Optimization of privileged structures for selective and potent melanocortin subtype-4 receptor ligands

Qingmei Hong; Raman K Bakshi; James Dellureficio; Shuwen He; Zhixiong Ye; Peter H Dobbelaar; Iyassu K Sebhat; Liangqin Guo; Jian Liu; Tianying Jian; Rui Tang; Rubana N Kalyani; Tanya Macneil; Aurawan Vongs; Charles I Rosenblum; David H Weinberg; Qingping Peng; Constantin Tamvakopoulos; Randy R Miller; Ralph A Stearns; Doreen Cashen; Willian J Martin; Airu S Chen; Joseph M Metzger; Howard Y Chen; Allison M Strack; Tung M Fong; Euan Maclntyre; Lex H T Van der Ploeg; Matthew J Wyvratt; Ravi P Nargund

doi:10.1016/j.bmcl.2010.06.038

Optimization of privileged structures for selective and potent melanocortin subtype-4 receptor ligands

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4483-6. doi: 10.1016/j.bmcl.2010.06.038. Epub 2010 Jun 10.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. [email protected]

PMID: 20598533
DOI: 10.1016/j.bmcl.2010.06.038

Abstract

Design, syntheses and structure-activity relationships of N-acetylated piperazine privileged structures containing MC4R agonist compounds were described. The most potent derivatives were low nM MC4R selective full agonists. Several compounds from the series had modest pharmacokinetic properties.

MeSH terms

Animals
Humans
Ligands*
Piperazine
Piperazines / chemical synthesis
Piperazines / chemistry
Piperazines / pharmacokinetics
Rats
Rats, Sprague-Dawley
Receptor, Melanocortin, Type 4 / agonists*
Receptor, Melanocortin, Type 4 / metabolism
Structure-Activity Relationship

Substances

Ligands
Piperazines
Receptor, Melanocortin, Type 4
Piperazine