Potent and orally bioavailable nonpeptidyl melanocortin subtype-4 receptor modulators: Syntheses, SAR and pharmacokinetics

MEDI 38

Liangqin Guo, liangqin_guo@merck.com1, Zhixiong Ye1, Iyassu K. Sebhat1, Feroze Ujjainwalla1, Heather L. Sings1, David H. Weinberg2, Rui Tang2, Tanya MacNeil2, Constantin Tamvakopoulos3, Qianping Peng3, Euan MacIntyre4, Lex H. T. Van der Ploeg5, Mark T. Goulet1, Matthew J. Wyvratt1, and Ravi P. Nargund, ravi_nargund@merck.com1. (1) Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 2000, RY 50G-332, Rahway, NJ 07065, (2) Department of Metabolic Disorders, Merck Research Laboratories, 126 E. Lincoln Avenue, P.O.Box 2000, Rahway, NJ 07065, (3) Department of Drug Metabolism, Merck Research Laboratories, 126 E. Lincoln Avenue, P.O.Box 2000, Rahway, NJ 07065, (4) Department of Pharmacology, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, (5) Department of Obesity Research, Merck & Co., Inc, PO Box, 2000, Rahway, NJ 07065
The melanocortin receptors are known as a family of five seven–transmembrane G-protein-coupled receptors. Of these five subtypes, the melanocortin-4 receptor (MC4R) has been clearly linked to the regulation of energy homeostasis and feeding regulation. Increasing efforts have been attracted to develop potent and selective non-peptide MC4R agonists. In this presentation, the synthesis, SAR and pharmacokinetics of a series of orally bioavailable, non-peptidyl, t-butyl pyrrolidine derived, potent and MC4R selective compounds will be discussed (Figure 1).

 

Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007