Privileged structure based ligands for melanocortin-4 receptors--aliphatic piperazine derivatives.
Aliphatic carbocyclic replacement of the benzyl group of compound 1 yielded compounds with high affinity for the melanocortin-4 receptor (MC4R). Compounds with a cyclohexyl group showed a consistent high affinity, while different polar groups with less basicity were good replacements for the original diethyl amines. Substitution of the polar group found in these privileged structures with an aliphatic moiety produced compounds with high affinity for MC4R.
Briner
Karin
K
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46258, USA.
Collado
Iván
I
Fisher
Matthew J
MJ
García-Paredes
Cristina
C
Husain
Saba
S
Kuklish
Steven L
SL
Mateo
Ana I
AI
O'Brien
Thomas P
TP
Ornstein
Paul L
PL
Zgombick
John
J
de Frutos
Oscar
O
D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D044105:Receptor, Melanocortin, Type 4 / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D008024:Ligands; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4