Identification of 2-[2-[2-(5-bromo-2- methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model

Tricia J Vos; Andrei Caracoti; Jennifer L Che; Mingshi Dai; Cheryl A Farrer; Nancy E Forsyth; Stacey V Drabic; Robert A Horlick; Diana Lamppu; David L Yowe; Suresh Balani; Ping Li; Hang Zeng; Ingrid B J K Joseph; Luis E Rodriguez; Martin P Maguire; Michael A Patane; Christopher F Claiborne

doi:10.1021/jm034244g

Identification of 2-[2-[2-(5-bromo-2- methoxyphenyl)-ethyl]-3-fluorophenyl]-4,5-dihydro-1H-imidazole (ML00253764), a small molecule melanocortin 4 receptor antagonist that effectively reduces tumor-induced weight loss in a mouse model

J Med Chem. 2004 Mar 25;47(7):1602-4. doi: 10.1021/jm034244g.

Authors

Tricia J Vos¹, Andrei Caracoti, Jennifer L Che, Mingshi Dai, Cheryl A Farrer, Nancy E Forsyth, Stacey V Drabic, Robert A Horlick, Diana Lamppu, David L Yowe, Suresh Balani, Ping Li, Hang Zeng, Ingrid B J K Joseph, Luis E Rodriguez, Martin P Maguire, Michael A Patane, Christopher F Claiborne

Affiliation

¹ Department of Medicinal Chemistry, Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, Massachusetts 02139, USA. tricia.vos@mpi.com

PMID: 15027849
DOI: 10.1021/jm034244g

Abstract

The melanocortin 4 receptor (MC4R) plays an important role in body weight regulation and energy homeostasis. Administration of peptidic MC4R antagonists (usually by intracerebro ventricular injection) has been shown in the literature to increase body weight and/or food intake in several rodent models. We report here the identification of a novel nonpeptidic MC4R antagonist and its effects on tumor-induced weight loss in mice following peripheral administration.

MeSH terms

Administration, Cutaneous
Animals
Benzamidines / chemical synthesis*
Benzamidines / chemistry
Benzamidines / pharmacology
Emaciation / drug therapy*
Emaciation / etiology
Imidazoles / chemical synthesis*
Imidazoles / chemistry
Imidazoles / pharmacology
Mice
Mice, Inbred BALB C
Neoplasm Transplantation
Neoplasms / complications*
Radioligand Assay
Receptor, Melanocortin, Type 4 / antagonists & inhibitors*
Structure-Activity Relationship
Transplantation, Heterologous

Substances

2-(2-(2-(5-bromo-2-methoxyphenyl)ethyl)-3-fluorophenyl)-4,5-dihydro-1H-imidazole
Benzamidines
Imidazoles
Receptor, Melanocortin, Type 4