Discovery of melanin-concentrating hormone receptor R1 antagonists using high-throughput synthesis

Jing Su; Brian A McKittrick; Haiqun Tang; Michael Czarniecki; William J Greenlee; Brian E Hawes; Kim O'Neill

doi:10.1016/j.bmc.2004.11.046

Discovery of melanin-concentrating hormone receptor R1 antagonists using high-throughput synthesis

Bioorg Med Chem. 2005 Mar 1;13(5):1829-36. doi: 10.1016/j.bmc.2004.11.046.

Authors

Jing Su¹, Brian A McKittrick, Haiqun Tang, Michael Czarniecki, William J Greenlee, Brian E Hawes, Kim O'Neill

Affiliation

¹ Department of Chemical Research, Schering-Plough Research Institute K15 2545, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. [email protected]

PMID: 15698800
DOI: 10.1016/j.bmc.2004.11.046

Abstract

A structure-activity study on benzylpiperidine 1 was accomplished by utilizing high-throughput synthesis. Three focused libraries were designed and synthesized to quickly develop SAR. Further optimization led to the discovery of compound 2, an MCH receptor R1 antagonist with over 400-fold improvement in biological activity over the original lead.

MeSH terms

Hormone Antagonists / chemical synthesis*
Hormone Antagonists / metabolism
Hormone Antagonists / pharmacology*
Magnetic Resonance Spectroscopy
Receptors, Pituitary Hormone / antagonists & inhibitors*
Receptors, Pituitary Hormone / metabolism
Structure-Activity Relationship

Substances

Hormone Antagonists
Receptors, Pituitary Hormone
melanin-concentrating hormone receptor