Discovery of TRPV1 antagonist ABT-116.
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.
Brown
Brian S
BS
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
Keddy
Ryan
R
Perner
Richard J
RJ
DiDomenico
Stanley
S
Koenig
John R
JR
Jinkerson
Tammie K
TK
Hannick
Steven M
SM
McDonald
Heath A
HA
Bianchi
Bruce R
BR
Honore
Prisca
P
Puttfarcken
Pamela S
PS
Moreland
Robert B
RB
Marsh
Kennan C
KC
Faltynek
Connie R
CR
Lee
Chih-Hung
CH
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*
C551310:ABT 116; D000700:Analgesics; D007191:Indazoles; D010671:Phenylurea Compounds; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human