Journal of Pharmaceutical Sciences p. 36 - 43 (1986)
Update date:2022-08-05
Topics:
Bundgaard
Falch
Larsen
Mikkelson
Various alkyl and aralkyl esters of pilocarpic acid were synthesized and evaluated as prodrug forms for pilocarpine with the purpose of improving the ocular bioavailability of pilocarpine through increased corneal membrane permeability. The esters were found to undergo a quantitative cyclization to pilocarpine in aqueous solution of pH 3.5-10, the rate of cyclization being a function of the polar and steric effects within the alcohol portion of the esters. The rates of lactonization increased proportionally with the hydroxide ion activity over the pH range studied which is in accord with a reaction mechanism involving intramolecular nucleophilic attack of alkoxide ion on the ester carbonyl moiety. At pH 7.4 and 37° C, half-times of lactonization ranging from 30 min (p-chlorobenzyl ester) to 1105 min (n-hexyl ester) were observed for the various esters. The esters are markedly more lipophilic than pilocarpine. The results suggested that the pilocarpic acid esters may be potentially useful prodrugs, especially when further derivatized to give in vitro stable pilocarpic acid diesters.
View MoreContact:18710867521(wechat)
Address:Rm10516,Galaxy Tech Building #2,No.25 Tangyan Rd,Hi-Tech Zone,Xi'an, China
Contact:021
Address:Pudong
Contact:+1-416-493-6870
Address:Toronto, Canada
Hubei Xinjing New Material Co.,Ltd
Contact:+86-27-83313147
Address:Room402.#Bthe 7th,Headquarter of Huifeng Corporation Qiaokou District,Wuhan China
Tangshan Moneide Trading Co., Ltd.
Contact:+86-315-8309571
Address:2-7-420 Jidong Building Materials Commercial Center, Tangshan, Hebei, 064000 China
Doi:10.1021/ja01061a026
(1964)Doi:10.1021/jo01044a022
(1963)Doi:10.1134/S1070427209020293
(2009)Doi:10.1021/jo062173y
(2007)Doi:10.1002/ejoc.200600354
(2007)Doi:10.1021/ol503291s
(2015)