Optimization of piperazinebenzylamines with a N-(1-methoxy-2-propyl) side chain as potent and selective antagonists of the human melanocortin-4 receptor

Joseph Pontillo; Dragan Marinkovic; Joe A Tran; Melissa Arellano; Beth A Fleck; Jenny Wen; Fabio C Tucci; Jodie Nelson; John Saunders; Alan C Foster; Chen Chen

doi:10.1016/j.bmcl.2005.06.058

Optimization of piperazinebenzylamines with a N-(1-methoxy-2-propyl) side chain as potent and selective antagonists of the human melanocortin-4 receptor

Bioorg Med Chem Lett. 2005 Oct 15;15(20):4615-8. doi: 10.1016/j.bmcl.2005.06.058.

Authors

Joseph Pontillo¹, Dragan Marinkovic, Joe A Tran, Melissa Arellano, Beth A Fleck, Jenny Wen, Fabio C Tucci, Jodie Nelson, John Saunders, Alan C Foster, Chen Chen

Affiliation

¹ Department of Medicinal Chemistry, Neurocrine Biosciences Inc., 12790 El Camino Real, San Diego, CA 92130, USA.

PMID: 16105734
DOI: 10.1016/j.bmcl.2005.06.058

Abstract

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.

MeSH terms

Administration, Oral
Animals
Benzylamines / administration & dosage
Benzylamines / chemistry
Benzylamines / pharmacokinetics
Benzylamines / pharmacology*
Biological Availability
Cell Line
Humans
Mice
Piperazines / chemistry
Receptor, Melanocortin, Type 4 / antagonists & inhibitors*

Substances

Benzylamines
Piperazines
Receptor, Melanocortin, Type 4