Linked Life Data

1635059

Source:http://linkedlifedata.com/resource/pubmed/id/1635059

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1992-8-26
pubmed:abstractText
We have shown that the pyrrolidinylmethyl substituent on the lactam nitrogen (N1) of benzazepinone and benzothiazepinone calcium channel blocking agents is resistant to metabolic deamination and generally increases the duration and potency of antihypertensive activity in spontaneously hypertensive rats (SHR) relative to (N,N-dimethylamino)ethyl analogs. Additionally, compounds possessing a substituent on the fused aromatic ring are more resistant to metabolic deacylation of the C3 hydroxy function, which may explain why aromatic substituents also frequently increase the potency and/or duration of antihypertensive activity. Our data also indicate the increased antihypertensive activity associated with these structural modifications is independent of any effects of potency in vitro. Overall, we interpret these results to indicate that these structural modifications improve antihypertensive activity as a result of increased metabolic stability and, consequently, oral bioavailability.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2623
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
35
pubmed:owner
NLM
pubmed:authorsComplete
N
pubmed:pagination
2610-7
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Benzazepinone calcium channel blockers. 5. Effects on antihypertensive activity associated with N1 and aromatic substituents.
pubmed:affiliation
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
pubmed:publicationType
Journal Article, In Vitro