Aminopiperidine indazoles as orally efficacious melanin concentrating hormone receptor-1 antagonists.
The synthesis and biological evaluation of novel 3-amino indazole melanin concentrating hormone receptor-1 antagonists are reported, several of which demonstrated functional activity of less than 100nM. Compounds 19 and 28, two of the more potent compounds identified in this study, were characterized by high exposure in the brain and demonstrated robust efficacy when dosed in diet-induced obese mice.
Vasudevan
Anil
A
Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. Anil.Vasudevan@abbott.com
Souers
Andrew J
AJ
Freeman
Jennifer C
JC
Verzal
Mary K
MK
Gao
Ju
J
Mulhern
Mathew M
MM
Wodka
Derek
D
Lynch
John K
JK
Engstrom
Kenneth M
KM
Wagaw
Seble H
SH
Brodjian
Sevan
S
Dayton
Brian
B
Falls
Doug H
DH
Bush
Eugene
E
Brune
Michael
M
Shapiro
Robin D
RD
Marsh
Kennan C
KC
Hernandez
Lisa E
LE
Collins
Christine A
CA
Kym
Philip R
PR
D000284:Administration, Oral; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007191:Indazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D010880:Piperidines / Q000737:chemistry; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D014018:Tissue Distribution
D019440:Anti-Obesity Agents; D007191:Indazoles; C103263:MCHR1 protein, human; D010880:Piperidines; D017481:Receptors, Somatostatin; C032727:piperidine