Design and synthesis of 3-arylpyrrolidine-2-carboxamide derivatives as melanocortin-4 receptor ligands

Joe A Tran; Fabio C Tucci; Melissa Arellano; Wanlong Jiang; Caroline W Chen; Dragan Marinkovic; Beth A Fleck; Jenny Wen; Alan C Foster; Chen Chen

doi:10.1016/j.bmcl.2008.01.125

Design and synthesis of 3-arylpyrrolidine-2-carboxamide derivatives as melanocortin-4 receptor ligands

Bioorg Med Chem Lett. 2008 Mar 15;18(6):1931-8. doi: 10.1016/j.bmcl.2008.01.125. Epub 2008 Feb 7.

Authors

Joe A Tran¹, Fabio C Tucci, Melissa Arellano, Wanlong Jiang, Caroline W Chen, Dragan Marinkovic, Beth A Fleck, Jenny Wen, Alan C Foster, Chen Chen

Affiliation

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

PMID: 18294847
DOI: 10.1016/j.bmcl.2008.01.125

Abstract

Based on 3-phenylpropionamides, a series of 3-arylpyrrolidine-2-carboxamide derivatives was designed and synthesized to study the effect of cyclizations as melanocortin-4 receptor ligands. It was found that the 2R,3R-pyrrolidine isomer possessed the most potent affinity among the four stereoisomers.

MeSH terms

Administration, Oral
Animals
Biological Availability
Brain / drug effects
Cyclization
Drug Design*
Molecular Structure
Pyrrolidines / chemical synthesis*
Pyrrolidines / chemistry
Pyrrolidines / pharmacokinetics
Pyrrolidines / pharmacology
Rats
Receptor, Melanocortin, Type 4 / agonists*
Receptor, Melanocortin, Type 4 / metabolism
Stereoisomerism
Structure-Activity Relationship

Substances

Pyrrolidines
Receptor, Melanocortin, Type 4