Synthesis and DHFR inhibitory activity of a series of 6-substituted-2,4-diaminothieno[2,3-d]pyrimidines.
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 IC(50) values ranging from 0.24 and 11.0 microM) but those with two methylene groups between the aromatic rings were the most selective agents.
Donkor
Isaac O
IO
Department of Pharmaceutical Sciences,University of Tennessee Health Science Center, Johnson Building, Room 327E, 847 Monroe Avenue, Memphis, TN 38163, USA. idonkor@utmem.edu
Li
Hui
H
Queener
Sherry F
SF
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D009162:Mycobacterium avium / Q000201:enzymology; D045363:Pneumocystis carinii / Q000201:enzymology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*; D014122:Toxoplasma / Q000201:enzymology
D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D013762:Tetrahydrofolate Dehydrogenase