Privileged structure based ligands for melanocortin receptors--substituted benzylic piperazine derivatives.
Replacement of the aryl piperazine moiety in compound 1 with a variety of substituted benzylic piperazines (6) yields compounds that afford melanocortin receptor 4 (MCR4) activity. Analogs with ortho substitution on the aromatic ring afforded the highest affinity. Resolution of the stereocenter of the benzylic piperazine based privileged structure revealed that the R-enantiomer was more active.
Fisher
Matthew J
MJ
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46258, USA. fisher_matthew_j@lilly.com
Backer
Ryan T
RT
Collado
Iván
I
de Frutos
Oscar
O
Husain
Saba
S
Hsiung
Hansen M
HM
Kuklish
Steve L
SL
Mateo
Ana I
AI
Mullaney
Jeffrey T
JT
Ornstein
Paul L
PL
Paredes
Cristina García
CG
O'Brian
Thomas P
TP
Richardson
Timothy I
TI
Shah
Jikesh
J
Zgombick
John M
JM
Briner
Karin
K
D001555:Benzene Derivatives / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism*; D044101:Receptors, Melanocortin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
D001555:Benzene Derivatives; D008024:Ligands; D010879:Piperazines; D044101:Receptors, Melanocortin; D000077489:Piperazine