Title of article :
Design, synthesis, and biological activity of novel factor Xa inhibitors: Improving metabolic stability by S1 and S4 ligand modification Original Research Article
Author/Authors :
Satoshi Komoriya، نويسنده , , Shozo Kobayashi، نويسنده , , Ken Osanai، نويسنده , , Toshiharu Yoshino، نويسنده , , Tsutomu Nagata، نويسنده , , Noriyasu Haginoya، نويسنده , , Yumi Nakamoto، نويسنده , , Akiyoshi Mochizuki، نويسنده , , Takayasu Nagahara، نويسنده , , Makoto Suzuki، نويسنده , , Takashi Shimada، نويسنده , , Kengo Watanabe، نويسنده , , Yumiko Isobe، نويسنده , , Taketoshi Furugoori، نويسنده ,
Abstract :
Serine protease factor xa (fXa) inhibitor 1 showed good ex vivo anti-fXa activity upon oral administration in rats. However, it has been revealed that 1 had low metabolic stability against human liver microsomes. To improve the metabolic stability, we attempted to modify the S1 and S4 ligands of 1. These modifications resulted in compound 34b, which exhibited selective anti-fXa activity and excellent anti-coagulation activity.
Keywords :
Anti-coagulant , Orally active compound , Non-basic compound , Metabolic stability , Factor Xa
