Synthesis and Biological Evaluation of New Dipyridylpteridines, Lumazines, and Related Analogues

Abstract

Condensation of 4,5‐diaminopyrimidines 2 and 3 with 2,2ʹ‐dipyridil (4) afforded 6,7‐bis(2‐pyridyl)pteridine‐2‐one analogues 5 and 7, respectively. Analogously, 6,7‐bis(2‐pyridyl)luamzine derivatives 13, 15, 17, and 23 were synthesized from reaction of 5,6‐diamino‐2‐thiopyrimidines 13, 14, and 22 with 4, respectively, while condensation of 4,5,6‐triaminopyrimidines (25) or 5,6‐diamino analogue 26 with 4 furnished the 4‐amino‐pteridine analogue 27 and 28, respectively. Thiation of the new pteridines and lumazines afforded the 4‐thio analogues 6, 8, 16, and 24. Treatment of 6 and 8 with methanolic ammonia afforded the 4‐isopterine analogues 9 and 10, respectively. Alkylation of 15 with substituted phenacyl chloride furnished 18 and 19, which cyclized to the thiazolo‐pteridine derivatives 20 and 21, respectively, on treatment with polyphosphoric acid. Alternatively, 27 was prepared from treatment of 24 with methanolic ammonia under drastic conditions. Condensation of 2 or 29 with 2‐oxo‐2‐(thiophen‐2‐yl)acetaldehyde oxime (11) gave the 6‐(2‐thienyl)‐pteridine‐4‐one (12) and 5‐chloro‐2‐(2‐thienyl)pyrido[3,4‐b]pyrazine (31), respectively. All compounds were evaluated for their antiviral activity against the replication of HIV‐1 and HIV‐2 in MT‐4. Some of the synthesized compounds were tested against the bacterial species, Escherichia coli and Staphylococcus aureus, as well as fungal species, Candida tropicalis and Candida albicans.