Wannberg, Johan; Gising, Johan; Lindman, Jens; Salander, Jessica; Gutierrez-de-Teran, Hugo; Ablahad, Hanin; Hamid, Selin; Groenbladh, Alfhild; Spizzo, Iresha; Gaspari, Tracey A.; Widdop, Robert E.; Hallberg, Anders; Backlund, Maria; Lesniak, Anna; Hallberg, Mathias; Larhed, Mats published their research in Bioorganic & Medicinal Chemistry in 2021. The article was titled 《N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands》.Application In Synthesis of 2-Bromo-1H-imidazole The article contains the following contents:
A series of meta-substituted acetophenone derivatives, encompassing N-(alkyloxycarbonyl)thiophene sulfonamide fragments have been synthesized. Several selective AT2 receptor ligands were identified, among those a tert-butylimidazole derivative (20) with a Ki of 9.3 nM, that demonstrates a high stability in human liver microsomes (t1/2 = 62 min) and in human hepatocytes (t1/2 = 194 min). This methyloxycarbonylthiophene sulfonamide is a 20-fold more potent binder to the AT2 receptor and is considerably more stable in human liver microsomes, than a previously reported and broadly studied structurally related AT2R prototype antagonist 3 (C38). Ligand 20 acts as an AT2R agonist and caused an AT2R mediated concentration-dependent vasorelaxation of pre-contracted mouse aorta. Furthermore, in contrast to imidazole derivative C38, the tert-butylimidazole derivative 20 is a poor inhibitor of CYP3A4, CYP2D6 and CYP2C9. It is demonstrated herein that smaller alkyloxycarbonyl groups make the ligands in this series of AT2R selective compounds less prone to degradation and that a high AT2 receptor affinity can be retained after truncation of the alkyloxycarbonyl group. Binding modes of the most potent AT2R ligands were explored by docking calculations combined with mol. dynamics simulations. In the part of experimental materials, we found many familiar compounds, such as 2-Bromo-1H-imidazole(cas: 16681-56-4Application In Synthesis of 2-Bromo-1H-imidazole)
2-Bromo-1H-imidazole(cas: 16681-56-4) is a member of imidazole. Its exclusive structural characteristics with enviable electron-rich features are favorable for imidazole-based fused heterocycles to bind efficiently with an array of enzymes and receptors in biological systems through various weak interactions like hydrogen bonds, ion-dipole, cation-π, π-π stacking, coordination, Van der Waals forces, hydrophobic effects, etc., and therefore they demonstrate widespread bioactivities. Application In Synthesis of 2-Bromo-1H-imidazole
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem