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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2000-9-8
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pubmed:abstractText |
The synthesis and structure-activity relationship (SAR) studies of a series of 4'-oxazolyl-N-(3,4-dimethyl-5-isoxazolyl)[1, 1'-biphenyl]-2-sulfonamide derivatives as endothelin-A (ET(A)) receptor antagonists are described. The data reveal a remarkable improvement in potency and metabolic stability when the 4'-position of the biphenylsulfonamide is substituted with an oxazole ring. Additional 2'-substitution of an acylaminomethyl group further increased the binding activity and provided one of the first subnanomolar ET(A)-selective antagonists in the biphenylsulfonamide series (17, ET(A) K(i) = 0.2 nM). Among the compounds described, 3 (N-(3,4-dimethyl-5-isoxazolyl)-4'-(2-oxazolyl)[1, 1'-biphenyl]-2-sulfonamide; BMS-193884) had the optimum pharmacological profile and was therefore selected as a clinical candidate for studies in congestive heart failure.
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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 |
Aug
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BarrishJ CJC,
pubmed-author:BirdEE,
pubmed-author:HOSS,
pubmed-author:LeithLL,
pubmed-author:LiuE CEC,
pubmed-author:MarinoAA,
pubmed-author:MathurAA,
pubmed-author:MorelandSS,
pubmed-author:MorrisonR ARA,
pubmed-author:MurugesanNN,
pubmed-author:SpergelSS,
pubmed-author:SteinP DPD,
pubmed-author:WaldropJJ,
pubmed-author:WebbM LML,
pubmed-author:ZhangRR
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pubmed:issnType |
Print
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pubmed:day |
10
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pubmed:volume |
43
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3111-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:10956219-Administration, Oral,
pubmed-meshheading:10956219-Animals,
pubmed-meshheading:10956219-Biological Availability,
pubmed-meshheading:10956219-Blood Pressure,
pubmed-meshheading:10956219-Carotid Arteries,
pubmed-meshheading:10956219-Drug Evaluation, Preclinical,
pubmed-meshheading:10956219-Hypertension,
pubmed-meshheading:10956219-Injections, Intravenous,
pubmed-meshheading:10956219-Macaca fascicularis,
pubmed-meshheading:10956219-Muscle, Smooth, Vascular,
pubmed-meshheading:10956219-Muscle Contraction,
pubmed-meshheading:10956219-Oxazoles,
pubmed-meshheading:10956219-Rabbits,
pubmed-meshheading:10956219-Radioligand Assay,
pubmed-meshheading:10956219-Rats,
pubmed-meshheading:10956219-Receptor, Endothelin A,
pubmed-meshheading:10956219-Receptors, Endothelin,
pubmed-meshheading:10956219-Structure-Activity Relationship,
pubmed-meshheading:10956219-Sulfonamides
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pubmed:year |
2000
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pubmed:articleTitle |
Biphenylsulfonamide endothelin receptor antagonists. 2. Discovery of 4'-oxazolyl biphenylsulfonamides as a new class of potent, highly selective ET(A) antagonists.
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pubmed:affiliation |
Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-5400, USA. murugesan@bms.com
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pubmed:publicationType |
Journal Article,
In Vitro
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