Synthesis and antiemetic activity of 1,2,3,9-tetrahydro-9-methyl-3-(4-substituted-piperazin-1-ylmethyl)-4<italic>H</italic>-carbazol-4-one derivatives

doi:10.1007/s11458-009-0017-8

Front Chem Chin

2009, Vol. 4

Issue (1) : 63-68 https://doi.org/10.1007/s11458-009-0017-8

RESEARCH ARTICLE

Synthesis and antiemetic activity of 1,2,3,9-tetrahydro-9-methyl-3-(4-substituted-piperazin-1-ylmethyl)-4H-carbazol-4-one derivatives

Qigui XU¹, Tianyu LIU¹, Rui TIAN¹, Qingeng LI¹(

), Deyin MA²

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 2via 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.

Keywords 5-HT₃ receptor antagonist 1 2 3 9-tetrahydro-4H-carbazol-4-one Mannich reaction antiemetic

Corresponding Author(s): LI Qingeng,Email:liqingeng@cqmu.edu.cn

Issue Date: 05 March 2009

Cite this article:

Qigui XU,Tianyu LIU,Rui TIAN, et al. Synthesis and antiemetic activity of 1,2,3,9-tetrahydro-9-methyl-3-(4-substituted-piperazin-1-ylmethyl)-4H-carbazol-4-one derivatives[J]. Front Chem Chin, 2009, 4(1): 63-68.

URL:

https://academic.hep.com.cn/fcc/EN/10.1007/s11458-009-0017-8
https://academic.hep.com.cn/fcc/EN/Y2009/V4/I1/63

Fig.1 Ondansetron

Fig.2 Synthesis of compounds -

Tab.1 The latent period to retches and the frequency of retches of groups (±, ＝ 6)

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