Synthesis, structure-activity relationships, and biological evaluation of a series of benzamides as potential multireceptor antipsychotics

doi:10.1016/j.bmcl.2016.04.087

	Synthesis, structure-activity relationships, and biological evaluation of a series of benzamides as potential multireceptor antipsychotics
	Yang, Feipu 1; Jiang, Xiangrui1 ; Li, Jianfeng1 ; Wang, Yu 1; Liu, Yongjian 2; Bi, Minghao 2; Wu, Chunhui 2; Zhao, Qingjie1 ; Chen, Weiming 2; Yin, Jingjing 2
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	2016-07-01
卷号	26 期号:13 页码:3141-3147
关键词	D-2 5-HT1A 5-HT2A PCP-induced hyperactivity Catalepsy
ISSN号	0960-894X
DOI	10.1016/j.bmcl.2016.04.087
文献子类	Article
英文摘要	In the present study, a series of benzamides, endowed with potent dopamine D-2, serotonin 5-HT1A and 5-HT2A receptors properties, was synthesized and evaluated as potential antipsychotics. Among them, 3-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl)butoxy)-N-methylbenzamide (21) and its fluoro-substituted analogue (22) held the best pharmacological binding profiles. They not only presented potent activities for D-2, 5-HT1A, and 5-HT2A receptors, but were also endowed with low activities for 5-HT2C, H-1 receptors and hERG channels, suggesting a low propensity of inducing weight gain and QT prolongation. In animal models, compounds 21 and 22 reduced phencyclidine-induced hyperactivity with a high threshold for catalepsy induction. It thus provides potential candidates for further preclinical studies. (C) 2016 Elsevier Ltd. All rights reserved.
资助项目	Chinese Ministry of National Science and Technology create significant new drugs, special major science and technology[2013ZX09507001]
WOS关键词	MAJOR DEPRESSIVE DISORDER ; 5-HT1A RECEPTOR AGONIST ; INDUCED WEIGHT-GAIN ; PARKINSONS-DISEASE ; ATYPICAL ANTIPSYCHOTICS ; SCHIZOPHRENIA ; EFFICACY ; DRUG ; HYPERACTIVITY ; PHARMACOLOGY
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000377470600035
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/275979]
专题	药物化学研究室
通讯作者	Wang, Zhen; He, Yang
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China; 2.Topharman Shanghai Co Ltd, 1088 Chuansha Rd, Shanghai 201209, Peoples R China
推荐引用方式 GB/T 7714	Yang, Feipu,Jiang, Xiangrui,Li, Jianfeng,et al. Synthesis, structure-activity relationships, and biological evaluation of a series of benzamides as potential multireceptor antipsychotics[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2016,26(13):3141-3147.
APA	Yang, Feipu.,Jiang, Xiangrui.,Li, Jianfeng.,Wang, Yu.,Liu, Yongjian.,...&Shen, Jingshan.(2016).Synthesis, structure-activity relationships, and biological evaluation of a series of benzamides as potential multireceptor antipsychotics.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,26(13),3141-3147.
MLA	Yang, Feipu,et al."Synthesis, structure-activity relationships, and biological evaluation of a series of benzamides as potential multireceptor antipsychotics".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 26.13(2016):3141-3147.