Structure-activity relationship studies on a series of piperazinebenzylalcohols and their ketone and amine analogs as melanocortin-4 receptor ligands

Dragan Marinkovic; Fabio C Tucci; Joe A Tran; Beth A Fleck; Jenny Wen; Chen Chen

doi:10.1016/j.bmcl.2008.07.076

Structure-activity relationship studies on a series of piperazinebenzylalcohols and their ketone and amine analogs as melanocortin-4 receptor ligands

Bioorg Med Chem Lett. 2008 Sep 1;18(17):4817-22. doi: 10.1016/j.bmcl.2008.07.076. Epub 2008 Jul 25.

Authors

Dragan Marinkovic¹, Fabio C Tucci, Joe A Tran, Beth A Fleck, Jenny Wen, Chen Chen

Affiliation

¹ Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., 12790 El Camino Real, San Diego, CA 92121, USA.

PMID: 18682322
DOI: 10.1016/j.bmcl.2008.07.076

Abstract

A series of piperazinebenzylalcohols were prepared and studied to compare with their ketone and amine analogs as MC4R antagonists. Several benzylalcohols such as 14a and 14g displayed low nanomolar binding affinities (K(i)<10 nM), and high selectivities over other melanocortin receptor subtypes.

Publication types

Comparative Study

MeSH terms

Amines / chemical synthesis
Amines / chemistry
Amines / metabolism*
Amino Acid Substitution
Animals
Benzyl Alcohols / chemical synthesis
Benzyl Alcohols / chemistry
Benzyl Alcohols / metabolism*
Binding, Competitive
Cell Line
Humans
Ketones / chemical synthesis
Ketones / chemistry
Ketones / metabolism*
Ligands
Melanocortins / antagonists & inhibitors
Melanocortins / metabolism
Piperazines / chemical synthesis
Piperazines / chemistry
Piperazines / metabolism*
Protein Binding
Rats
Receptor, Melanocortin, Type 4 / chemistry
Receptor, Melanocortin, Type 4 / metabolism*
Structure-Activity Relationship

Substances

Amines
Benzyl Alcohols
Ketones
Ligands
Melanocortins
Piperazines
Receptor, Melanocortin, Type 4