Design, Synthesis, and Evaluation of Indolebutylamines as a Novel Class of Selective Dopamine D3 Receptor Ligands. (22nd August 2013)

• Record Type: Journal Article
• Authors: Du, Peng; Xu, Lili; Huang, Jiye; Yu, Kunqian; Zhao, Rui; Gao, Bo; Jiang, Hualiang; Zhao, Weili; Zhen, Xuechu; Fu, Wei
• Is Part Of: Chemical biology & drug design. Volume 82:Number 3(2013:Sep.)
• Page Start: 326
• Page End: 335
• Publication Date: 2013-08-22
• Subjects: dopamine 3 receptor -- indolebutylamine -- pharmacophore model -- selectivity -- structure‐activity relationship; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12158
• Languages: English
• ISSNs: 1747-0277

Abstract

Abstract : A series of indolebutylamine derivatives were designed, synthesized, and evaluated as a novel class of selective ligands for the dopamine 3 receptor. The most potent compound11q binds to dopamine 3 receptor with a K i value of 124 nm and displays excellent selectivity over the dopamine 1 receptor and dopamine 2 receptor. Investigation based on structural information indicates that site S182 located in extracellular loop 2 may account for high selectivity of compounds. Interaction models of the dopamine 3 receptor‐11q complex and structure‐activity relationships were discussed by integrating all available experimental and computational data with the eventual aim to discover potent and selective ligands to dopamine 3 receptor. Abstract : Using a strategy that combines synthetic chemistry, binding assays and a set of computational approach, we designed a series of indolebutylamine derivatives as a new type of highly selective dopamine 3 receptor were identified and the structure‐activity relationships was investigated to understand the recognition of this type of dopamine 3 receptor ligands.