57160-46-0Relevant articles and documents
Pd-Catalyzed Carbonylation of Acyl Azides
Chang, Wenxu,Fu, Bin,Huang, Baoliang,Jiao, Lei,Li, Zongyang,Wang, Peng,Xu, Shiyang,Yuan, Chenhui,Zhang, Zhenhua
, p. 9497 - 9508 (2019/08/26)
Pd-catalyzed reactions of azides with CO to access an isocynate intermediate have been developed extensively in recent years. However, the catalytic carbonylation of sensitive acyl azides has not been reported. Herein, we report a simple Pd-catalyzed carbonylation reaction of acyl azides with broad substrate scope, high efficiency, and simple operation under mild conditions, which provides facile access to acyl ureas. In addition, a mechanistic study was carried out by both experiment and DFT calculation. Control experiments and kinetic study revealed that the real active palladium species were Pd(0). The result of kinetic study suggested that palladium catalyst, azide, and CO were all involved in the turnover-limiting step except for amine. Further DFT study suggested that an unprecedented five-membered palladacycle intermediate was the key intermediate in the carbonylation reaction. ?
Novel agents effective against solid tumors: The diarylsulfonylureas. Synthesis, activities, and analysis of quantitative structure-activity relationships
Howbert,Grossman,Crowell,Rieder,Harper,Kramer,Tao,Aikins,Poore,Rinzel,Grindey,Shaw,Todd
, p. 2393 - 2407 (2007/10/02)
A series of diarylsulfonylureas with exceptionally broad-spectrum activity against syngeneic rodent solid tumors in vivo is described. Their discovery resulted from a program dedicated to in vivo screening for novel oncolytics in solid tumor models, rather than traditional ascites leukemia models. The structures, oral efficacy, side-effect profile, and mechanism of action of these sulfonylureas appear to be distinct from previously known classes of oncolytics. An extensive series of analogues was prepared to probe structure-activity relationships (SAR), with particular focus on the substituent patterns of each aryl domain. Quantitative analysis of these substituent SARs, using the method of cluster significance analysis, showed the lipophilicity of the substituents to be the dominant determinant of activity. One compound from the series, LY186641 (104, sulofenur), has progressed to Phase I clinical trials as an antitumor drug.
KINETICS AND MECHANISM OF METHANOLYSIS OF BENZOYL DERIVATIVES OF SUBSTITUTED PHENYLUREAS AND PHENYLTHIOUREAS
Kavalek, Jaromir,El Bahaie, Said,Sterba, Vojeslav
, p. 2103 - 2110 (2007/10/02)
The methanolysis rate constants and dissociation constants have been measured of benzoyl derivatives of substituted phenylureas and phenylthioureas.The dissociation constants of the thio derivatives are higher by 1 order of magnitude and the rate constants are higher by 2 orders of magnitude than the respective values of the oxygen analogues.Logarithms of the rate and dissociation constants have been correlated with Hammett ? constant; the ρ constant of the methanolysis of the oxygen derivatives is almost 2 * higher than that of the thio derivatives, which is explained by a change in the rate-limiting step.Methylation of the phenyl nitrogen atom increases the acidity by almost 2 orders of magnitude.This effect is due obviously to steric hindrance to the conjugation with the adjacent carbonyl or thiocarbonyl group.
