Synthesis and evaluation of antitubercular activity of fluorinated 5-aryl-4-(hetero)aryl substituted pyrimidines

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).…”

“…[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.…”

Recent Advances in Direct C–H Functionalization of Pyrimidines

“…This is illustrated nicely by the transformations of 5-bromopyrimidine (Scheme 36). [113][114][115][116][117][118][119][120][121] The Suzuki cross-coupling reaction can be used for modification of C5 of the pyrimidine ring, which is less activated for nucleophilic attack, while the S N H protocol is effective for nucleophilic C-H functionalization of C4. In fact, the various combinations of these two types of C-C coupling reactions, addition-oxidation S N H (AO) or addition-elimination S N H (AE), and also various sequences of steps have been used to obtain 4-(hetero)aryl-76, 5-bromo-4-(hetero)aryl-77, 5-(hetero)aryl-78, or 4,5-di(hetero)aryl-substituted pyrimidines 79 (Scheme 36).…”

Advances in Drug Discovery of New Antitubercular Multidrug-Resistant Compounds

“…Additional studies performed by this same research group have described other pyrimidine derivatives with similar antituberculosis activity. The most promising compound ( 10 ) (Figure 3) exhibited an MIC 90 value of 1.95 μM against a clinically isolated MDR-TB strain and LD 50 of 600 mg/kg in acute toxicity using mice [23]. Quinolizidine-related compounds have also been reported with antituberculosis activity in a study involving fifteen derivatives.…”