1. Design, Synthesis and Biological Investigation of Flavone Derivatives as Potential Multi-Receptor Atypical Antipsychotics.
- Author
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Gao, Lanchang, Yang, Zhengge, Xiong, Jiaying, Hao, Chao, Ma, Ru, Liu, Xin, Liu, Bi-Feng, Jin, Jian, Zhang, Guisen, and Chen, Yin
- Subjects
BIOSYNTHESIS ,DOPAMINE antagonists ,SEROTONIN receptors ,ANTIPSYCHOTIC agents ,DOPAMINE receptors ,ORTHOSTATIC hypotension ,RISPERIDONE ,FLAVONES - Abstract
The design of a series of novel flavone derivatives was synthesized as potential broad-spectrum antipsychotics by using multi-receptor affinity strategy between dopamine receptors and serotonin receptors. Among them, 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl) piperidin- 1-yl) butoxy)-2,2-dimethylchroman-4-one (6j) exhibited a promising preclinical profile. Compound 6j not only showed high affinity for dopamine D
2 , D3 , and serotonin 5-HT1A , 5-HT2A receptors, but was also endowed with low to moderate activities on 5-HT2C , α1 , and H1 receptors, indicating a low liability to induce side effects such as weight gain, orthostatic hypotension and QT prolongation. In vivo behavioral studies suggested that 6j has favorable effects in alleviating the schizophrenia-like symptoms without causing catalepsy. Taken together, compound 6j has the potential to be further developed as a novel atypical antipsychotic. [ABSTRACT FROM AUTHOR]- Published
- 2020
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