Tetrahydroimidazo[1,2-a]pyrazine Derivatives: Synthesis and Evaluation as Gα_q -Protein Ligands.

ABSTRACT: The 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine derivative BIM-46174 and its dimeric form BIM-46187 (1) are heterocyclized dipeptides that belong to the very few cell-permeable compounds known to preferentially silence Gα_q proteins. To explore the chemical space of Gα_q inhibitors of the BIM chemotype, a combinatorial approach was conducted towards a library of BIM molecules. This library was evaluated in a second messenger-based fluorescence assay to analyze the activity of Gα_q proteins through the determination of intracellular myo-inositol 1-phosphate. Structure-activity relationships were deduced and structural requirements for biological activity obtained, which were (i) a redox reactive thiol/disulfane substructure, (ii) an N-terminal basic amino group, (

SUBMITTER: Kuppers J 

PROVIDER: S-EPMC7590114 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature