(4R)-4-[(2-aminobenzimidazole-5-carbonyl)amino]-5-[5-amidino-2-(2-carboxy-2-oxoethyl)phenoxy]pentanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4R)-4-[(2-aminobenzimidazole-5-carbonyl)amino]-5-[5-amidino-2-(2-carboxy-2-oxoethyl)phenoxy]pentanoic acid
• 英文别名: (4R)-4-[(2-amino-3H-benzimidazole-5-carbonyl)amino]-5-[5-carbamimidoyl-2-(2-carboxy-2-oxoethyl)phenoxy]pentanoic acid
• 化学式: C₂₃H₂₄N₆O₇
• 分子量: 496.48
• InChiKey: ZBDNMPDGDZEMPE-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  235
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3,4-二氨基苯甲酸甲酯 在 盐酸 、 乙醇 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 50.33h， 生成 (4R)-4-[(2-aminobenzimidazole-5-carbonyl)amino]-5-[5-amidino-2-(2-carboxy-2-oxoethyl)phenoxy]pentanoic acid
  参考文献：
  名称：

  Optimization of a coagulation factor VIIa inhibitor found in factor Xa inhibitor library☆

  摘要：

  An inhibitor of the complex of factor Vila and tissue factor (fVIIa/TF), 2-substituted-4-amidinophenylpyruvic acid la, was structurally modified with the aim of increasing its potency and selectivity. The lead compound la was originally found in our factor Xa (fXa) inhibitor library on the basis of structural similarity of the primary binding sites of tVIIa and fXa. The design was based on computational docking studies using the extracted active site of tVIIa. Compound 1j was found to inhibit factor VIIa/TF at nanomolar concentration with improved selectivity versus fXa and thrombin and it preferentially prolonged the clotting time in the TF-dependent extrinsic pathway. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.12.033

文献信息

• Optimization of a coagulation factor VIIa inhibitor found in factor Xa inhibitor library☆
  作者：Kazuyuki Sagi、Koichi Fujita、Masayuki Sugiki、Mitsuo Takahashi、Shunji Takehana、Kazumi Tashiro、Takashi Kayahara、Masahiro Yamanashi、Yumiko Fukuda、Seiji Oono

  DOI：10.1016/j.bmc.2004.12.033

  日期：2005.3.1

  An inhibitor of the complex of factor Vila and tissue factor (fVIIa/TF), 2-substituted-4-amidinophenylpyruvic acid la, was structurally modified with the aim of increasing its potency and selectivity. The lead compound la was originally found in our factor Xa (fXa) inhibitor library on the basis of structural similarity of the primary binding sites of tVIIa and fXa. The design was based on computational docking studies using the extracted active site of tVIIa. Compound 1j was found to inhibit factor VIIa/TF at nanomolar concentration with improved selectivity versus fXa and thrombin and it preferentially prolonged the clotting time in the TF-dependent extrinsic pathway. (C) 2005 Elsevier Ltd. All rights reserved.