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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiotensin II / metabolism*
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Angiotensin Receptor Antagonists
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Antihypertensive Agents / chemistry*
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Antihypertensive Agents / pharmacology
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Biphenyl Compounds / chemistry*
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Biphenyl Compounds / pharmacology
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Crystallography, X-Ray
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Humans
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Irbesartan
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Models, Molecular
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Pyrazoles / chemistry*
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Pyrazoles / pharmacology
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Pyridazines / chemistry*
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Pyridazines / pharmacology
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Receptor, Angiotensin, Type 1
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Receptors, Angiotensin / chemistry*
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Receptors, Angiotensin / metabolism
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Structure-Activity Relationship
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Tetrazoles / chemistry*
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Tetrazoles / pharmacology
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Tumor Cells, Cultured
Substances
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Angiotensin Receptor Antagonists
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Antihypertensive Agents
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Biphenyl Compounds
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Pyrazoles
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Pyridazines
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Receptor, Angiotensin, Type 1
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Receptors, Angiotensin
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Tetrazoles
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Angiotensin II
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Irbesartan