Synthesis, ex vivo and in vitro hydrolysis study of an indoline derivative designed as an anti-inflammatory with reduced gastric ulceration properties.
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 derivative 1 does not indicate conversion to diclofenac (2). This compound is a new non-ulcerogenic prototype for treatment of chronic inflammatory diseases.
Chung
Man Chin
MC
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. chungmc@fcfar.unesp.br
dos Santos
Jean Leandro
JL
Oliveira
Ednir Vizioli
EV
Blau
Lorena
L
Menegon
Renato Farina
RF
Peccinini
Rosângela Gonçalves
RG
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002351:Carrageenan; D000068579:Celecoxib; D004008:Diclofenac / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006868:Hydrolysis / Q000187:drug effects; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007769:Lactams / Q000097:blood / Q000737:chemistry; D008297:Male; D008958:Models, Molecular; D011720:Pyrazoles / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced*; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D007211:Indoles; D007769:Lactams; D011720:Pyrazoles; D013449:Sulfonamides; D004008:Diclofenac; D002351:Carrageenan; D000068579:Celecoxib