synthesis, ex vivo and in vitro hydrolysis study of an indoline derivative designed as an anti-inflammatory with reduced gastric ulceration properties合成、体外体外水解研究二氢吲哚衍生物的设计为抗炎与减少胃溃疡属性.pdf

Molecules 2009, 14, 3187-3197; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Communication Synthesis, ex Vivo and in Vitro Hydrolysis Study of an Indoline Derivative Designed as an Anti-Inflammatory with Reduced Gastric Ulceration Properties Man Chin Chung 1,*, Jean Leandro dos Santos 1, Ednir Vizioli Oliveira 1, Lorena Blau 1, 1 2 Renato Farina Menegon and Rosângela Gonçalves Peccinini 1 Lapdesf - Laboratório de Pesquisa e Desenvolvimento de Fármacos, Departamento de Fármacos e Medicamentos, Faculdade de Ciências Farmacêuticas – UNESP Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil; E-mail: jeanleandrosantos@.br (J.L.d.S.) 2 Departamento de Princípios Ativos, Naturais e Toxicologia, Faculdade de Ciências Farmacêuticas – UNESP Rodovia Araraquara Jaú Km. 01, 14801-902, Araraquara, SP, Brazil; E-mail: peccinin@fcfar.unesp.br (R.G.P.) * Author to whom correspondence should be addressed; E-mail: chungmc@fcfar.unesp.br. Received: 12 June 2009; in revised form: 7 August 2009 / Accepted: 13 August 2009 / Published: 26 August 2009 Abstract: The compound 1-(2,6-dichlorophenyl)indolin-2-one (1), planned as a pro-drug of diclofenac (2), was easily synthesized in 94% yield by an intramolecular reaction in the presence of coupling agent (i.e., EDC). Compound 1 showed anti-inflammatory and analgesic activity without gastro-ulcerogenic effects. The chemical and enzymatic hydrolysis profile of the lactam deriva