ethyl 4-(4-((2-bromocyclohex-1-enyl)methyl)piperazin-1-yl)benzoate | 1065604-49-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: ethyl 4-(4-((2-bromocyclohex-1-enyl)methyl)piperazin-1-yl)benzoate
• 英文别名: ethyl 4-[4-[(2-bromocyclohexen-1-yl)methyl]piperazin-1-yl]benzoate
• CAS: 1065604-49-0
• 化学式: C₂₀H₂₇BrN₂O₂
• 分子量: 407.351
• InChiKey: OPGSCAJQSFEFGQ-UHFFFAOYSA-N

物化性质

• 沸点：
  510.4±50.0 °C(Predicted)
• 密度：
  1.310±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-((2-bromocyclohex-1-enyl)methyl)piperazin-1-yl)benzoate 、 4-氯苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 3.0h， 以89%的产率得到ethyl 4-(4-((2-(4-chlorophenyl)cyclohex-1-enyl)methyl)piperazin-1-yl)benzoate
  参考文献：
  名称：

  Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins

  摘要：

  Overexpression of prosurvival proteins such as Bcl-2 and Bcl-X-L has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-X-L, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally bioavailable. Herein, we report that targeted modifications at three key positions of 1 resulted in a 20-fold improvement in the pharmacokinetic/pharmacodynamic relationship (PK/PD) between oral exposure (AUC) and in vitro efficacy in human tumor cell lines (EC50). The resulting compound, 2 (ABT-263), is orally efficacious in an established xenograft model of human small cell lung cancer, inducing complete tumor regressions in all animals. Compound 2 is currently in multiple phase 1 clinical trials in patients with small cell lung cancer and hematological malignancies.

  DOI：

  10.1021/jm800669s
• 作为产物：
  描述：

  2-溴-1-环己烯-1-甲醛 、 4-(1-哌嗪基)苯甲酸乙酯 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 ethyl 4-(4-((2-bromocyclohex-1-enyl)methyl)piperazin-1-yl)benzoate
  参考文献：
  名称：

  APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES

  摘要：

  揭示了一种抑制抗凋亡Bcl-2蛋白活性的化合物，含有这些化合物的组合物以及治疗在其中表达抗凋亡Bcl-2蛋白的疾病的方法。

  公开号：

  US20100184750A1

文献信息

• APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
  申请人：Hexamer Laura A.

  公开号：US20100184750A1

  公开（公告）日：2010-07-22

  Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.

  揭示了一种抑制抗凋亡Bcl-2蛋白活性的化合物，含有这些化合物的组合物以及治疗在其中表达抗凋亡Bcl-2蛋白的疾病的方法。
• Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
  申请人：Hexamer Laura A.

  公开号：US08426422B2

  公开（公告）日：2013-04-23

  Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.

  本发明揭示了一种抑制抗凋亡Bcl-2蛋白活性的化合物，包含该化合物的组合物以及用于治疗表达抗凋亡Bcl-2蛋白的疾病的方法。
• US8426422B2
  申请人：——

  公开号：US8426422B2

  公开（公告）日：2013-04-23
• [EN] APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES<br/>[FR] AGENTS INDUISANT L'APOPTOSE DESTINÉS AU TRAITEMENT DU CANCER ET DE MALADIES IMMUNES ET AUTO-IMMUNES
  申请人：ABBOTT LAB

  公开号：WO2010083441A2

  公开（公告）日：2010-07-22

  Disclosed are compounds of formula (I) which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.
• Discovery of an Orally Bioavailable Small Molecule Inhibitor of Prosurvival B-Cell Lymphoma 2 Proteins
  作者：Cheol-Min Park、Milan Bruncko、Jessica Adickes、Joy Bauch、Hong Ding、Aaron Kunzer、Kennan C. Marsh、Paul Nimmer、Alexander R. Shoemaker、Xiaohong Song、Stephen K. Tahir、Christin Tse、Xilu Wang、Michael D. Wendt、Xiufen Yang、Haichao Zhang、Stephen W. Fesik、Saul H. Rosenberg、Steven W. Elmore

  DOI：10.1021/jm800669s

  日期：2008.11.13

  Overexpression of prosurvival proteins such as Bcl-2 and Bcl-X-L has been correlated with tumorigenesis and resistance to chemotherapy, and thus, the development of antagonists of these proteins may provide a novel means for the treatment of cancer. We recently described the discovery of 1 (ABT-737), which binds Bcl-2, Bcl-X-L, and Bcl-w with high affinity, shows robust antitumor activity in murine tumor xenograft models, but is not orally bioavailable. Herein, we report that targeted modifications at three key positions of 1 resulted in a 20-fold improvement in the pharmacokinetic/pharmacodynamic relationship (PK/PD) between oral exposure (AUC) and in vitro efficacy in human tumor cell lines (EC50). The resulting compound, 2 (ABT-263), is orally efficacious in an established xenograft model of human small cell lung cancer, inducing complete tumor regressions in all animals. Compound 2 is currently in multiple phase 1 clinical trials in patients with small cell lung cancer and hematological malignancies.