Discovery of potent, selective, and orally bioavailable 3H-spiro[isobenzofuran-1,4'-piperidine] based melanocortin subtype-4 receptor agonists.
Design, synthesis, and SAR of a series of 3H-spiro[isobenzofuran-1,4'-piperidine] based compounds as potent, selective and orally bioavailable melanocortin subtype-4 receptor (MC4R) agonists are disclosed.
Guo
Liangqin
L
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. liangqin_guo@merck.com
Ye
Zhixiong
Z
Liu
Jian
J
He
Shuwen
S
Bakshi
Raman K
RK
Sebhat
Iyassu K
IK
Dobbelaar
Peter H
PH
Hong
Qingmei
Q
Jian
Tianying
T
Dellureficio
James P
JP
Tsou
Nancy N
NN
Ball
Richard G
RG
Weinberg
David H
DH
MacNeil
Tanya
T
Tang
Rui
R
Tamvakopoulos
Constantin
C
Peng
Qianping
Q
Chen
Howard Y
HY
Chen
Airu S
AS
Martin
William J
WJ
MacIntyre
D Euan
DE
Strack
Alison M
AM
Fong
Tung M
TM
Wyvratt
Matthew J
MJ
Nargund
Ravi P
RP
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000378:metabolism; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008968:Molecular Conformation; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry; D013329:Structure-Activity Relationship
D010880:Piperidines; D044105:Receptor, Melanocortin, Type 4; D013141:Spiro Compounds; C032727:piperidine