Optimization of piperazinebenzylamines with a N-(1-methoxy-2-propyl) side chain as potent and selective antagonists of the human melanocortin-4 receptor.
Piperazinebenzylamines bearing a small N-(1-methoxy-2-propyl) side chain were found to be potent and selective antagonists of the human melanocortin-4 (MC4) receptor. Compound 7b, having K(i) values of 6.9 and 2800 nM at the human MC4 and MC3 receptors, respectively, has moderate oral bioavailability in mice, which is improved relative to the arylethyl analogues.
Pontillo
Joseph
J
Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA.
Marinkovic
Dragan
D
Tran
Joe A
JA
Arellano
Melissa
M
Fleck
Beth A
BA
Wen
Jenny
J
Tucci
Fabio C
FC
Nelson
Jodie
J
Saunders
John
J
Foster
Alan C
AC
Chen
Chen
C
D000284:Administration, Oral; D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D001682:Biological Availability; D002460:Cell Line; D006801:Humans; D051379:Mice; D010879:Piperazines / Q000737:chemistry; D044105:Receptor, Melanocortin, Type 4 / Q000037:antagonists & inhibitors*
D001596:Benzylamines; D010879:Piperazines; D044105:Receptor, Melanocortin, Type 4