title: Synthesis of carbamide derivatives bearing tetrahydroisoquinoline moieties and biological evaluation as analgesia drugs in mice.
abstract: Transient receptor potential vanilloid 1 (TRPV1) is a ligand-gated non-selective cation channel that is considered to be an important pain integrator. Tetrahydroisoquinoline, the prototypical antagonist of TRPV1, has a clear therapeutic potential. Here, a series of carbamide derivatives of tetrahydroisoquinoline were designed and synthesized. Preliminary biological tests suggested that the compounds I 1, I 2, and I 9 had favorable TRPV1 antagonism activity. In further studies, I 1 exhibited better antinociceptive activity than the positive control BCTC in diverse pain models. All of these results suggested that I 1 can be considered as the lead candidate for the further development of antinociceptive drugs.
authors.affiliation: State Key Laboratory of Natural Medicines, Center of Drug Discovery, China Pharmaceutical University, Nanjing, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Qiu
authors.forename: Jingjie
authors.initials: J
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Deng
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.forename: Haiyan
authors.initials: H
authors.lastname: Lin
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D051379:Mice; D015394:Molecular Structure; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control* / Q000523:psychology; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D044005:Tetrahydroisoquinolines; D014508:Urea
keywords: Analgesia drugs; Tetrahydroisoquinoline derivatives; Transient receptor potential vanilloid 1 antagonist