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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2005-5-31
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pubmed:abstractText |
We describe the structure-based design, synthesis, and enzymatic activity of a series of substituted pyrazinones as inhibitors of the TF/VIIa complex. These inhibitors contain substituents meta to the P(1) amidine designed to explore additional interactions with the VIIa residues in the so-called 'S(1) side pocket'. A crystal structure of the designed inhibitors demonstrates the ability of the P(1) side pocket moiety to engage Lys192 and main chain of Gly216 via hydrogen bond interactions, thus, providing additional possibility for chemical modification to improve selectivity and/or physical properties of inhibitors.
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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 |
Jun
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pubmed:issn |
0960-894X
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pubmed:author |
pubmed-author:KurumbailRavi GRG,
pubmed-author:KusturinCarrie LCL,
pubmed-author:NeumannWilliam LWL,
pubmed-author:PodaGennadiy IGI,
pubmed-author:RahmanHayat KHK,
pubmed-author:SampleKirby RKR,
pubmed-author:SchweitzerBarbara ABA,
pubmed-author:SouthMichael SMS,
pubmed-author:StallingsWilliam CWC,
pubmed-author:StegemanRoderick ARA,
pubmed-author:StevensAnna MAM
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3006-11
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15913999-Benzamidines,
pubmed-meshheading:15913999-Binding Sites,
pubmed-meshheading:15913999-Drug Design,
pubmed-meshheading:15913999-Factor VIIa,
pubmed-meshheading:15913999-Fibrinolytic Agents,
pubmed-meshheading:15913999-Inhibitory Concentration 50,
pubmed-meshheading:15913999-Models, Molecular,
pubmed-meshheading:15913999-Protein Binding,
pubmed-meshheading:15913999-Pyrazines,
pubmed-meshheading:15913999-Serine Proteinase Inhibitors,
pubmed-meshheading:15913999-Structure-Activity Relationship
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pubmed:year |
2005
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pubmed:articleTitle |
Structure-based design and synthesis of pyrazinones containing novel P1 'side pocket' moieties as inhibitors of TF/VIIa.
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pubmed:affiliation |
Department of Medicinal and Combinatorial Chemistry, Pfizer Corp., 800 N. Lindbergh Blvd., St. Louis, MO 63167, USA. barbara.a.schweitzer@pfizer.com
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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