Design and synthesis of potent and selective 1,3,4-trisubstituted-2-oxopiperazine based melanocortin-4 receptor agonists.
The design and synthesis of a series of potent 1,3,4-trisubstituted-2-oxopiperazine based MC4 agonists are described. The tripeptidomimetic analogs (12a,b and 23) and the dipeptidomimetic 27 displayed single-nanomolar binding affinity and agonist potency for MC4R and excellent selectivity for MC4R relative to MC1R.
Tian
Xinrong
X
Procter & Gamble Pharmaceuticals, Health Care Research Center, Mason, OH 45040, USA. tian.x@hotmail.com
Mishra
Rajesh K
RK
Switzer
Adrian G
AG
Hu
X Eric
XE
Kim
Nick
N
Mazur
Adam W
AW
Ebetino
Frank H
FH
Wos
John A
JA
Crossdoersen
Doreen
D
Pinney
Beth B
BB
Farmer
Julie A
JA
Sheldon
Russell J
RJ
D015195:Drug Design; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D006146:Guanidines; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4