Evidence for elimination–addition mechanisms in the reactions of N-t-butyl-P-alkylphosphonamidic chlorides with t-butylamine and isopropylamine
作者:Martin J. P. Harger
DOI:10.1039/p19830002127
日期:——
ButP(Cl)NHBut obtained from ButPCl2 and t-butylamine. The phosphonamidicchlorides react with t-butylamine and isopropylamine in dichloromethane at rates that are unusually insensitive to steric effects in both the substrate and the amine; the slowest reaction [(2; R = But)+ ButNH2] is only 30 times slower than the fastest [(2; R = Me)+ PriNH2]. This is attributed to the reactions proceeding by elimination-addition
所述phosphonamidic氯化物RP(O)(CL)NHBu吨(2; R =甲基,乙基,或Pr我),可直接从相应的膦酰氯制备RP(O)Cl 2和叔丁基胺。叔丁基膦酰二氯仅在高温下才与叔丁胺反应,然后生成二酰胺Bu t P(O)(NHBu t)2作为唯一可检测的产物。但是,可以通过氧化(SO 2 Cl 2)间接制得从Bu t PCl 2获得的Bu t P(Cl)NHBu t来制备膦酰氯(2; R = Bu t)。和叔丁胺。磷酸亚氨基氯化物与叔丁胺和异丙胺在二氯甲烷中的反应速率通常对底物和胺的空间效应均不敏感。最慢的反应[(2; R =卜吨)+卜吨NH 2 ]是比最快仅慢30倍[(2; R = Me)的+ Pr的我NH 2 ]。这归因于通过消除-加成机制而不是通过对磷的亲核攻击进行的反应。在叔丁基胺和异丙胺的竞争性实验中,较少受阻胺形成的产物的形成的偏爱偏小(1.4-4.0)与反应性单体偏亚膦酸酯中间体的(部分)参与是一致的。
Combination of FBPase Inhibitors and Insulin Sensitizers for the Treatment of Diabetes
申请人:Erion D. Mark
公开号:US20080004226A1
公开(公告)日:2008-01-03
Pharmaceutical compositions containing an FBPase inhibitor and an insulin sensitizer are provided as well as methods for treating diabetes and diseases responding to increased glycemic control, an improvement in insulin sensitivity, a reduction in insulin levels, or an enhancement of insulin secretion.
Novel bisamidate phosphonate prodrugs of FBPase inhibitors of the Formula IA:
and their use in the treatment of diabetes and other conditions associated with elevated blood glucose.
Novel bisamidate phosphonate prodrugs of FBPase inhibitors of the Formula IA:及其在治疗糖尿病和其他与高血糖相关的疾病中的应用。