Fluorinated 1,2,4-Triazolo[1,5-a]pyrimidine-6-carboxylic acid derivatives as antimycobacterial agents.
A series of fluorinated 1,2,4-triazolo[1,5-a]pyrimidine-6-carboxylic acid derivatives was designed and synthesized as fluoroquinolone analogues. The synthesized compounds were screened against Mycobacterium tuberculosis H(37)R(v) strain at 6.25 microg/mL concentration. Compound 4, the 7-oxo-2-(trifluoromethyl)-4,7-dihydro-1,2,4-triazolo[5,1-a]pyrimidine-6-carboxylic acid was found to be a very potent inhibitor, being able to inhibit 92% growth of M. tuberculosis H(37)R(v )at 6.25 microg/mL concentration. At the same time, it proofed to be nontoxic to mammalian cells (IC(50) > 62.5 microg/mL in VERO cells).
Abdel-Rahman
Hamdy M
HM
Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt. hamdym@aun.edu.eg
El-Koussi
Nawal A
NA
Hassan
Hoda Y
HY
D000818:Animals; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D024841:Fluoroquinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D014709:Vero Cells
C539951:7-oxo-2-(trifluoromethyl)-4,7-dihydro-1,2,4-triazolo(5,1-a)pyrimidine-6-carboxylic acid; D000995:Antitubercular Agents; D024841:Fluoroquinolones; D011743:Pyrimidines; D014230:Triazoles