title: Synthesis and biological evaluation of 2-substituted quinoline 6-carboxamides as potential mGluR1 antagonists for the treatment of neuropathic pain.
abstract: A series of 2-amino and 2-methoxy quinoline-6-carboxamide derivatives have been synthesized and their metabotropic glutamate receptor type 1 (mGluR1) antagonistic activities were evaluated in a functional cell-based assay. The compound 13c showed the highest potency with IC50 value of 2.16 µM against mGluR1. Finally, in vivo evaluation of 13c in the rat spinal nerve ligation (SNL) model exhibited weak analgesic effects with regard to both mechanical allodynia and cold allodynia.
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology (KIST).
authors.forename: Younghee
authors.initials: Y
authors.lastname: Kim
authors.forename: Jiwon
authors.initials: J
authors.lastname: Son
authors.forename: Juhyeon
authors.initials: J
authors.lastname: Kim
authors.forename: Du-Jong
authors.initials: DJ
authors.lastname: Baek
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Lim
authors.forename: Jae Kyun
authors.initials: JK
authors.lastname: Lee
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.forename: Sun-Joon
authors.initials: SJ
authors.lastname: Min
authors.forename: Yong Seo
authors.initials: YS
authors.lastname: Cho
mesh_terms: D000818:Animals; D003080:Cold Temperature; D004305:Dose-Response Relationship, Drug; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D009437:Neuralgia / Q000188:drug therapy*; D010147:Pain Measurement / Q000187:drug effects; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D051638:Ether-A-Go-Go Potassium Channels; C000595927:N-ethyl-2-(piperidin-1-yl)quinoline-6-carboxamide; D010880:Piperidines; D011804:Quinolines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1