Synthesis of Tetrahydrocarbazole Derivatives as Potent beta_3-Adrenoceptor Agonists

摘要

A series of 2-(3-chlorophenyl)-2-hydroxyethylamine derivatives containing a tetrahydrocarbazole linker were prepared and evaluated for their beta_3-adrenoceptor agonistic activity.Several compounds showed potency comparable to CL-316243.As a subclass of beta-adrenoceptors,beta_3-adrenoceptor(beta_3-AR)is found on the cell surface of both white and brown adipocytes and mediates various metabolic processes such as lipolysis and thermogenesis.Activation of human beta_3-AR results in an increase of c-AMP level in adipocytes,leading to an elevation of metabolic rate.Therefore,discovery of a human beta_3-AR agonist would be an attractive approach to the treatment of human disease states,such as obesity and type II diabetes.