Synthesis and preliminary CNS depressant activity evaluation of new 3-[(3-substituted-5-methyl-4-thiazolidinon-2-ylidene)hydrazono]-1H-2-indolinones and 3-[(2-thioxo-3-substituted-4,5-imidazolidine-dion-1-yl)imino]-1H-2-indolinones

Abstract

A series of (+/-) 3-[(3-substituted-5-methyl-4-thiazolidinon-2- ylidene)hydrazono]-1H-2-indolinones (2a-h) and 3-[(2-thioxo-3-substituted-4,5- imidazolidinedion-1-yl)imino]-1H-2-indolinones (3a-g) were synthesized by the cyclization of 3-(4-substituted-thiosemicarbazono)-1H-2-indolinones (la-h) with ethyl 2-bromopropionate in anhydrous ethanolic medium and oxalyl chloride in anhydrous diethyl ether, respectively. The structures of 2 and 3 were confirmed by analytical and spectral data (IR, H-1 NMR, C-13 NMR, and EIMS) The configuration of 3 was assigned on the basis of H-1 NMR and C-13 NMR data. 2c, 2d, 2g, 2h, and 3a-g were evaluated for anticonvulsant activity against maximal electroshock (MES) and subcutaneous pentylenetetrazol (ScMet) induced seizures. Among the compounds tested, only 2d exhibited some activity in anticonvulsant identification (Phase I) trials in mice. 2a, 2b, 2d, 2g, 2h, and 3a-g were additionally tested for potentiating effects on pentobarbital induced hypnosis in mice. All of the test compounds increased the sleeping time of pentobarbital significantly (p < 0.05) and the most potent compound was found to be 3a.