Optimization of privileged structures for selective and potent melanocortin subtype-4 receptor ligands.
Design, syntheses and structure-activity relationships of N-acetylated piperazine privileged structures containing MC4R agonist compounds were described. The most potent derivatives were low nM MC4R selective full agonists. Several compounds from the series had modest pharmacokinetic properties.
Hong
Qingmei
Q
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. qingmei_hong@merck.com
Bakshi
Raman K
RK
Dellureficio
James
J
He
Shuwen
S
Ye
Zhixiong
Z
Dobbelaar
Peter H
PH
Sebhat
Iyassu K
IK
Guo
Liangqin
L
Liu
Jian
J
Jian
Tianying
T
Tang
Rui
R
Kalyani
Rubana N
RN
Macneil
Tanya
T
Vongs
Aurawan
A
Rosenblum
Charles I
CI
Weinberg
David H
DH
Peng
Qingping
Q
Tamvakopoulos
Constantin
C
Miller
Randy R
RR
Stearns
Ralph A
RA
Cashen
Doreen
D
Martin
Willian J
WJ
Chen
Airu S
AS
Metzger
Joseph M
JM
Chen
Howard Y
HY
Strack
Allison M
AM
Fong
Tung M
TM
Maclntyre
Euan
E
Van der Ploeg
Lex H T
LH
Wyvratt
Matthew J
MJ
Nargund
Ravi P
RP
D000818:Animals; D006801:Humans; D008024:Ligands; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D008024:Ligands; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4; D000077489:Piperazine