title: Design, synthesis and biological evaluation of novel tetrahydroisoquinoline quaternary derivatives as peripheral κ-opioid receptor agonists.
abstract: A novel series of tetrahydroisoquinoline quaternary derivatives 4 were synthesized as peripheral κ-opioid receptor agonists. All the target compounds were evaluated in κ-opioid receptor binding assays, and compounds 4l, 4m, and 4n exhibited high affinity for κ-opioid receptor. Furthermore, compound 4l (κKi=0.94nM) produced potent antinociceptive activity in the mouse acetic acid-induced writhing assay, with lower sedative side effects than the parent compound MB-1c.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zongjie
authors.initials: Z
authors.lastname: Gan
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Dechuan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Ling
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Song
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China. Electronic address: xu_yungen@hotmail.com.
authors.forename: Yungen
authors.initials: Y
authors.lastname: Xu
mesh_terms: D019342:Acetic Acid; D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D015195:Drug Design; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D011485:Protein Binding / Q000187:drug effects; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000700:Analgesics; D006993:Hypnotics and Sedatives; D017473:Receptors, Opioid, kappa; D044005:Tetrahydroisoquinolines; D019342:Acetic Acid
keywords: Peripheral; Tetrahydroisoquinoline quaternary derivatives; κ-Opioid receptor agonists