4-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoic acid | 916204-10-9

• 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)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoic acid
• 英文别名: (Z)-4-(4-((2-(4-chlorophenyl)cyclohept-1-enyl)methyl)piperazin-1-yl)benzoic acid；4-[4-[[2-(4-Chlorophenyl)-1-cycloheptenyl]methyl]-1-piperazinyl]benzoic Acid；4-[4-[[2-(4-chlorophenyl)cyclohepten-1-yl]methyl]piperazin-1-yl]benzoic acid
• CAS: 916204-10-9
• 化学式: C₂₅H₂₉ClN₂O₂
• 分子量: 424.97
• InChiKey: WJNIGAMHMUWMQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 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-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoic acid 在 盐酸 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 (R)-4-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)-N-((4-((1-(phenylthio)-4-(piperazin-1-yl)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide
  参考文献：
  名称：

  WO2024067818A1

  摘要：

  公开号：
• 作为产物：
  描述：

  ethyl 4-(4-((2-(4-chlorophenyl)cyclohept-1-ene-1-yl)methyl)piperazine-1-yl)benzoate 在 lithium hydroxide 、 水 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 生成 4-(4-((2-(4-chlorophenyl)cyclohept-1-en-1-yl)methyl)piperazin-1-yl)benzoic acid
  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

文献信息

• Apoptosis promoters
  申请人：Bruncko Milan

  公开号：US20070027135A1

  公开（公告）日：2007-02-01

  Compounds which inhibit the activity of anti-apoptotic family protein members, compositions containing the compounds and methods of treating diseases during which occur expression one or more than one of an anti-apoptotic family protein member are disclosed.

  本文披露了一种抑制抗凋亡家族蛋白成员活性的化合物、含有该化合物的组合物以及治疗在其中发生一个或多个抗凋亡家族蛋白成员表达的疾病的方法。
• Combination Therapy for Treating Cancer and Diagnostic Assays for Use Therein
  申请人：Shah Omar Jameel

  公开号：US20100227838A1

  公开（公告）日：2010-09-09

  The present disclosure relates to a combination of therapeutic agents for use in treating a patient a subject suffering from cancer. In addition, the present disclosure also relates to diagnostic assays useful in classification of patients for treatment with one or more therapeutic agents.

  本公开涉及一种治疗癌症患者的治疗剂组合。此外，本公开还涉及用于分类患者以接受一种或多种治疗剂治疗的诊断检测方法。
• APOPTOSIS PROMOTERS
  申请人：ABBOTT LABORATORIES

  公开号：EP1888543B1

  公开（公告）日：2012-08-01
• COMBINATION THERAPY FOR TREATING CANCER AND DIAGNOSTIC ASSAYS FOR USE THEREIN
  申请人：Abbott Laboratories

  公开号：EP2506853A1

  公开（公告）日：2012-10-10
• 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.