4-(4-((2-(4-chlorophenyl)cyclohex-1-enyl)methyl)piperazin-1-yl)benzoic acid | 916204-04-1

• 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: 4-(4-((2-(4-chlorophenyl)cyclohex-1-enyl)methyl)piperazin-1-yl)benzoic acid
• 英文别名: 4-[4-[[2-(4-chlorophenyl)cyclohexen-1-yl]methyl]piperazin-1-yl]benzoic acid
• CAS: 916204-04-1
• 化学式: C₂₄H₂₇ClN₂O₂
• 分子量: 410.944
• InChiKey: JDBAUAGBPSVDSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[[(1R)-3-(4-吗啉)-1-[(苯基硫代)甲基]丙基]氨基]-3-[(三氟甲基)磺酰基]苯磺酰胺 、 4-(4-((2-(4-chlorophenyl)cyclohex-1-enyl)methyl)piperazin-1-yl)benzoic acid 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 15.0h， 生成 N-(4-(4-((2-(4-chlorophenyl)cyclohex-1-en-1-yl)methyl)piperazin-1-yl)benzoyl)-4-(((1R)-3-(morpholin-4-yl)-1-((phenylsulfanyl)methyl)propyl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide
  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：

  ethyl 4-(4-((2-(4-chlorophenyl)cyclohex-1-enyl)methyl)piperazin-1-yl)benzoate 在 lithium hydroxide monohydrate 、 水 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 4-(4-((2-(4-chlorophenyl)cyclohex-1-enyl)methyl)piperazin-1-yl)benzoic acid
  参考文献：
  名称：

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

  摘要：

  公开了抑制抗凋亡Bcl-2蛋白活性的化合物，包含这些化合物的组合物以及治疗表达抗凋亡Bcl-2蛋白疾病的方法。

  公开号：

  US20100184766A1

文献信息

• APOPTOSIS-INDUCING AGENTS FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
  申请人：Kunzer Aaron R.

  公开号：US20100184766A1

  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.

  公开了抑制抗凋亡Bcl-2蛋白活性的化合物，包含这些化合物的组合物以及治疗表达抗凋亡Bcl-2蛋白疾病的方法。
• Apoptosis-inducing agents for the treatment of cancer and immune and autoimmune diseases
  申请人：Abbott Laboratories

  公开号：US08338466B2

  公开（公告）日：2012-12-25

  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.

  本发明涉及一些化合物，其抑制抗凋亡Bcl-2蛋白的活性，包含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 AGENT FOR THE TREATMENT OF CANCER AND IMMUNE AND AUTOIMMUNE DISEASES
  申请人：AbbVie Inc.

  公开号：US20160002187A1

  公开（公告）日：2016-01-07

  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.

  公开了一种抑制抗凋亡Bcl-2蛋白活性的化合物，包含这些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。
• APOPTOSIS PROMOTERS
  申请人：ABBOTT LABORATORIES

  公开号：EP1888543B1

  公开（公告）日：2012-08-01
• Apoptosis Promoters
  申请人：Elmore Steven W.

  公开号：US20080194691A1

  公开（公告）日：2008-08-14

  Compounds of formula (I), in which B 1 and X 1 are together alkylene which is unsubstituted or substituted with ═O and having one CH2 moiety unreplaced or replaced with CH═CH, O, NH or N(alkyl), which inhibit the activity of antiapoptotic Bcl-2 family protein members, compositions containing the compounds and methods of treating diseases during which are expressed one or more than one of an anti-apoptotic family protein member are disclosed.