ethyl 3-(6-amidino-1-ethyl-1H-indol-2-yl)-2-[4-(piperidin-4-yloxy)phenyl]propanoate | 701305-54-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 3-(6-amidino-1-ethyl-1H-indol-2-yl)-2-[4-(piperidin-4-yloxy)phenyl]propanoate
• 英文别名: Ethyl 3-(6-carbamimidoyl-1-ethylindol-2-yl)-2-(4-piperidin-4-yloxyphenyl)propanoate
• CAS: 701305-54-6
• 化学式: C₂₇H₃₄N₄O₃
• 分子量: 462.592
• InChiKey: MAERXHSWGIIHAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  102
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  乙基乙酰亚胺盐酸盐 、 ethyl 3-(6-amidino-1-ethyl-1H-indol-2-yl)-2-[4-(piperidin-4-yloxy)phenyl]propanoate 在 三乙胺 、 盐酸 作用下， 以 乙醇 为溶剂， 反应 18.5h， 以0.56 g的产率得到3-(6-amidino-1-ethyl-1H-indol-2-yl)-2-[4-(1-ethanimidoylpiperidin-4-yloxy)phenyl]propanoic acid dihydrochloride
  参考文献：
  名称：

  Design, synthesis and biological activity of amidinobicyclic compounds (derivatives of DX-9065a) as factor Xa inhibitors: SAR study of S1 and aryl binding sites

  摘要：

  Since factor Xa (fXa) plays a pivotal role in the blood coagulation cascade, inhibition of fXa is thought to be an effective treatment for a variety of thrombotic events. (2,)-2-[4-[[(3S)-l-Acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphthyl)propanoic acid hydrochloride pentahydrate (DX-9065a) was previously found in our laboratory as a novel orally active factor Xa inhibitor. DX-9065a exhibits a strong inhibitory activity toward fXa by occupying the substrate recognition (called SI) sites and aryl binding sites of fXa. Herein we describe conversions of the amidinonaphthalene and the acetimidoylpyrrolidine moieties of DX-9065a. Some compounds showed remarkably increased in vitro anti-factor Xa and PRCT activities compared with those of DX9065a. The most promising compound 38 showed four times the prolongation of APTT against DX-9065a after oral administration to rats. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.032
• 作为产物：
  描述：

  2-(4-羟苯基)-2-氧代乙酸乙酯 在 palladium(II) oxide 、 barium sulfate 盐酸 、 乙醇 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 84.5h， 生成 ethyl 3-(6-amidino-1-ethyl-1H-indol-2-yl)-2-[4-(piperidin-4-yloxy)phenyl]propanoate
  参考文献：
  名称：

  Design, synthesis and biological activity of amidinobicyclic compounds (derivatives of DX-9065a) as factor Xa inhibitors: SAR study of S1 and aryl binding sites

  摘要：

  Since factor Xa (fXa) plays a pivotal role in the blood coagulation cascade, inhibition of fXa is thought to be an effective treatment for a variety of thrombotic events. (2,)-2-[4-[[(3S)-l-Acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphthyl)propanoic acid hydrochloride pentahydrate (DX-9065a) was previously found in our laboratory as a novel orally active factor Xa inhibitor. DX-9065a exhibits a strong inhibitory activity toward fXa by occupying the substrate recognition (called SI) sites and aryl binding sites of fXa. Herein we describe conversions of the amidinonaphthalene and the acetimidoylpyrrolidine moieties of DX-9065a. Some compounds showed remarkably increased in vitro anti-factor Xa and PRCT activities compared with those of DX9065a. The most promising compound 38 showed four times the prolongation of APTT against DX-9065a after oral administration to rats. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.032

文献信息

• Design, synthesis and biological activity of amidinobicyclic compounds (derivatives of DX-9065a) as factor Xa inhibitors: SAR study of S1 and aryl binding sites
  作者：Satoshi Komoriya、Naoaki Kanaya、Takayasu Nagahara、Asako Yokoyama、Kazue Inamura、Yukio Yokoyama、Shin-ichi Katakura、Tsuyoshi Hara

  DOI：10.1016/j.bmc.2004.02.032

  日期：2004.5

  Since factor Xa (fXa) plays a pivotal role in the blood coagulation cascade, inhibition of fXa is thought to be an effective treatment for a variety of thrombotic events. (2,)-2-[4-[[(3S)-l-Acetimidoyl-3-pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphthyl)propanoic acid hydrochloride pentahydrate (DX-9065a) was previously found in our laboratory as a novel orally active factor Xa inhibitor. DX-9065a exhibits a strong inhibitory activity toward fXa by occupying the substrate recognition (called SI) sites and aryl binding sites of fXa. Herein we describe conversions of the amidinonaphthalene and the acetimidoylpyrrolidine moieties of DX-9065a. Some compounds showed remarkably increased in vitro anti-factor Xa and PRCT activities compared with those of DX9065a. The most promising compound 38 showed four times the prolongation of APTT against DX-9065a after oral administration to rats. (C) 2004 Elsevier Ltd. All rights reserved.