Syntheses Of Derivatives Of Ondansetron And Primary Research On Anti-Emesis Activity

Ondansetron Hydrochloride is a high effective and high selective 5-HT3 receptor antagonist and is used on anti-emesis after chemotherapy and radiotherapy and postoperation. It has been widely used in the world since it was produced by GLAXO Ltd in 1980's. Ondansetron Hydrochloride was synthesized in five steps starting from 1,3- cyclohexandione and phenylhydrazine Hydrochloride. by condensing, cyclizing, methylating, aminomethylating and substituting with 2-methyl- imidazole. The success of Ondansetron in market leads to further research into 5-HT3 receptor antagonist and rapid development of research on the structure-activity relationship of 5-HT3 receptor antagonist.M.F.Hilbert and his coworkers collected the data of 5-HT3 antagonists and studied it with soft Sybyl5.2 Molecular Modeling. They believed that its base structure be most likely include an aromatic ring,an alkali center and a carbonyl group which is at the same flat surface with the aromatic ring.and there should be a definitive distance between carbonyl group and alkali center.According to the structure-activity relationship,We have synthesized a series of un-reported derivative of Ondansetron taking 1,2,3,9-tetrahydro-9-methyl -3[(dimethylamino)methyl]-carbazol-4-one as key intermediate, Substitut- ing dimethylamine of 14-C of the key intermediate with saturated cycloaminium and fatty amine.The structure is well conformed by IR,UV,MS,NMR and primary pharmacodynamics study has been done.