132371-14-3Relevant articles and documents
SYNTHESIS OF N-(2-PYRIDYL)CYANOACETAMIDES AND 4-AMINO-2H-PYRIDOPYRIMIDIN-2-ONES FROM ETHYL CYANOACETATE AND 2-AMINOPYRIDINE
Dorokhov, V. A.,Baranin, S. V.,Dib, A.,Bogdanov, V. S.,Yakovlev, I. P.,et al.
, p. 1918 - 1923 (1990)
The reaction of 2-aminopyridine and 2-aminopicolines with ethyl cyanoacetate under high pressures results in the formation of 4-amino-4H-pyridopyrimidin-2-ones.Depending on the structure of the initial pyridine base, heating of a mixture of the above reagents under low vacuum gives either the same products or their isomeric N-(2-pyridyl)cyanoacetamides.The mutual transformations of the synthesized isomers were studied; it was found that cyanoacetamides are readily cyclized by the action of alcoholic solution of HCl into pyridopyrimidin-2-ones, while the latter, during sublimation or heating in DMSO, undergo opening of the pyrimidine ring.
Discovery of Novel Thiophene-arylamide Derivatives as DprE1 Inhibitors with Potent Antimycobacterial Activities
Wang, Pengxu,Batt, Sarah M.,Wang, Bin,Fu, Lei,Qin, Rongfei,Lu, Yu,Li, Gang,Besra, Gurdyal S.,Huang, Haihong
, p. 6241 - 6261 (2021/05/06)
In this study, we report the design and synthesis of a series of novel thiophene-arylamide compounds derived from the noncovalent decaprenylphosphoryl-β-d-ribose 2′-epimerase (DprE1) inhibitor TCA1 through a structure-based scaffold hopping strategy. Systematic optimization of the two side chains flanking the thiophene core led to new lead compounds bearing a thiophene-arylamide scaffold with potent antimycobacterial activity and low cytotoxicity. Compounds 23j, 24f, 25a, and 25b exhibited potent in vitro activity against both drug-susceptible (minimum inhibitory concentration (MIC) = 0.02-0.12 μg/mL) and drug-resistant (MIC = 0.031-0.24 μg/mL) tuberculosis strains while retaining potent DprE1 inhibition (half maximal inhibitory concentration (IC50) = 0.2-0.9 μg/mL) and good intracellular antimycobacterial activity. In addition, these compounds showed good hepatocyte stability and low inhibition of the human ether-à-go-go related gene (hERG) channel. The representative compound 25a with acceptable pharmacokinetic property demonstrated significant bactericidal activity in an acute mouse model of tuberculosis. Moreover, the molecular docking study of template compound 23j provides new insight into the discovery of novel antitubercular agents targeting DprE1.
