Identification of novel β-lactams and pyrrolidinone derivatives as selective Histamine-3 receptor (H3R) modulators as possible anti-obesity agents.

Four series of structurally related β-lactams, 2,5-pyrrolidinediones, azaspirodecatrienediones (ASDT) and dihydropyrroloquinoxalinetriones (DPQT) were synthesized by utilizing post-Ugi modifications in one-pot, and their activity towards human histamine-3 receptor (H3R) was evaluated. Out of 94 compounds, screened against histamine-3 receptor (H3R), 21 compounds showed high H3R selective agonist property with EC values ranging from 187 nM to 0.1 nM, whereas none of the compound was found to have the affinity towards other receptors of histamine family such as histamine H1, H2, and H4 receptor.

Synthesis of Alkaloid-Mimicking Tricyclic Skeletons by Diastereo- and Regioselective Ugi/ipso-Cyclization/Aza-Michael Cascade Reaction in One-Pot.

A one-pot process has been developed for preparing alkaloid-like tricyclic skeletons by employing an Ugi reaction, an acid mediated ipso-cyclization and an aza-Michael addition. The transformation is operationally simple and provides products in a diastereo- and regioselective manner with good-to-excellent yields.