S-[2-[(2'-氨甲酰基乙基)氨基]乙基]硫代磷酸酯及相关化合物作为潜在的抗辐射剂。

S-[2-[(2'-carbamoylethyl)amino]ethyl] phosphorothioate and related compounds as potential antiradiation agents.

作者信息

Carroll F I, Gopinathan M B, Philip A

机构信息

Research Triangle Institute, Research Triangle Park, North Carolina 27709.

出版信息

J Med Chem. 1990 Sep;33(9):2501-8. doi: 10.1021/jm00171a026.

DOI:10.1021/jm00171a026

PMID:2167982

Abstract

A reinvestigation of the radiation protection activity of S-[2-[(2'-carbamylethyl)amino]ethyl] lithium hydrogen phosphorothioate (4a) revealed that this compound possessed good (70% protection at a dose of 600 mg/kg) activity. The thione and imino bioisosteres of 4, S-[2-(2'-thiocarbamylethylamino)ethyl] lithium hydrogen phosphorothioate (13a) and S-[2-(2'-amidinoethylamino)ethyl] phosphorothioic acid (18b) showed 100% protection at doses of 300 and 150 mg/kg, respectively. The N-methyl (4b) and tert-butyl (4c) analogues of amide 4a, the N-methyl (13b) analogue of the thioamide 13a, the N-methyl (18a) analogue of amidine (18b), and the cyclic amidine S-[2-[[2'-(4,5-dihydroimidozoyl)ethyl]amino]ethyl] lithium hydrogen phosphorothioate (21) all showed 80% protection at the highest dose tested.

摘要

对S-[2-[(2'-氨甲酰基乙基)氨基]乙基]硫代磷酸氢锂（4a）的辐射防护活性进行的重新研究表明，该化合物具有良好的活性（在剂量为600 mg/kg时防护率达70%）。4的硫酮和亚氨基生物电子等排体，即S-[2-(2'-硫代氨甲酰基乙基氨基)乙基]硫代磷酸氢锂（13a）和S-[2-(2'-脒基乙基氨基)乙基]硫代磷酸（18b），分别在剂量为300和150 mg/kg时显示出100%的防护率。酰胺4a的N-甲基（4b）和叔丁基（4c）类似物、硫代酰胺13a的N-甲基（13b）类似物、脒（18b）的N-甲基（18a）类似物以及环状脒S-[2-[[2'-(4,5-二氢咪唑甲酰基)乙基]氨基]乙基]硫代磷酸氢锂（21）在测试的最高剂量下均显示出80%的防护率。