Carpino Philip A, Griffith David A, Sakya Subas, Dow Robert L, Black Shawn C, Hadcock John R, Iredale Philip A, Scott Dennis O, Fichtner Michael W, Rose Colin R, Day Robert, Dibrino Joseph, Butler Mary, Debartolo Demetria B, Dutcher Darrin, Gautreau Denise, Lizano Jeff S, O'connor Rebecca E, Sands Michelle A, Kelly-Sullivan Dawn, Ward Karen M
Pfizer Global Research and Development-Groton Laboratories, Groton, CT 06340, USA.
Bioorg Med Chem Lett. 2006 Feb;16(3):731-6. doi: 10.1016/j.bmcl.2005.10.019. Epub 2005 Nov 2.
A series of conformationally constrained bicyclic derivatives derived from SR141716 was prepared and evaluated as hCB(1)-R antagonists and inverse agonists. Optimization of the structure-activity relationships around the 2,6-dihydro-pyrazolo[4,3-d]pyrimidin-7-one derivative 2a led to the identification of two compounds with oral activity in rodent feeding models (2h and 4a). Replacement of the PP group in 2h with other bicyclic groups resulted in a loss of binding affinity.
