Potent, selective MCH-1 receptor antagonists.
This paper describes the lead optimization of a new series of potent, selective, orally bioavailable, brain-penetrant MCH-1 receptor antagonists. A major focus of the work was to achieve a selectivity profile appropriate for in vivo efficacy studies and safety.
Erickson
Shawn D
SD
Discovery Chemistry, Hoffmann-La Roche, Inc., 340 Kingsland Street, Nutley, NJ 07110, USA.
Banner
Bruce
B
Berthel
Steven
S
Conde-Knape
Karin
K
Falcioni
Fiorenza
F
Hakimi
Irina
I
Hennessy
Bernard
B
Kester
Robert F
RF
Kim
Kyungjin
K
Ma
Chun
C
McComas
Warren
W
Mennona
Francis
F
Mischke
Steven
S
Orzechowski
Lucy
L
Qian
Yimin
Y
Salari
Hamid
H
Tengi
John
J
Thakkar
Kshitij
K
Taub
Rebecca
R
Tilley
Jefferson W
JW
Wang
Hong
H
D000577:Amides / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006801:Humans; D007189:Indans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D007700:Kinetics; D010880:Piperidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
D000577:Amides; D001562:Benzimidazoles; D007189:Indans; C103263:MCHR1 protein, human; D010880:Piperidines; D017481:Receptors, Somatostatin