Abstract
A novel series of 6-alkyl-7-oxo-4,7-dihydropyrazolo[1,5-alpha]pyrimidine-3-carboxyli c acid derivatives was prepared as angiotensin II (AII) receptor antagonists. When evaluated in an in vitro binding assay using COS cells transfected with a cDNA encoding a human AT1 angiotensin II receptor, the compounds in this series showed Ki values in the range of 0.4-4.0 nM. In anesthetized spontaneously hypertensive rats (SHRs), administration of the 6-propyl derivative 4d (1 mg/kg, i.v.) reduced the mean blood pressure (MBP) by a maximum of more than 30 mmHg from the normal value.
MeSH terms
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Angiotensin II / metabolism*
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Angiotensin Receptor Antagonists*
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Animals
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Antihypertensive Agents / chemical synthesis
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Antihypertensive Agents / pharmacology
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Blood Pressure / drug effects
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Cell Line
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Chemical Phenomena
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Chemistry, Physical
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Humans
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In Vitro Techniques
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Kinetics
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Liver / drug effects
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Liver / metabolism
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Pyrazoles / chemical synthesis*
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Pyrazoles / pharmacology
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Pyrimidines / chemical synthesis*
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Pyrimidines / pharmacology
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Rats
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Rats, Inbred SHR
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Receptors, Angiotensin / biosynthesis
Substances
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Angiotensin Receptor Antagonists
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Antihypertensive Agents
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Pyrazoles
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Pyrimidines
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Receptors, Angiotensin
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Angiotensin II