Synthesis and evaluation of 2-amino-8-alkoxy quinolines as MCHr1 antagonists. Part 1.
A high-throughput screen was performed in order to identify chemotypes that are bound by the melanin concentrating hormone receptor-1 (MCHr1). A novel 2-amino-8-alkoxyquinoline compound (1) was identified and subsequently optimized using a parallel and automated procedure for the rapid production of multiple analogs. The structure-activity relationships that emerged from this effort are described, along with selected pharmacokinetic parameters of compound (d)-61 when dosed orally in diet-induced obese mice.
Souers
Andrew J
AJ
Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. andrew.souers@abbott.com
Wodka
Dariusz
D
Gao
Ju
J
Lewis
Jared C
JC
Vasudevan
Anil
A
Gentles
Robert
R
Brodjian
Sevan
S
Dayton
Brian
B
Ogiela
Christopher A
CA
Fry
Dennis
D
Hernandez
Lisa E
LE
Marsh
Kennan C
KC
Collins
Christine A
CA
Kym
Philip R
PR
D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis*; D051379:Mice; D011804:Quinolines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D019440:Anti-Obesity Agents; C491209:Mchr1 protein, mouse; D011804:Quinolines; D017481:Receptors, Somatostatin