Melanocortin subtype-4 receptor agonists containing a piperazine core with substituted aryl sulfonamides.
The biological activity for a set of melanocortin-4 receptor (MC4R) agonists containing a piperazine core with an ortho-substituted aryl sulfonamide is described. Compounds from this set had binding and functional activities at MC4R less than 30 nM. The most selective compound in this series was >25,000-fold more potent at MC4R than MC3R, and 490-fold more potent at MC4R than MC5R. This compound also reduced food intake after oral dosing at 25, 50, and 100 mg kg(-1) in fasted mice.
Fotsch
Christopher
C
Department of Chemistry Research and Discovery, Amgen Inc., One Amgen Center Drive, Mailstop 29-1-B, Thousand Oaks, CA 91320, USA. cfotsch@amgen.com
Han
Nianhe
N
Arasasingham
Premilla
P
Bo
Yunxin
Y
Carmouche
Michelle
M
Chen
Ning
N
Davis
James
J
Goldberg
Martin H
MH
Hale
Clarence
C
Hsieh
Feng-Yin
FY
Kelly
Michael G
MG
Liu
Qingyian
Q
Norman
Mark H
MH
Smith
Duncan M
DM
Stec
Markian
M
Tamayo
Nuria
N
Xi
Ning
N
Xu
Shimin
S
Bannon
Anthony W
AW
Baumgartner
James W
JW
D000818:Animals; D001667:Binding, Competitive; D005247:Feeding Behavior / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4; D013449:Sulfonamides