One of the two carbonyl groups of starting material 1,3-cyclohexandione (1) was condensed with phenylhydrazine hydrochloride to form monophenylhydrazone (2). 1,2,3,9-tetrahydro-carbazol-4-one (3) was prepared from 2 through cyclization and rearrangement in the presence of ZnCl₂. Through methylation reaction, compound 3 is converted to 9-methyl-1,2,3,9-tetrahydro-carbazol-4-one (4). 3-Dimethylaminomethyl- substituted compound (5) was synthesized from 4 by Mannich reaction in glacial acetic acid. Nine novel 3-(4-substituted-piperazin-1-ylmethyl)-1,2,3,9-tetrahydro-carbazol-4-one derivatives 6a～6i were synthesized via nucleophilic substitution reaction of 5 with piperazines. The struc-tures 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.

Key words: 1,2,3,9-tetrahydro-carbazol-4-one, 5-HT₃ receptor antagonist, Mannich reaction, an-tiemetic