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.
SYNTHESIS OF BORON CHELATES FROM N-(PYRID-2-YL)- AND (N-4-METHYLPYRID-2-YL) CYANOACETAMIDES AND THEIR TAUTOMERIC TRANSFORMATIONS
Bogdanov, V. S.,Baranin, S. V.,Dib, A.,Yakovlev, I. P.,Dorokhov, V. A.
, p. 147 - 151 (1991)
Chelate complexes in which the boron atom is bound to the pyridine N atom and the O atom of the deprotonated ligand were synthesized by reaction of N-(pyrid-2-yl)- and N-(4-methylpyrid-2-yl) cyanoacetamides.A new type of intrachelate tautomeric transformation was discovered: the complexes obtained can exist in solutions in the form of two tautomers, which are derivatives of acetimidic acid or the corresponding ketene N,O-acetals.
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.
Designing, synthesis, and characterization of some novel coumarin derivatives as probable anticancer drugs
Manidhar, Darla Mark,Kesharwani, Rajesh Kumar,Reddy, N. Bakthavatchala,Reddy, C. Suresh,Misra, Krishna
, p. 4146 - 4157 (2013/09/02)
Coumarin is a naturally occurring oxygen heterocyclic having multifarious medicinal properties, hence used as a lead compound for designing new potent analogs. Based on the X-ray crystal structure of complexes of inhibitors containing coumarin nucleus with human NAD(P)H:quinone oxidoreductase-1 and human phosphodiesterase 4B enzymes, some novel coumarin derivatives have been designed as probable inhibitors specifically for pancreatic cancer. These two enzymes are overexpressed in various tumors, the former specifically in pancreatic cancer. The computational analysis by e-pharmacophore and docking studies suggested that specific groups at position 8 of 4-methyl-7- hydroxycoumarin have anticancer activity against skin cancer in mice and can enhance the anti-tumor activity. The chemical syntheses of 4-methyl-7- hydroxycoumarin and its 8-formyl derivative were carried out using Pechmann's condensation followed by Duffs reaction. Treatment of the 8-formyl derivative with nine different N,N-di substituted cyanoacetamides in the presence of piperidine afforded the corresponding nine new 8-substituted-4-methyl-7- hydroxycoumarin derivatives. These compounds were characterized by IR, 1H, 13C NMR, mass spectra and elemental analysis. Intriguingly, molecular docking suggested a remarkable binding pose for all the nine coumarin derivatives vis-a-vis coumarin itself, opening further options for designing inhibitors for tumor suppression. From the docking simulation study, it was concluded that the derived coumarin derivatives are active against more than one proteins and most importantly addition of substituents at the 8th position of 4-methyl-7-hydroxycoumarin support the possibility of new coumarin derivatives having comparatively higher binding affinity and therefore more potent inhibitors.
