Design, syntheses and evaluation of 4-oxo-5-cyano thiouracils as SecA inhibitors

Microwave-assisted synthesis and evaluation of antibacterial activity of novel 6-fluoroaryl-[1,2,4]triazolo[1,5-a]pyrimidines

“…[20][21][22][23][24][25] We have exploited this protocol for the synthesis of 6-phenyl-(5a) and 6-(fluoroaryl)- [1,2,4]triazolo [1,5-a]pyrimidines (5b-j). Indeed, compounds 5a-f were obtained in good yields by reacting the readily-available 6-bromo- [1,2,4]triazolo [1,5-a]pyrimidine (3) with phenylboronic (4a) and various fluorinated phenylboronic acids (4b-j) under microwave irradiation, using 1,4-dioxane-H2O (4:3) as solvent, and K2CO3 and Pd(PPh3)4, as catalyst (Scheme 2, Table 1). Figure 1.…”

“…The antibacterial assay data show that the investigated [1,2,4]triazolo[1,5-a]pyrimidines showed moderate activity against Mycobacterium tuberculosis H37Rv in vitro. Displacement of the bromo atom of the pyrimidine ring with a fluoroaryl substituent leads to a reduction in antimycobacterial activity.…”

“…[15][16][17][18][19] We have recently elucidated how a fluorine atom (or CF3-group), incorporating at various positions a 5-(fluoroaryl) substituent in 4-(hetero)arylpyrimidines can affect their antibacterial activity against Mycobacterium tuberculosis and other pathogenic strains such as M. avium and M. terrae. 20 In this communication we report the synthesis of novel 6-fluoroaryl substituted [1,2,4]triazolo [1,5-a]pyrimidines using microwave-assisted Suzuki cross-coupling, and present data on their antimicrobial activities in vitro against Mycobacterium tuberculosis H37Rv and the gram-negative Neisseria gonorrhoeae ATCC 49226 bacteria.…”

SecA: A Potential Antimicrobial Target

“…Compound 8c (Table 4) shows ion-channel inhibition with IC 50 of 2.5 μM and several fold enhanced antimicrobial potency with MIC ~ 1 μM against (leaky mutant) E. coli NR698, as compared with RB. SAR studies on 20 analogs revealed that the xanthene ring on RB is essential for inhibition; the chlorinated benzoate position ( 8a , Table 4) can tolerate fairly substantial modifications; and the carboxylate group and the aryl ring are not required for activity [151,152]. …”

Synthesis and Biological Value of Thiouracils and Fused Thiouracils (A review)

“…Moreover, compound 105 was found to be broad spectrum antimicrobial agent 44 and it also exhibit promising antifungal activity against C.albicans. 4-Oxo-5-cyano thiouracils 116 showed good antimicrobial activity 57 against Escherichia coli mutant strain, NR698 and evaluated as SecA inhibitors. Protein translocation is essential for bacterial survival and the most important translocation mechanism is the secretion (Sec) pathway in which Sec A is a central core driving force.…”