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.
Subject(s)
Benzamidines/chemical synthesis , Emaciation/drug therapy , Imidazoles/chemical synthesis , Neoplasms/complications , Receptor, Melanocortin, Type 4/antagonists & inhibitors , Administration, Cutaneous , Animals , Benzamidines/chemistry , Benzamidines/pharmacology , Emaciation/etiology , Imidazoles/chemistry , Imidazoles/pharmacology , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Radioligand Assay , Structure-Activity Relationship , Transplantation, HeterologousABSTRACT
Novel substituted 2-anilino- and 2-cycloalkylaminoquinoxalines have been found to be useful and selective inhibitors of PDGF-R autophosphorylation. Replacement of an anilino-substituent with substituted cyclohexylamino- or norbornylamino substituents led to significant improvements in the pharmacokinetic profile of these analogues.
