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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
1999-1-27
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pubmed:abstractText |
Replacement of the amidinopiperidine P1 group of 3-benzylsulfonylamino-6-methyl-2-pyridinone acetamide thrombin inhibitor L-373,890 (2) with a mildly basic 5-linked 2-amino-6-methylpyridine results in an equipotent compound L-374,087 (5, Ki = 0.5 nM). Compound 5 is highly selective for thrombin over trypsin, is efficacious in the rat ferric chloride model of arterial thrombosis and is orally bioavailable in dogs and cynomolgus monkeys. The structural basis for the critical importance of both methyl groups in 5 was confirmed by X-ray crystallography.
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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 |
Apr
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:ChefRR,
pubmed-author:ChenI WIW,
pubmed-author:CoonJ MJM,
pubmed-author:CutronaK JKJ,
pubmed-author:DorseyB DBD,
pubmed-author:DyerD LDL,
pubmed-author:GardellS JSJ,
pubmed-author:KruegerJ AJA,
pubmed-author:LewisS DSD,
pubmed-author:LinJ HJH,
pubmed-author:LucasB JBJJr,
pubmed-author:LyleE AEA,
pubmed-author:LyonsK RKR,
pubmed-author:McDonoughC MCM,
pubmed-author:Naylor-OlsenA MAM,
pubmed-author:SandersonP EPE,
pubmed-author:ShaferJ AJA,
pubmed-author:StranieriM TMT,
pubmed-author:VaccaJ PJP,
pubmed-author:VastagKK
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
817-22
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:9871547-Administration, Oral,
pubmed-meshheading:9871547-Animals,
pubmed-meshheading:9871547-Anticoagulants,
pubmed-meshheading:9871547-Biological Availability,
pubmed-meshheading:9871547-Chlorides,
pubmed-meshheading:9871547-Crystallography, X-Ray,
pubmed-meshheading:9871547-Dogs,
pubmed-meshheading:9871547-Ferric Compounds,
pubmed-meshheading:9871547-Kinetics,
pubmed-meshheading:9871547-Macaca fascicularis,
pubmed-meshheading:9871547-Models, Molecular,
pubmed-meshheading:9871547-Molecular Structure,
pubmed-meshheading:9871547-Pyridones,
pubmed-meshheading:9871547-Rats,
pubmed-meshheading:9871547-Structure-Activity Relationship,
pubmed-meshheading:9871547-Sulfonamides,
pubmed-meshheading:9871547-Thrombin,
pubmed-meshheading:9871547-Thrombosis,
pubmed-meshheading:9871547-Trypsin
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pubmed:year |
1998
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pubmed:articleTitle |
L-374,087, an efficacious, orally bioavailable, pyridinone acetamide thrombin inhibitor.
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pubmed:affiliation |
Department of Biological Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
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pubmed:publicationType |
Journal Article
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