Title of article :
Constrained analogs of CB-1 antagonists: 1,5,6,7-Tetrahydro-4H-pyrrolo[3,2-c]pyridine-4-one derivatives
Author/Authors :
Roger A. Smith، نويسنده , , Zahra Fathi، نويسنده , , Su-Ellen Brown، نويسنده , , Soongyu Choi، نويسنده , , Jianmei Fan، نويسنده , , Susan Jenkins، نويسنده , , Harold C.E. Kluender، نويسنده , , Anish Konkar، نويسنده , , Rico Lavoie، نويسنده , , Ronald Mays، نويسنده , , Jennifer Natoli، نويسنده , , Stephen J. O’Connor، نويسنده , , Astrid A. Ortiz، نويسنده , , Brent Podlogar، نويسنده , , Christy Taing، نويسنده , , Susan Tomlinson، نويسنده , , Theresa Tritto، نويسنده , , Zhonghua Zhang، نويسنده ,
Abstract :
A series of pyrrolopyridinones was designed and synthesized as constrained analogs of the pyrazole CB-1 antagonist rimonabant. Certain examples exhibited very potent hCB-1 receptor binding affinity and functional antagonism with Ki and Kb values below 10 nM, and with high selectivity for CB-1 over CB-2 (>100-fold). A representative analog was established to cause significant appetite suppression and reduction in body weight gain in industry-standard rat models used to develop new therapeutics for obesity.
Keywords :
Cannabinoid , Antagonist , obesity , Appetite suppressant
