5-HT3 receptor antagonists, such as Ondanse-tron, are used for anti-emesis after chemotherapy, radio-therapy and operations. Some Ondansetron analogs possessing piperazine ring as side chains were synthesized in our lab. Thus, one of the two carbonyl groups of starting material 1,3-cyclohexandione (1) was condensed with phenylhydrazine hydrochloride to form monophenylhy-drazone (2). 1,2,3,9-Tetrahydro-4H-carbazol-4-one (3) was prepared from 2 via cyclization and rearranged in the presence of ZnC12. Through a methylation reaction,compound 3 was converted to 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one (4). 3-Dimethylaminomethyl substituted compound (5) was synthesized from 4 by a Mannich reaction in glacial acetic acid. Nine novel 1,2,3,9-t etrahydro-9-methyl- 3 - (4- sub stituted-pip erazin- 1 -ylmethyl)- 4H-carbazol-4-one derivatives (6a--6i) were sy-nthesized through nucleophilic substitution reaction of 5 with piperazines. The structures of all the target compounds were determined by elemental analysis, IR,MS, 1H NMR and 13C NMR spectra. The results of preliminary pharmacological test show that part of the novel compounds have antiemetic activity comparable to that of the control Ondansetron.