Discovery of a piperazine urea based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist

Qingmei Hong; Raman K Bakshi; Brenda L Palucki; Min K Park; Zhixiong Ye; Shuwen He; Patrick G Pollard; Iyassu K Sebhat; Jian Liu; Liangqin Guo; Doreen E Cashen; William J Martin; David H Weinberg; Tanya MacNeil; Rui Tang; Constantin Tamvakopoulos; Qianping Peng; Randy R Miller; Ralph A Stearns; Howard Y Chen; Airu S Chen; Alison M Strack; Tung M Fong; D Euan MacIntyre; Matthew J Wyvratt; Ravi P Nargund

doi:10.1016/j.bmcl.2011.02.090

Discovery of a piperazine urea based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2330-4. doi: 10.1016/j.bmcl.2011.02.090. Epub 2011 Mar 1.

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. Qingmei_hong@merck.com

PMID: 21439820
DOI: 10.1016/j.bmcl.2011.02.090

Abstract

We report the discovery of piperazine urea based compound 1, a potent, selective, orally bioavailable melanocortin subtype-4 receptor partial agonist. Compound 1 shows anti-obesity efficacy without potentiating erectile activity in the rodent models.

MeSH terms

Administration, Oral
Animals
Biological Availability
Disease Models, Animal
Dogs
Drug Evaluation, Preclinical
Eating / drug effects
Haplorhini
Mice
Obesity / drug therapy
Piperazines / chemistry*
Piperazines / pharmacokinetics
Piperazines / therapeutic use
Rats
Rats, Sprague-Dawley
Receptor, Melanocortin, Type 4 / agonists*
Receptor, Melanocortin, Type 4 / genetics
Receptor, Melanocortin, Type 4 / metabolism
Structure-Activity Relationship
Urea / analogs & derivatives*
Urea / chemistry
Urea / pharmacokinetics
Urea / therapeutic use

Substances

Piperazines
Receptor, Melanocortin, Type 4
Urea