Cyclopenta[d]pyrimidines and dihydropyrrolo[2,3-d]pyrimidines as potent and selective corticotropin-releasing factor 1 receptor antagonists.

Two new classes of potent and selective CRF(1) receptor antagonists are presented. Exploration of general templates 3 and 4 through modifications of the top amine and bottom phenyl substituents led to optimization of the in vitro affinity and pharmacokinetic profiles. The typical alkyl chains present in the top region of CRF(1) antagonists were replaced by substituted heteroaryl moieties, leading to a dramatic improvement of the metabolic stability.

Diaryl substituted pyrrolidinones and pyrrolones as 5-HT2C inhibitors: synthesis and biological evaluation.

Within the continuous quest for the discovery of novel compounds able to treat anxiety and depression, the generation of a pharmacophore model for 5-HT2C receptor antagonists and the discovery of a new class of potent and selective 5-HT2C molecules are reported.