Author/Authors :
Joseph Pontillo، نويسنده , , Joseph A. Tran، نويسنده , , Stacy Markison، نويسنده , , Margaret Joppa، نويسنده , , Beth A. Fleck، نويسنده , , Dragan Marinkovic، نويسنده , , Melissa Arellano، نويسنده , , Fabio C. Tucci، نويسنده , , Marion Lanier، نويسنده , , Jodie Nelson، نويسنده , , John Saunders، نويسنده , , Sam R.J. Hoare، نويسنده , , Alan C. Foster، نويسنده , , Chen Chen، نويسنده ,
Abstract :
Optimization on a series of piperazinebenzylamines resulted in analogues with low nanomolar binding at the human MC4 receptor but weak affinity (Ki > 500 nM) at the MC3 receptor. Compound 14c was identified to be a potent MC4R antagonist (Ki = 3.2 nM) with a selectivity of 240-fold over MC3R. It proved to be an insurmountable antagonist in a cAMP assay. Compound 14c potently stimulated food intake in satiated mice when given by intracerebroventricular administration.
Keywords :
Melanocortin-4 , Antagonist , Piperazinebenzylamine , food intake
