title: Design, synthesis, and evaluation of indolebutylamines as a novel class of selective dopamine D3 receptor ligands.
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 compound 11q binds to dopamine 3 receptor with a Ki 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.
authors.affiliation: Department of Medicinal Chemistry & Key Laboratory of Smart Drug Delivery, Ministry of Education & PLA, School of Pharmacy, Fudan University, Shanghai, 201203, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Du
authors.forename: Lili
authors.initials: L
authors.lastname: Xu
authors.forename: Jiye
authors.initials: J
authors.lastname: Huang
authors.forename: Kunqian
authors.initials: K
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Weili
authors.initials: W
authors.lastname: Zhao
authors.forename: Xuechu
authors.initials: X
authors.lastname: Zhen
authors.forename: Wei
authors.initials: W
authors.lastname: Fu
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002082:Butylamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D020134:Catalytic Domain; D018492:Dopamine Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011485:Protein Binding; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000083:Acetanilides; D002082:Butylamines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007211:Indoles; D008024:Ligands; C587497:N-cyclohexyl-2-(4-(4-(5-fluoro-1H-indol-3-yl)butyl)piperazin-1-yl)-N-(2-methoxyphenyl)acetamide; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C030374:indole
keywords: dopamine 3 receptor; indolebutylamine; pharmacophore model; selectivity; structure-activity relationship