126532-05-6Relevant articles and documents
Strengthening N...X halogen bonding via nitrogen substitution in the aromatic framework of halogen-substituted arylpyrazinamides
Khavasi, Hamid Reza,Hosseini, Mahdieh,Tehrani, Alireza Azhdari,Naderi, Soheila
, p. 4546 - 4553 (2014)
The importance of N...X halogen bonding in a series of N-(5-halo-2-pyridinyl)pyrazine-2-carboxamides has been investigated by different methods. The results show that when nitrogen is substituted for carbon in the aryl backbone of the parent compound, it can affect the electron accepting ability of bromine and iodine substituents. Thus, a stronger halogen bond can be formed. This journal is the Partner Organisations 2014.
Synthesis of pyrazinamide analogues and their antitubercular bioactivity
Wati, First A.,Adyarini, Prisna U.,Fatmawati, Sri,Santoso, Mardi
, p. 2157 - 2163 (2020/10/02)
The Yamaguchi reaction is widely and generally applied to synthesize esters and lactones. It involves 2,4,6-trichlorobenzoyl chloride as the Yamaguchi reagent, 4-dimethylaminopyridine, and triethylamine. Pyrazinamide is a crucial first-line drug for tuberculosis treatment, therefore their analogues are interesting in organic synthesis. In general, the synthesis pyrazinamide analogues involve reaction of pyrazine-2-carboxylic acids with thionyl chloride to yield the corresponding acyl chlorides, which on treatment with amines gave pyrazine-2-carboxamides. However, thionyl chloride is listed under the Chemical Weapons Convention and releases toxic sulfur oxide when react with carboxylic acid. We successfully synthesized series of pyrazinamide analogues using the Yamaguchi reaction. The synthesis involved reaction of pyrazine-2-carboxylic acid with various aliphatic and aromatic amines in the presence of Yamaguchi reagent and 4-dimethylaminopyridine. The yield of the pyrazine-2-carboxamides and the reaction time depended on the type of the amine (aliphatic vs aromatic), substitution pattern, and number of substituents on the aromatic amines. N-(4-chlorophenyl)pyrazine-2-carboxamides can be prepared by this method in 81% yield; N-(2-ethylhexyl)pyrazine-2-carboxamide and N-(4-fluorobenzyl)pyrazine-2-carboxamide showed the best activity against Mycobacterium tuberculosis H37Rv (6.25 μg/mL). This result could lead to find more active pyrazinamide analogues.
Synthesis and antitubercular evaluation of N-Arylpyrazine and N,Na-Alkyl-diylpyrazine-2-carboxamide derivatives
Bispo, Marcelle De Lima Ferreira,Goncalves, Raoni Schroeder Borges,Lima, Camilo Henrique Da Silva,Cardoso, Laura Nogueira De Faria,Lourenco, Maria Cristina Silva,De Souza, Marcus Vinicius Nora
, p. 1317 - 1322 (2013/02/22)
Two series of pyrazinamide (PZA) derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. Some compounds exhibited minimum inhibitory concentration activity of 50-100 μg/mL, greater than the first line antituberculosis drug PZA in Alamar Blue assay (>100 μg/mL). The obtained activities can be considered promising results, which characterizes these compounds as good start points to development of new antitubercular agents.
