MECHANISM OF HYDROLYSIS OF BENZAMIDOMETHYL DERIVATIVES OF PHENOLS AND ITS IMPLICATIONS FOR PRODRUG DESIGN

被引：18

作者：

GETZ, JJ

PRANKERD, RJ

SLOAN, KB

机构：

[1] UNIV FLORIDA,DEPT MED CHEM,GAINESVILLE,FL 32610

[2] UNIV FLORIDA,DEPT PHARMACEUT,GAINESVILLE,FL 32610

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1992年 / 57卷 / 06期

关键词：

D O I：

10.1021/jo00032a020

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A series of O-benzamidomethyl derivatives of phenols was synthesized, and their rates of hydrolysis were investigated. The hydrolyses of the compounds follow pseudo-first-order kinetics resulting in quantitative and rapid regeneration of the phenol. The rates of hydrolysis were shown to be dependent on phenol nucleofugicity as well as the pK(a) of the amide. The mechanism of hydrolysis apparently involves an elimination of the phenol anion from the conjugate base of the amide (E1cB-like).

引用

页码：1702 / 1706

页数：5

共 12 条

[1] PRODRUGS FOR IMPROVED ORAL NALBUPHINE BIOAVAILABILITY - INTERSPECIES DIFFERENCES IN THE DISPOSITION OF NALBUPHINE AND ITS ACETYLSALICYLATE AND ANTHRANILATE ESTERS [J].

AUNGST, BJ ;

MYERS, MJ ;

SHEFTER, E ;

SHAMI, EG .

INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1987, 38 (1-3) :199-209

[2]

BENET LZ, 1985, PHARMACOL BASIS THER, P5

[3]

BOHME H, 1961, ARCH PHARM WEINHEIM, V294, P341

[4]

BUNDGAARD H, 1987, ACTA PHARM SUEC, V24, P233

[5]

Bunnett J. F, 1962, ANGEW CHEM INT EDIT, V1, P225, DOI DOI 10.1002/ANIE.196202251

[6]

GETZ J, UNPUB

[7] IMPROVED BUCCAL DELIVERY OF OPIOID ANALGESICS AND ANTAGONISTS WITH BITTERLESS PRODRUGS [J].

HUSSAIN, MA ;

AUNGST, BJ ;

KOVAL, CA ;

SHEFTER, E .

PHARMACEUTICAL RESEARCH, 1988, 5 (09) :615-618

[8]

JENCKS W, 1978, J AM CHEM SOC, V100, P5444

[9]

Perrin D.D., 1974, BUFFERS PH METAL ION

[10]

RICHARDSON K, 1987, MECHANISM THEORY ORG, P592

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