Novel benzimidazole-based MCH R1 antagonists.
The identification of an MCH R1 antagonist screening hit led to the optimization of a class of benzimidazole-based MCH R1 antagonists. Structure-activity relationships and efforts to optimize pharmacokinetic properties are detailed along with the demonstration of the effectiveness of an MCH R1 antagonist in an animal model of obesity.
Carpenter
Andrew J
AJ
Metabolic and Viral Diseases Centre of Excellence for Drug Discovery, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA. andrew.j.carpenter@gsk.com
Al-Barazanji
Kamal A
KA
Barvian
Kevin K
KK
Bishop
Michael J
MJ
Britt
Christy S
CS
Cooper
Joel P
JP
Goetz
Aaron S
AS
Grizzle
Mary K
MK
Hertzog
Donald L
DL
Ignar
Diane M
DM
Morgan
Ronda O
RO
Peckham
Gregory E
GE
Speake
Jason D
JD
Swain
Will R
WR
D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D001823:Body Composition; D004305:Dose-Response Relationship, Drug; D051379:Mice; D023421:Models, Animal; D009765:Obesity / Q000188:drug therapy*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D015431:Weight Loss / Q000187:drug effects
D001562:Benzimidazoles; C491209:Mchr1 protein, mouse; D017481:Receptors, Somatostatin; C031000:benzimidazole