1-(4-Amino-phenyl)-pyrrolidin-3-yl-amine and 6-(3-amino-pyrrolidin-1-yl)-pyridin-3-yl-amine derivatives as melanin-concentrating hormone receptor-1 antagonists.
Derivatives of 1-(4-amino-phenyl)-pyrrolidin-3-yl-amine and 6-(3-amino-pyrrolidin-1-yl)-pyridin-3-yl-amine were identified as potent and functionally active MCH-R1 antagonists. One compound with Ki = 2.3 nM demonstrated good oral bioavailability (32%) and in vivo efficacy in rats.
Huang
Charles Q
CQ
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Baker
Tracy
T
Schwarz
David
D
Fan
Jun
J
Heise
Christopher E
CE
Zhang
Mingzhu
M
Goodfellow
Val S
VS
Markison
Stacy
S
Gogas
Kathleen R
KR
Chen
Takung
T
Wang
Xiao-Chuan
XC
Zhu
Yun-Fei
YF
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001835:Body Weight; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008297:Male; D023421:Models, Animal; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
C491208:MCHR1 protein, rat; D011725:Pyridines; D011759:Pyrrolidines; D017481:Receptors, Somatostatin