Identification of Ligand Binding Hot Spots of the Histamine H1 Receptor following Structure-Based Fragment Optimization was written by Kuhne, Sebastiaan;Kooistra, Albert J.;Bosma, Reggie;Bortolato, Andrea;Wijtmans, Maikel;Vischer, Henry F.;Mason, Jonathan S.;de Graaf, Chris;de Esch, Iwan J. P.;Leurs, Rob. And the article was included in Journal of Medicinal Chemistry in 2016.Quality Control of tert-Butyl 5,6-dihydropyridine-1(2H)-carboxylate This article mentions the following:
Developments in G protein-coupled receptor (GPCR) structural biol. provide insights into GPCR-ligand binding. Compound I (4-(2-benzylphenoxy)piperidine) with high ligand efficiency for the histamine H1 receptor (H1R) was used to design derivatives to investigate the roles of: (1) the amine-binding region, (2) the upper and lower aromatic region and (3) binding site solvation. SAR anal. showed that the amine-binding region serves as the primary binding hot spot, preferably binding small tertiary amines. In silico prediction of water network energetics and mutagenesis studies indicated that the displacement of a water mol. from the amine-binding region is most likely responsible for the increased affinity of the N-methylated analog of I. Deconstruction of I showed that the lower aromatic region serves as a secondary binding hot spot. This study demonstrates that an x-ray structure in combination with tool compounds, assessment of water energetics, and mutagenesis studies enables SAR exploration to map GPCR-ligand binding hot spots. In the experiment, the researchers used many compounds, for example, tert-Butyl 5,6-dihydropyridine-1(2H)-carboxylate (cas: 85838-94-4Quality Control of tert-Butyl 5,6-dihydropyridine-1(2H)-carboxylate).
tert-Butyl 5,6-dihydropyridine-1(2H)-carboxylate (cas: 85838-94-4) belongs to pyridine derivatives. Pyridines are an important class of heterocycles and occur in polysubstituted forms in many naturally occurring biologically active compounds, drug molecules and chiral ligands. Pyridine, its benzo and pyridine-based compounds play diverse roles in organic chemistry. Pyridine-based materials are valued for their optical and physical properties as well as their medical potential. Quality Control of tert-Butyl 5,6-dihydropyridine-1(2H)-carboxylate