BIOMAT Database Logo BIOMAT Database Logo

Synthesis and biological evaluation of a series of multi-target N-substituted cyclic imide derivatives with potential antipsychotic effect. 2018

Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
CAS Key Laboratory for Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China.

In the present study, a series of multi-target N-substituted cyclic imide derivatives which possessed potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties were synthesized and evaluated as potential antipsychotics. Among these compounds, (3aR,4R,7S,7aS)-2-(4-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)butyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione hydrochloride (3d) held a promising pharmacological profile. 3d not only showed potent and balanced in vitro activities on D2/5-HT1A/5-HT2A receptors, but also endowed with low to moderate activities on 5-HT2C, H1, α1A, M3 receptors and hERG channel, suggesting a low liability to induce side effects such as weight gain, orthostatic hypotension and QT prolongation. In animal behavioral studies, 3d reduced phencyclidine-induced hyperlocomotion with a high threshold for catalepsy induction. Compound 3d was selected as a potential antipsychotic candidate for further development.

UI MeSH Term Description Entries
D007094 Imides Organic compounds containing two acyl groups bound to NITROGEN. Imide
D008124 Locomotion Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. Locomotor Activity,Activities, Locomotor,Activity, Locomotor,Locomotor Activities
D008297 Male Males
D008813 Mice, Inbred ICR An inbred strain of mouse that is used as a general purpose research strain, for therapeutic drug testing, and for the genetic analysis of CARCINOGEN-induced COLON CANCER. Mice, Inbred ICRC,Mice, ICR,Mouse, ICR,Mouse, Inbred ICR,Mouse, Inbred ICRC,ICR Mice,ICR Mice, Inbred,ICR Mouse,ICR Mouse, Inbred,ICRC Mice, Inbred,ICRC Mouse, Inbred,Inbred ICR Mice,Inbred ICR Mouse,Inbred ICRC Mice,Inbred ICRC Mouse
D010622 Phencyclidine A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust. 1-(1-Phenylcyclohexyl)piperidine,Angel Dust,CL-395,GP-121,Phencyclidine Hydrobromide,Phencyclidine Hydrochloride,Sernyl,Serylan,CL 395,CL395,Dust, Angel,GP 121,GP121
D002375 Catalepsy A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions. Cerea Flexibilitas,Flexibility, Waxy,Anochlesia,Anochlesias,Catalepsies,Flexibilitas, Cerea,Flexibilities, Waxy,Waxy Flexibilities,Waxy Flexibility
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

Related Publications

Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Synthesis and biological evaluation of a series of substituted N-alkoxyimides and -amides as potential atypical antipsychotic agents.
March 1991, Journal of medicinal chemistry,
Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Synthesis of aminomethyl-substituted cyclic imide derivatives for evaluation as anticonvulsants.
October 1983, Journal of medicinal chemistry,
Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Synthesis and study of some new N-substituted imide derivatives as potential anticancer agents.
April 2005, Farmaco (Societa chimica italiana : 1989),
Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Synthesis and biological evaluation of N(9)-substituted harmine derivatives as potential anticancer agents.
August 2016, Bioorganic & medicinal chemistry letters,
Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Synthesis and biological evaluation of N-substituted polycyclic imides derivatives.
January 2013, Acta poloniae pharmaceutica,
Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Synthesis, biological evaluation and docking studies of N-substituted resveratrol derivatives.
April 2024, Fitoterapia,
Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Synthesis and biological evaluation of novel flavanone derivatives as potential antipsychotic agents.
March 2017, Chemical biology & drug design,
Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Rational modification, synthesis and biological evaluation of N-substituted phthalazinone derivatives designed to target interleukine-15 protein.
June 2021, Bioorganic & medicinal chemistry,
Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Synthesis and biological evaluation of a new class of multi-target heterocycle piperazine derivatives as potential antipsychotics.
May 2021, RSC advances,
Mingshuo Xu, and Yu Wang, and Feipu Yang, and Chunhui Wu, and Zhen Wang, and Bin Ye, and Xiangrui Jiang, and Qingjie Zhao, and Jianfeng Li, and Yongjian Liu, and Junchi Zhang, and Guanghui Tian, and Yang He, and Jingshan Shen, and Hualiang Jiang
Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives.
September 2006, Acta pharmacologica Sinica,
Copied contents to your clipboard!