Rational Design, Synthesis, and Structure-Activity Relationships of Novel Factor Xa Inhibitors:(2-Substituted-4-amidinophenyl) pyruvic and-propionic Acids 1

…, M Takahashi, M Takayanagi, K Takenaka…

文献索引：Sagi, Kazuyuki; Nakagawa, Tadakiyo; Yamanashi, Masahiro; Makino, Shingo; Takahashi, Mitsuo; Takayanagi, Masaru; Takenaka, Kaoru; Suzuki, Nobuyasu; Oono, Seiji; Kataoka, Noriyasu; Ishikawa, Kohki; Shima, Sayaka; Fukuda, Yumiko; Kayahara, Takashi; Takehana, Shunji; Shima, Yoichiro; Tashiro, Kazumi; Yamamoto, Hiroshi; Yoshimoto, Ryota; Iwata, Seinosuke; Tsuji, Takashi; Sakurai, Kuniya; Shoji, Masataka Journal of Medicinal Chemistry, 2003 , vol. 46, # 10 p. 1845 - 1857

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被引用次数: 15

摘要

An inhibitor of factor Xa (fXa), the m-substituted benzamidine AXC1578 (1a), was structurally modified with the aim of increasing its potency. In particular, pyruvic acid and propionic acid substituents were incorporated into the P1 benzamidine moiety to introduce a favorable interaction with the oxy-anion hole in the catalytic triad region of fXa. This strategy was based on computational docking studies using the extracted active site of fXa. The validity ...