjee, Zhengqu Ye, Sherry Queener

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

A series of seven nonclassical three carbon atom bridged 2,4-diamino-5-substituted-pyrrolo[2,3-d]-pyrimidines 1a-g were synthesized as potential inhibitors of dihydrofolate reductase. Selective oxidation of diols 7a-g affords oe-hydroxy ketones 8a-g. Subsequent condensation with malononitrile gave the requisite 2-amino-3-cyano-4-substituted furan precursors 9a-g. Cyclocondensation with guanidine in refluxing ethanol in one step affords the three carbon atom bridged 2,4-diamino-5-substituted-pyrrolo[2,3-d]-pyrimidines 1a-g. Preliminary biological results indicated that these compounds showed moderate inhibitory activities against dihydrofolate reductases from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium and rat liver with IC50 values in the 0.66 μM - 70.1 μM range and some compounds had marginal selectivity for T. gondii dihydrofolate reductase.

Original languageEnglish
Pages (from-to)1127-1133
Number of pages7
JournalJournal of Heterocyclic Chemistry
Volume42
Issue number6
StatePublished - Sep 2005

Fingerprint

Folic Acid Antagonists
Pyrimidines
Tetrahydrofolate Dehydrogenase
Carbon
Atoms
Guanidine
Ketones
Liver
Rats
Condensation
Ethanol
Oxidation
Pyrrolo(2,3-d)pyrimidine
furan
dicyanmethane

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Synthesis of three carbon atom bridged 2,4-diaminopyrrolo[2,3-d]- pyrimidines as nonclassical dihydrofolate reductase inhibitors. / Gangjee, Aleem; Ye, Zhengqu; Queener, Sherry.

In: Journal of Heterocyclic Chemistry, Vol. 42, No. 6, 09.2005, p. 1127-1133.

Research output: Contribution to journalArticle

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AB - A series of seven nonclassical three carbon atom bridged 2,4-diamino-5-substituted-pyrrolo[2,3-d]-pyrimidines 1a-g were synthesized as potential inhibitors of dihydrofolate reductase. Selective oxidation of diols 7a-g affords oe-hydroxy ketones 8a-g. Subsequent condensation with malononitrile gave the requisite 2-amino-3-cyano-4-substituted furan precursors 9a-g. Cyclocondensation with guanidine in refluxing ethanol in one step affords the three carbon atom bridged 2,4-diamino-5-substituted-pyrrolo[2,3-d]-pyrimidines 1a-g. Preliminary biological results indicated that these compounds showed moderate inhibitory activities against dihydrofolate reductases from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium and rat liver with IC50 values in the 0.66 μM - 70.1 μM range and some compounds had marginal selectivity for T. gondii dihydrofolate reductase.

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