title: Discovery of TRPV1 antagonist ABT-116.
abstract: The synthesis and SAR of a series of indazole TRPV1 antagonists leading to the discovery of 21 (ABT-116) is described. Biological studies demonstrated potent in vitro and in vivo activity for 21, as well as suitable physicochemical and pharmacokinetic properties for advancement to clinical development for pain management.
authors.affiliation: Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Dept R4PM, AP10-207, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. brian.s.brown@abbott.com
authors.forename: Brian S
authors.initials: BS
authors.lastname: Brown
authors.forename: Ryan
authors.initials: R
authors.lastname: Keddy
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Perner
authors.forename: Stanley
authors.initials: S
authors.lastname: DiDomenico
authors.forename: John R
authors.initials: JR
authors.lastname: Koenig
authors.forename: Tammie K
authors.initials: TK
authors.lastname: Jinkerson
authors.forename: Steven M
authors.initials: SM
authors.lastname: Hannick
authors.forename: Heath A
authors.initials: HA
authors.lastname: McDonald
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Bianchi
authors.forename: Prisca
authors.initials: P
authors.lastname: Honore
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Puttfarcken
authors.forename: Robert B
authors.initials: RB
authors.lastname: Moreland
authors.forename: Kennan C
authors.initials: KC
authors.lastname: Marsh
authors.forename: Connie R
authors.initials: CR
authors.lastname: Faltynek
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000700:Analgesics / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D006801:Humans; D007191:Indazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
chemical_list: C551310:ABT 116; D000700:Analgesics; D007191:Indazoles; D010671:Phenylurea Compounds; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human