methyl (Z)-3-(3',5'-dimethoxyphenyl)-2-[(E)-1-(4-methylpiperazin-1-ylcarbamoyl)-2-phenylvinyl]-2-butenoate | 197979-66-1

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: methyl (Z)-3-(3',5'-dimethoxyphenyl)-2-[(E)-1-(4-methylpiperazin-1-ylcarbamoyl)-2-phenylvinyl]-2-butenoate
• 英文别名: (1Z,3E)-1-methyl-1-(3,5-dimethoxyphenyl)-2-methoxycarbonyl-3-[N-(4-methylpiperazin-1-yl)aminocarbonyl]-4-phenylbutadiene；methyl (Z)-3-(3,5-dimethoxyphenyl)-2-[(E)-3-[(4-methylpiperazin-1-yl)amino]-3-oxo-1-phenylprop-1-en-2-yl]but-2-enoate
• CAS: 197979-66-1
• 化学式: C₂₇H₃₃N₃O₅
• 分子量: 479.576
• InChiKey: CGYFOHOJSSVQRA-VUVXTBABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  35
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  80.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (Z)-3-(3',5'-dimethoxyphenyl)-2-[(E)-1-(4-methylpiperazin-1-ylcarbamoyl)-2-phenylvinyl]-2-butenoate 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 以420 g的产率得到methyl (Z)-3-(3',5'-dimethoxyphenyl)-2-[(E)-1-(4-methylpiperazin-1-ylcarbamoyl)-2-phenylvinyl]-2-butenoate hydrochloride
  参考文献：
  名称：

  1,4,4-二苯基丁二烯衍生物作为纤溶酶原激活物抑制剂1（PAI-1）生产的抑制剂的合成和评估

  摘要：

  合成了丁二烯酰亚胺1（T-686）衍生物，并评估了其对PAI-1产生的抑制活性及其ADMET（DMPK和毒理学）特性。在这些衍生物中，化合物15k（T-2639）在两个大鼠血栓形成模型中显示出良好的抗血栓形成活性，而不会影响出血时间，表明出血风险降低。我们还在本报告中描述了适用于使用Z，E选择性Stobbe缩合放大的15k实用合成方法。

  DOI：

  10.1016/j.bmc.2010.01.032
• 作为产物：
  描述：

  1-氨基-4-甲基哌嗪 、 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 methyl (Z)-3-(3',5'-dimethoxyphenyl)-2-[(E)-1-(4-methylpiperazin-1-ylcarbamoyl)-2-phenylvinyl]-2-butenoate
  参考文献：
  名称：

  Design, synthesis, and evaluation of orally active inhibitors of plasminogen activator inhibitor-1 (PAI-1) production

  摘要：

  A novel series of butadiene-imide 1 (T-686) derivatives having an inhibitory activity against PAI-1 production was synthesized and evaluated their biological activities and DMPK profiles, in which 15k (T-2639) was selected as the best compound based on its strong antithrombotic activity and good bioavailability. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.067

文献信息

• Butadiene derivatives and process for preparing thereof
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US06248743B1

  公开（公告）日：2001-06-19

  A novel butadiene derivative of the formula: wherein Ring A is heterocycle, or benzene being optionally substituted by lower alkyl, alkoxy, nitro, hydroxy, substituted or unsubstituted amino or halogen, Ring B is heterocycle, or benzene being optionally substituted by lower alkoxy, lower alkylenedioxy or di-lower alkylamino, R1 and R2 are each H or lower alkyl, one of —COR32 and —COR42 is carboxyl, and the other is carboxyl being optionally esterified, or the corresponding amide or pyrrolidine derivatives, or a pharmaceutically acceptable salt thereof. Said compounds show excellent PAI-1 inhibitory activity and are useful in the prophylaxis or treatment of various thromboses such as myocardial infarction, intra-atrial thrombus in atrial fibrillation, cerebral infarction, angina pectoris, stroke, pulmonary infarction, deep venous thrombus (DVT), disseminated intravascular coagulation syndrome (DIC), diabetic complications, restenosis after percutaneous transluminal coronary angioplasty (PTCA), etc.

  一种新颖的丁二烯衍生物，其结构式为：其中，环A为杂环或苯环，可选择性地被低级烷基、烷氧基、硝基、羟基、取代或未取代的氨基或卤素取代；环B为杂环或苯环，可选择性地被低级烷氧基、低级亚烷基二氧基或二低级烷基氨基取代；R1和R2各自为氢或低级烷基；其中—COR32和—COR42之一为羧基，另一为可选择性酯化的羧基，或相应的酰胺或吡咯烷衍生物，或其药学上可接受的盐。这些化合物表现出优异的PAI-1抑制活性，可用于预防或治疗各种血栓性疾病，如心肌梗死、心房颤动中的心房内血栓、脑梗死、心绞痛、中风、肺栓塞、深静脉血栓（DVT）、弥散性血管内凝血综合征（DIC）、糖尿病并发症、经皮冠状动脉腔内成形术（PTCA）后的再狭窄等。
• BUTADIENE DERIVATIVES AND PROCESS FOR PREPARING THEREOF
  申请人：TANABE SEIYAKU CO., LTD.

  公开号：EP0889879B1

  公开（公告）日：2002-06-12
• US6248743B1
  申请人：——

  公开号：US6248743B1

  公开（公告）日：2001-06-19
• Synthesis and evaluation of 1,4-diphenylbutadiene derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1) production
  作者：Hiroshi Miyazaki、Hiroshi Sai、Hiroshi Ohmizu、Jun Murakami、Akio Ohtani、Tsuyoshi Ogiku

  DOI：10.1016/j.bmc.2010.01.032

  日期：2010.3

  antithrombotic activity in two rat thrombosis models without affecting bleeding time, indicating reduction of haemorrhagic risk. We also describe in this report a practical synthesis of 15k suitable for scale-up using Z,E-selective Stobbe condensation.

  合成了丁二烯酰亚胺1（T-686）衍生物，并评估了其对PAI-1产生的抑制活性及其ADMET（DMPK和毒理学）特性。在这些衍生物中，化合物15k（T-2639）在两个大鼠血栓形成模型中显示出良好的抗血栓形成活性，而不会影响出血时间，表明出血风险降低。我们还在本报告中描述了适用于使用Z，E选择性Stobbe缩合放大的15k实用合成方法。
• Design, synthesis, and evaluation of orally active inhibitors of plasminogen activator inhibitor-1 (PAI-1) production
  作者：Hiroshi Miyazaki、Tsuyoshi Ogiku、Hiroshi Sai、Hiroshi Ohmizu、Jun Murakami、Akio Ohtani

  DOI：10.1016/j.bmcl.2008.10.067

  日期：2008.12

  A novel series of butadiene-imide 1 (T-686) derivatives having an inhibitory activity against PAI-1 production was synthesized and evaluated their biological activities and DMPK profiles, in which 15k (T-2639) was selected as the best compound based on its strong antithrombotic activity and good bioavailability. (C) 2008 Elsevier Ltd. All rights reserved.