1. Synthesis and evaluation of new coumarin derivatives as potential atypical antipsychotics.
- Author
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Chen, Yin, Lan, Yu, Wang, Songlin, Zhang, Heng, Xu, Xiangqing, Liu, Xin, Yu, Minquan, Liu, Bi-Feng, and Zhang, Guisen
- Subjects
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COUMARIN derivatives , *ANTIPSYCHOTIC agents , *CHEMICAL synthesis , *DOPAMINE receptors , *SEROTONIN receptors , *APOMORPHINE - Abstract
Abstract: In this paper, we report the synthesis of novel, potential antipsychotic coumarin derivatives combining potent dopamine D2, D3 and serotonin 5-HT1A, 5-HT2A receptors properties. We describe the structure activity relationship that leads us to the promising derivative: 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-6-methyl-2,3-dihydrocyclopenta[c]chromen-4(1H)-one 27. The unique pharmacological features of compound 27 are a high affinity for dopamine D2, D3 and serotonin 5-HT1A, 5-HT2A receptors, together with a low affinity for H1 receptor (to reduce the risk of obesity under chronic treatment). In animal models, compound 27 inhibited apomorphine-induced climbing and MK-801-induced hyperactivity without observable catalepsy at the highest dose tested. In particular, compound 27 was more potent than clozapine. [Copyright &y& Elsevier]
- Published
- 2014
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