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Updated: Dec 26, 2025

Measuring G-protein-coupled Receptor Signaling via Radio-labeled GTP Binding
Published on: June 9, 2017
BIM-46174 fragments as potential ligands of G proteins
Jim Küppers1, Tobias Benkel2,3, Suvi Annala2
1Pharmaceutical Institute , Pharmaceutical Chemistry I , University of Bonn , An der Immenburg 4 , 53121 Bonn , Germany .
Abstract:
The 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine derivative BIM-46174 has received attention as Gαq inhibitor. We conducted structural reductions to monocyclic and bicyclic substructures to explore the chemical space of BIM fragments and to gain insights into the pharmacophore of BIM-type Gαq inhibitors. Two piperazin-2-one-containing fragments and a small library of bicyclic lactams featuring fused pyrazine and diazepine rings were synthesized and evaluated. The results of a second messenger-based cellular assay indicate that the entire BIM structure is required for efficient Gαq inhibition.
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