Ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(5-cyano-2-benzothiazolyl)-2-ethoxycarbonylpropionate | 150611-03-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: Ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(5-cyano-2-benzothiazolyl)-2-ethoxycarbonylpropionate
• 英文别名: diethyl 2-[(5-cyano-1,3-benzothiazol-2-yl)methyl]-2-[4-[(3S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-3-yl]oxyphenyl]propanedioate
• CAS: 150611-03-3
• 化学式: C₃₁H₃₅N₃O₇S
• 分子量: 593.701
• InChiKey: LRKQRVDQUNJIDK-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  156
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(5-cyano-2-benzothiazolyl)-2-ethoxycarbonylpropionate 在 盐酸 、 乙醇 、 氨 作用下， 以 乙醇 为溶剂， 反应 49.5h， 以17%的产率得到3-(5-amidino-1,3-benzothiazol-2-yl)-2-{4-[(3S)-pyrrolidin-3-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：

  diethyl 2-(4-hydroxyphenyl)malonate 在 sodium hydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 120.0h， 生成 Ethyl 2-[4-[((3S)-1-tert-butoxycarbonyl-3-pyrrolidinyl)oxy]phenyl]-3-(5-cyano-2-benzothiazolyl)-2-ethoxycarbonylpropionate
  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

• Aromatic amidine derivatives and salts thereof
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP0540051B1

  公开（公告）日：1996-04-03
• US5576343A
  申请人：——

  公开号：US5576343A

  公开（公告）日：1996-11-19
• US5620991A
  申请人：——

  公开号：US5620991A

  公开（公告）日：1997-04-15
• US5866577A
  申请人：——

  公开号：US5866577A

  公开（公告）日：1999-02-02
• US5962695A
  申请人：——

  公开号：US5962695A

  公开（公告）日：1999-10-05