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.

Therapeutic potential of pteridine derivatives: A comprehensive review

“…Dipyridylpteridine derivatives were active against HIV‐1 (strain III B ) cultured in human T‐lymphocyte (MT‐4) cells. Compounds 58 and 59 achieved IC 50 values >3.23 and >2.11 μM, respectively, while their CC 50 were 10.52 and 18.99 μM for each compound …”

“…The antimicrobial properties of a series of dipyridylpteridine derivatives were evaluated by Abbas et al, showing antiviral, antibacterial, and antifungal potential (see below). Among the tested compounds, compound 53 (4‐amino‐6,7‐bis(2‐pyridyl)‐pteridin‐2‐one) showed the highest antibacterial potential, as it produced an inhibition zone of 29 mm against E. coli (ATCC 25922).…”

“…The antifungal activities of pteridine‐based compounds have been scarcely studied. Some compounds from the already mentioned dipyridylpteridine series have also shown antifungal properties; thus, compound 62 reached diameter of inhibition zone values over 33 mm against C. albicans and C. tropicalis (Table ) …”

Bicyclic 6-6 Systems: Pteridines

“…Introduction of amino functionality at C-4 on the pyrimidine ring is possible by treatment with methanolic ammonia, which resulted in formation of isopterin analogues 70 and 71 in moderate yield. 50…”