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Title
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Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites.
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Authors
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S.Komoriya,
N.Haginoya,
S.Kobayashi,
T.Nagata,
A.Mochizuki,
M.Suzuki,
T.Yoshino,
H.Horino,
T.Nagahara,
M.Suzuki,
Y.Isobe,
T.Furugoori.
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Ref.
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Bioorg Med Chem Lett, 2005,
13,
3927-3954.
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PubMed id
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Abstract
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Compound 7 was identified as the active metabolite of 6 by HPLC and mass
spectral analysis. Modification of lead compound 7 by transformation of its
N-oxide 6-6 biaryl ring system and fused aromatics produced a series of
non-basic fXa inhibitors with excellent potency in anti-fXa and anticoagulant
assays. The optimized compounds 73b and 75b showed sub to one digit micromolar
anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in
plasma of rats orally administered with 1mg/kg of compound 75b.
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