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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
1992-4-3
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pubmed:abstractText |
As part of a program to discover potent antihypertensive analogues of diltiazem (3a), we prepared 1-benzazepin-2-ones (4). Benzazepinones competitively displace radiolabeled diltiazem, and show the same absolute stereochemical preferences at the calcium channel receptor protein. Derivatives of 4 containing a trifluoromethyl substituent in the fused aromatic ring show potent and long-acting antihypertensive activity. Studies of the metabolism of 4 lead to the metabolically stable antihypertensive calcium channel blockers 5a and 5c. Benzazepinone 5a is a longer acting and more potent antihypertensive agent than the second generation diltiazem analogue TA-3090 (3e).
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
21
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
N
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pubmed:pagination |
756-72
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:1542102-Acetylation,
pubmed-meshheading:1542102-Animals,
pubmed-meshheading:1542102-Antihypertensive Agents,
pubmed-meshheading:1542102-Aorta,
pubmed-meshheading:1542102-Benzazepines,
pubmed-meshheading:1542102-Calcium Channel Blockers,
pubmed-meshheading:1542102-Diltiazem,
pubmed-meshheading:1542102-Guinea Pigs,
pubmed-meshheading:1542102-Hypertension,
pubmed-meshheading:1542102-Male,
pubmed-meshheading:1542102-Microsomes, Liver,
pubmed-meshheading:1542102-Molecular Conformation,
pubmed-meshheading:1542102-Molecular Structure,
pubmed-meshheading:1542102-Pyrrolidines,
pubmed-meshheading:1542102-Rabbits,
pubmed-meshheading:1542102-Rats,
pubmed-meshheading:1542102-Rats, Inbred SHR,
pubmed-meshheading:1542102-Structure-Activity Relationship,
pubmed-meshheading:1542102-Vasodilation
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pubmed:year |
1992
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pubmed:articleTitle |
Benzazepinone calcium channel blockers. 2. Structure-activity and drug metabolism studies leading to potent antihypertensive agents. Comparison with benzothiazepinones.
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pubmed:affiliation |
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
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pubmed:publicationType |
Journal Article,
Comparative Study
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