Wagner, Gabor published the artcileCovalent inhibition of the histamine Hi3 receptor, Category: pyrimidines, the main research area is histamine covalent inhibition receptor; G protein-coupled receptor (GPCR); Histamine H3 receptor; covalent binder; isothiocyanate.
Covalent binding of G protein-coupled receptors by small mols. is a useful approach for better understanding of the structure and function of these proteins. We designed, synthesized and characterized a series of 6 potential covalent ligands for the histamine Hi3 receptor (Hi3R). Starting from a 2-amino-pyrimidine scaffold, optimization of anchor moiety and warhead followed by fine-tuning of the required reactivity via scaffold hopping resulted in the isothiocyanate Hi3R ligand 44. It shows high reactivity toward glutathione combined with appropriate stability in water and reacts selectively with the cysteine sidechain in a model nonapeptide equipped with nucleophilic residues. The covalent interaction of 44 with Hi3R was validated with washout experiments and leads to inverse agonism on Hi3R. Irreversible binder 44 (VUF15662) may serve as a useful tool compound to stabilize the inactive Hi3R conformation and to study the consequences of prolonged inhibition of the Hi3R.
Molecules published new progress about Histamine H3 receptor agonists Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 73576-33-7 belongs to class pyrimidines, name is 4-Chloro-6-isopropylpyrimidin-2-amine, and the molecular formula is C7H10ClN3, Category: pyrimidines.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia