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 the artcile< N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands>, Product Details of C7H12N2, the main research area is AT2 receptor ligand thiophene sulfonamide; AT(2)R ligands; Angiotensin II type 2 receptor; Carboxylic acid bioisosteres; Liver microsomes; Sulfonyl carbamates.
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.
Bioorganic & Medicinal Chemistry published new progress about Angiotensin AT1 receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 36947-69-0 belongs to class imidazoles-derivatives, and the molecular formula is C7H12N2, Product Details of C7H12N2.
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem