878744-25-3Relevant academic research and scientific papers
Structure-Based Design, Synthesis, and Biological Evaluation of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors
Waldschmidt, Helen V.,Homan, Kristoff T.,Cruz-Rodríguez, Osvaldo,Cato, Marilyn C.,Waninger-Saroni, Jessica,Larimore, Kelly M.,Cannavo, Alessandro,Song, Jianliang,Cheung, Joseph Y.,Kirchhoff, Paul D.,Koch, Walter J.,Tesmer, John J. G.,Larsen, Scott D.
, p. 3793 - 3807 (2016)
G protein-coupled receptors (GPCRs) are central to many physiological processes. Regulation of this superfamily of receptors is controlled by GPCR kinases (GRKs), some of which have been implicated in heart failure. GSK180736A, developed as a Rho-associated coiled-coil kinase 1 (ROCK1) inhibitor, was identified as an inhibitor of GRK2 and co-crystallized in the active site. Guided by its binding pose overlaid with the binding pose of a known potent GRK2 inhibitor, Takeda103A, a library of hybrid inhibitors was developed. This campaign produced several compounds possessing high potency and selectivity for GRK2 over other GRK subfamilies, PKA, and ROCK1. The most selective compound, 12n (CCG-224406), had an IC50 for GRK2 of 130 nM, >700-fold selectivity over other GRK subfamilies, and no detectable inhibition of ROCK1. Four of the new inhibitors were crystallized with GRK2 to give molecular insights into the binding and kinase selectivity of this class of inhibitors.
WDR5 INHIBITORS AND MODULATORS
-
Paragraph 0179; 0919, (2020/04/24)
Described are imino-azacycle-benzamide compounds compounds that inhibit WDR5 and associated protein-protein interactions, pharmaceutical compositions including the compounds, and methods of using the compounds and compositions for treating disorders and c
G PROTEIN-COUPLED RECEPTOR KINASE 2 INHIBITORS AND METHODS FOR USE OF THE SAME
-
, (2016/03/19)
Disclosed herein are novel GRK2 inhibitors and methods for their use in treating or preventing heart disease, such as cardiac failure, cardiac hypertrophy, and hypertension. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically
BIPHENYL CARBOXYLIC ACIDS AND BIOISOSTERES AS GLYCOGEN SYNTHASE ACTIVATORS
-
, (2011/06/10)
Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful
NOVEL CARBOXYLIC ACID ANALOGS AS GLYCOGEN SYNTHASE ACTIVATORS
-
, (2011/06/24)
Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of metabolic diseases and disorders such as, for example, type II diabetes mellitus.
QUINAZOLINONE DERIVATIVES AND THEIR USE AS B-RAF INHIBITORS
-
Page/Page column 81-82, (2008/06/13)
The invention relates to chemical compounds of the formula (I): or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
QUINOXALINES AS B RAF INHIBITORS
-
Page/Page column 62, (2010/11/08)
The invention relates to chemical compounds of the formula (I) or pharmaceutically acceptable salts thereof, which possess B Raf inhibitory activity and are accordingly useful for their anti cancer activity and thus in methods of treatment of the human or animal body. The invention also relates to processes for the manufacture of said chemical compounds, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments of use in the production of an anti-cancer effect in a warm blooded animal such as man.
