Journal of Pharmaceutical Sciences p. 285 - 298 (1988)
Update date:2022-07-29
Topics:
Nielsen
Bundgaard
Benzoic acid esters of various substituted 2-hydroxyacetamides (glycolamides) were found to be hydrolyzed extremely rapidly in human plasma solutions, the half-lives of hydrolysis being less than 5 s in 50% plasma solutions for some N,N-disubstituted glycolamide esters. The rapid rate of hydrolysis could be largely attributed to cholinesterase (also called pseudocholinesterase) present in plasma. From a study of a variety of substituted glycolamide esters and structurally related esters, the most prominent structural requirement needed for a rapid rate of hydrolysis was found to be the glycolamide ester structure combined with the presence of two substituents on the amide nitrogen atom. A structural similarity of such esters with benzoylcholine, a good substrate for cholinesterase, was put forward. Esters of N,N-disubstituted glycolamides are suggested to be a useful biolabile prodrug type for several carboxylic acid agents. The esters combine a high susceptibility to undergo enzymatic hydrolysis in plasma with a high stability in aqueous solution. Furthermore, as demonstrated with the benzoic acid model esters, it is feasible to obtain ester derivatives with almost any desired water solubility or lipophilicity with retainment of marked lability to enzymatic hydrolysis.
View MoreWuxi Zuping Food Science And Technology Co.,LTD.
Contact:+86-510-87210822
Address:Guanlin town
FOSHAN NANHAI ZHONGNAN PHARMACEUTICAL FACTORY
Contact:0086-0757-85609331
Address:XIAHENGTIAN INDUSTRIAL ZONE,SHAYONG VILLAGE,LISHUI TOWN
Contact:86-21-57725962
Address:shanghai
Liaoyang hengye Chemical Co., Ltd.
Contact:86-419-5850866
Address:North Old Xiaoxiao Road,Yantai District, Dengta, Liaoyang, Liaoning, China
Longhui qunfeng Chemical Co., Ltd
Contact:86-731-82173407
Address:South-east Industrial Park, Longhui County, Hunan Province, China
Doi:10.1021/acs.orglett.5b01602
(2015)Doi:10.1107/S0108270102010375
(2002)Doi:10.1021/jo00906a026
(1975)Doi:10.3109/00498259409043246
(1994)Doi:10.1021/jo00871a044
(1976)Doi:10.1002/hlca.19750580841
(1975)