title: Comparison of 3D structures and AT(1) binding properties of pyrazolidine-3,5-diones and tetrahydropyridazine-3,6-diones with parent antihypertensive drug irbesartan.
abstract: A new series of nonpeptide AT(1) receptor antagonists were recently developed, based on the structure of irbesartan (Le Bourdonnec et al. J. Med. Chem. 2000, 43, 2685-2697). The lead compound 1 displayed high selectivity for the AT(1) receptor subtype but lower binding affinity than irbesartan. As expected from molecular modeling studies, extension of the pyrazolidine-3,5-dione scaffold to the six-membered heterocycle tetrahydropyridazine-3,6-dione led to an enhancement of the binding affinity toward the AT(1) receptor.
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000737:chemistry* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D006801:Humans; D000077405:Irbesartan; D008958:Models, Molecular; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology; D011724:Pyridazines / Q000737:chemistry* / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D011720:Pyrazoles; D011724:Pyridazines; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D000077405:Irbesartan