Title of article :
Design, synthesis, and biological activity of non-basic compounds as factor Xa inhibitors: SAR study of S1 and aryl binding sites Original Research Article
Author/Authors :
Satoshi Komoriya، نويسنده , , Noriyasu Haginoya، نويسنده , , Shozo Kobayashi، نويسنده , , Tsutomu Nagata، نويسنده , , Akiyoshi Mochizuki، نويسنده , , Masanori Suzuki، نويسنده , , Toshiharu Yoshino، نويسنده , , Haruhiko Horino، نويسنده , , Takayasu Nagahara، نويسنده , , Makoto Suzuki، نويسنده , , Yumiko Isobe، نويسنده , , Taketoshi Furugoori، نويسنده ,
Abstract :
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 1 mg/kg of compound 75b.
Keywords :
Factor Xa , Anticoagulant , None basic compound , Orally active compound
