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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
1993-6-9
|
| pubmed:abstractText |
A novel series of nonpeptide angiotensin II (AII) receptor antagonists is reported, derived from linkage of the biphenylyltetrazole moiety found in previously described antagonists via a methyleneoxy chain to the 4-position of a 3-substituted 2,6-dialkylpyridine. When evaluated in an in vitro binding assay using a guinea pig adrenal membrane preparation, compounds in this series generally gave IC50 values in the range 0.005-0.5 microM. A variety of substituents was found to be effective at the 3-position of the pyridine ring. On intravenous administration in a normotensive rat model, the more potent compounds inhibited the AII-induced pressor response with ED50 values in the range 0.1-1.0 mg/kg. One of the compounds, 2-ethyl-5,6,7,8-tetrahydro-4-([2'-(1H-tetrazol-5-yl)biphenyl-4y l] methoxy)quinoline (26), demonstrated good oral activity in two rat models. At doses in the range 1-10 mg/kg po in AII-infused, conscious, normotensive rats, the compound exhibited a dose-related inhibition of the pressor response with a good duration of action at the higher doses. In a renal hypertensive rat model compound 26 showed a rapid and sustained lowering of blood pressure at a dose of 5 mg/kg po. Based on its profile, this compound, designated ICI D6888, has been selected for evaluation in volunteers.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin Receptor Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Antihypertensive Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Biphenyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
30
|
| pubmed:volume |
36
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
N
|
| pubmed:pagination |
1245-54
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:8487261-Adrenal Glands,
pubmed-meshheading:8487261-Angiotensin II,
pubmed-meshheading:8487261-Angiotensin Receptor Antagonists,
pubmed-meshheading:8487261-Animals,
pubmed-meshheading:8487261-Antihypertensive Agents,
pubmed-meshheading:8487261-Biphenyl Compounds,
pubmed-meshheading:8487261-Blood Pressure,
pubmed-meshheading:8487261-Cell Membrane,
pubmed-meshheading:8487261-Female,
pubmed-meshheading:8487261-Guinea Pigs,
pubmed-meshheading:8487261-Hypertension, Renal,
pubmed-meshheading:8487261-Male,
pubmed-meshheading:8487261-Models, Molecular,
pubmed-meshheading:8487261-Molecular Conformation,
pubmed-meshheading:8487261-Molecular Structure,
pubmed-meshheading:8487261-Quinolines,
pubmed-meshheading:8487261-Rats,
pubmed-meshheading:8487261-Structure-Activity Relationship
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
New nonpeptide angiotensin II receptor antagonists. 3. Synthesis, biological properties, and structure-activity relationships of 2-alkyl-4-(biphenylylmethoxy)pyridine derivatives.
|
| pubmed:affiliation |
Department of Chemistry, ZENECA Pharmaceuticals, Macclesfield, Cheshire, U.K.
|
| pubmed:publicationType |
Journal Article
|