Design, synthesis and pharmacological evaluation of indolylsulfonamide amines as potent and selective 5-HT6 receptor antagonists

被引：0
|
作者：
Nirogi, Ramakrishna V. S. [1 ]
Bandyala, Thrinath Reddy [1 ,2 ]
Reballi, Veena [1 ]
Konda, Jagadishu Babu [1 ]
Daulatabad, Anand V. [1 ]
Khagga, Mukkanti [2 ]
机构：
[1] Suven Life Sci Ltd, Discovery Res Med Chem, Serene Chambers, Hyderabad, Andhra Pradesh, India
[2] Jawaharlal Nehru Technol Univ Hyderabad, Inst Sci & Technol, Ctr Chem Sci & Technol, Hyderabad, Andhra Pradesh, India
来源：
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2015年 / 30卷 / 01期
关键词：
5-Hydroxytryptamine(6) receptor; central nervous system; cognition; novel object recognition test; structure activity relationship; water maze; SEROTONIN RECEPTORS; POLYMORPHISM C267T; ASSOCIATION ANALYSIS; BINDING; LIGANDS; GENE; SCHIZOPHRENIA; MUTAGENESIS; ANALOGS; AGENTS;
D O I：
10.3109/14756366.2014.889126
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
A series of N'-[3-(indole-1-sulfonyl)aryl]-N,N-dimethyl ethane-1,2-diamines and N'-[3-(indole-1-sulfonyl) aryl]-N, N-dimethyl propane-1,3-diamines was designed and synthesized as 5-HT6 receptor ligands. These compounds, when screened in a functional reporter gene-based assay, displayed potent antagonistic activity with K-b values in the range of 1.8-60 nM. The lead compound 9y has shown good ADME surrogate properties, acceptable pharmacokinetic profile and is active in animal models of cognition like novel object recognition test and Morris water maze. It was selected for detailed profiling.
引用
收藏
页码：85 / 97
页数：13
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