Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands

Molecules

Loredana Salerno¹  Agostino Marrazzo¹  Giuseppe Romeo¹  Sebastiano Intagliata¹  MariaN. Modica¹  Luisa Materia¹  Valeria Pittal๠ Mario Salmona²  Alfredo Cagnotto²  MohamedA. Helal³ 

[1] Department of Drug Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy;Istituto di Ricerche Farmacologiche “Mario Negri”, IRCCS. Via Mario Negri, 2, 20156 Milano, Italy;University of Science and Technology, Biomedical Sciences Program, Zewail City of Science and Technology, October Gardens, 6th of October, Giza 12578, Egypt;

关键词: endothelin receptors;    ET_A ligands;    1,3-diaryl-5-oxo-proline derivatives;    homology modeling;    molecular docking;   

DOI  :  10.3390/molecules25081851

来源: DOAJ

【 摘 要 】

The synthesis of seventeen new 1,3-diaryl-5-oxo-proline derivatives as endothelin receptor (ETR) ligands is described. The structural configuration of the new molecules was determined by analyzing selected signals in proton NMR spectra. In vitro binding assays of the human ET_A and ET_B receptors allowed us to identify compound 31h as a selective ET_AR ligand. The molecular docking of the selected compounds and the ET_A antagonist atrasentan in the ET_AR homology model provided insight into the structural elements required for the affinity and the selectivity of the ET_AR subtype.

【 授权许可】

Unknown