Open AccessBIM-46174 fragments as potential ligands of G proteins
Author(s) -
Jim Küppers,
Tobias Benkel,
Suvi Annala,
Gregor Schnakenburg,
Evi Kostenis,
Michael Gütschow
Publication year - 2019
Publication title -
medchemcomm
Language(s) - English
Resource type - Journals
eISSN - 2040-2511
pISSN - 2040-2503
DOI - 10.1039/c9md00269c
Subject(s) - pharmacophore , pyrazine , diazepine , bicyclic molecule , chemical space , derivative (finance) , chemistry , stereochemistry , combinatorial chemistry , ring (chemistry) , biochemistry , drug discovery , organic chemistry , financial economics , economics
The 5,6,7,8-tetrahydroimidazo[1,2- a ]pyrazine derivative BIM-46174 has received attention as Gα q 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 Gα q 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 Gα q inhibition.