2) Negative Allosteric Modulators (NAMs) Based on Functionalized Pyrazolo[1,5-a]pyrimidine-5-carboxamide and Thieno[3,2-b]pyridine-]]>

摘要

A scaffold hopping exercise from a monocyclic mGlu_(2) NAM with poor rodent PK led to two novel heterobicyclic series of mGlu_(2) NAMs based on either a functionalized pyrazolo[1,5-a ]pyrimidine-5-carboxamide core or a thieno[3,2-b ]pyridine-5-carboxamide core. These novel analogues possess enhanced rodent PK, while also maintaining good mGlu_(2) NAM potency, selectivity (versus mGlu_(3) and the remaining six mGlu receptors), and high CNS penetration. Interestingly, SAR was divergent between the new 5,6-heterobicyclic systems.