CHEMICAL AND PLASMA HYDROLYZES OF A DIPHENYL ALPHA-AMINOMETHYL PHOSPHONATE PRODRUG INHIBITOR OF NEUTRAL ENDOPEPTIDASE-24.11

被引：7

作者：

DELOMBAERT, S

SINGH, K

BLANCHARD, L

SOLIMAN, VF

机构：

[1] Research Department, Pharmaceuticals Division, CIBA-GEIGY Corporation, Summit

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1994年 / 4卷 / 07期

关键词：

D O I：

10.1016/S0960-894X(01)80259-6

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The rate and product selectivity of the hydrolysis of CGS 25462 (1), an orally active diphenyl phosphonate prodrug of a potent neutral endopeptidase 24.11 inhibitor, has been studied in acidic and basic solutions and in the plasma of four species. While the chemical hydrolysis of 1 generally afforded the monophenyl phosphonate intermediate 2, further conversion to the bioactive phosphonic acid 3 occurred in bicarbonate solution. Concerning the generation of 3 from a in plasma, the data are consistent with the involvement of a biological catalysis, which may also apply in the hydrolysis of the prodrug in vivo.

引用

页码：899 / 902

页数：4

共 16 条

[1]

BECKER ELMER L., 1964, BIOCHEM PHARMACOL, V13, P1219, DOI 10.1016/0006-2952(64)90123-6

[2] REACTIONS OF PHOSPHONIC ACID ESTERS WITH NUCLEOPHILES .1. HYDROLYSIS [J].