BIM-46174 fragments as potential ligands of G proteins. Issue 10 (30th August 2019)

• Record Type: Journal Article
• Authors: Küppers, Jim; Benkel, Tobias; Annala, Suvi; Schnakenburg, Gregor; Kostenis, Evi; Gütschow, Michael
• Is Part Of: MedChemComm. Volume 10:Issue 10(2019)
• Page Start: 1838
• Page End: 1843
• Publication Date: 2019-08-30
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c9md00269c
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Fragments of BIM-46174 were synthesized and investigated as Gαq inhibitors. 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.