Synthesis and antiemetic activity of 1,2,3,9-tetrahydro-9-methyl-3-(4-substituted-piperazin-1-ylmethyl)-4H-carbazol-4-one derivatives |
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Authors: | Qigui Xu Tianyu Liu Rui Tian Qingeng Li Deyin Ma |
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Institution: | (1) School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China;(2) Southwest Synthetic Pharmaceutical Corporation Limited, Chongqing, 401147, China |
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Abstract: | 5-HT3 receptor antagonists, such as Ondansetron, are used for anti-emesis after chemotherapy, radiotherapy 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 monophenylhydrazone (2). 1,2,3,9-Tetrahydro-4H-carbazol-4-one (3) was prepared from 2
via cyclization and rearranged in the presence of ZnCl2. 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-tetrahydro-9-methyl-3-(4-substituted-piperazin-1-ylmethyl)-4H-carbazol-4-one derivatives (6a–6i) were synthesized 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.
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Translated from Chinese Journal of Organic Chemistry, 2008, 28(2) (in Chinese) |
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Keywords: | 5-HT3 receptor antagonist 1 2 3 9-tetrahydro-4H-carbazol-4-one Mannich reaction antiemetic |
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