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Title
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A novel factor Xa inhibitor: structure-activity relationships and selectivity between factor Xa and thrombin.
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Authors
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S.Katakura,
T.Nagahara,
T.Hara,
M.Iwamoto.
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Ref.
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Biochem Biophys Res Commun, 1993,
197,
965-972.
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PubMed id
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Abstract
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A series of 3-amidinoaryl-2-[4-[ [(3S)-3-pyrrolidinyl]oxy]phenyl] propanoic
acids have been investigated for development of a novel factor Xa inhibitor,
possessing a potent inhibitory activity for factor Xa and a selectivity for
factor Xa compared to thrombin. In order to study the structure-activity
relationships and the selectivity, models of factors Xa complexes formed with
the inhibitors were constructed on the basis of X-ray crystallographic data of a
trypsin-inhibitor complex. The models showed that the binding mode of the
inhibitors to the S1 pocket of the enzyme accounted for the structure-activity
relationships and that the difference between Gln192 of factor Xa and Glu192 of
thrombin had a key role in the selectivity.
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