4-Aminoquinoline melanin-concentrating hormone 1-receptor (MCH1R) antagonists.
Structure-activity relationships of a 4-aminoquinoline MCH1R antagonist lead series were explored by synthesis of analogs with modifications at the 2-, 4-, and 6-positions of the original HTS hit. Improvements to the original screening lead included lipophilic groups at the 2-position and biphenyl, cyclohexyl phenyl, and hydrocinnamyl carboxamides at the 6-position. Modifications of the 4-amino group were not well tolerated.
Jiang
Jinlong
J
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA.
Lin
Peter
P
Hoang
Myle
M
Chang
Lehua
L
Tan
Carina
C
Feighner
Scott
S
Palyha
Oksana C
OC
Hreniuk
Donna L
DL
Pan
Jie
J
Sailer
Andreas W
AW
Morin
Nancy R
NR
MacNeil
Douglas J
DJ
Howard
Andrew D
AD
Van der Ploeg
Lex H T
LH
Goulet
Mark T
MT
DeVita
Robert J
RJ
D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; C103263:MCHR1 protein, human; D017481:Receptors, Somatostatin; C001920:4-aminoquinoline