Discovery of TRPV1 antagonist ABT-116

Brian S Brown; Ryan Keddy; Richard J Perner; Stanley DiDomenico; John R Koenig; Tammie K Jinkerson; Steven M Hannick; Heath A McDonald; Bruce R Bianchi; Prisca Honore; Pamela S Puttfarcken; Robert B Moreland; Kennan C Marsh; Connie R Faltynek; Chih-Hung Lee

doi:10.1016/j.bmcl.2010.04.047

Discovery of TRPV1 antagonist ABT-116

Bioorg Med Chem Lett. 2010 Jun 1;20(11):3291-4. doi: 10.1016/j.bmcl.2010.04.047. Epub 2010 Apr 14.

Authors

Brian S Brown¹, Ryan Keddy, Richard J Perner, Stanley DiDomenico, John R Koenig, Tammie K Jinkerson, Steven M Hannick, Heath A McDonald, Bruce R Bianchi, Prisca Honore, Pamela S Puttfarcken, Robert B Moreland, Kennan C Marsh, Connie R Faltynek, Chih-Hung Lee

Affiliation

¹ 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

PMID: 20457518
DOI: 10.1016/j.bmcl.2010.04.047

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.

MeSH terms

Analgesics / pharmacokinetics
Analgesics / pharmacology*
Animals
Humans
Indazoles / pharmacokinetics
Indazoles / pharmacology*
Phenylurea Compounds / pharmacokinetics
Phenylurea Compounds / pharmacology*
Rats
Structure-Activity Relationship
TRPV Cation Channels / antagonists & inhibitors*

Substances

ABT 116
Analgesics
Indazoles
Phenylurea Compounds
TRPV Cation Channels
TRPV1 protein, human