(R)-5-(4-chlorophenyl)-4-(3-(4-(4-(4-(4-(dimethylamino)-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-1-isopropyl-2-methyl-1H-pyrrole-3-carboxylic acid | 1384513-01-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (R)-5-(4-chlorophenyl)-4-(3-(4-(4-(4-(4-(dimethylamino)-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-1-isopropyl-2-methyl-1H-pyrrole-3-carboxylic acid
• 英文别名: 5-(4-chlorophenyl)-4-[3-[4-[4-[[4-[[(2R)-4-(dimethylamino)-1-phenylsulfanylbutan-2-yl]amino]-3-nitrophenyl]sulfonylamino]phenyl]piperazin-1-yl]phenyl]-2-methyl-1-propan-2-ylpyrrole-3-carboxylic acid
• CAS: 1384513-01-2
• 化学式: C₄₉H₅₄ClN₇O₆S₂
• 分子量: 936.596
• InChiKey: NZOKTKRQBONDFO-LDLOPFEMSA-N

物化性质

• 沸点：
  998.6±75.0 °C(predicted)
• 密度：
  1.31±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  65
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  190
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  1-(4-硝基苯基)哌嗪 在 吡啶 、 copper(l) iodide 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 、 L-脯氨酸 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-5-(4-chlorophenyl)-4-(3-(4-(4-(4-(4-(dimethylamino)-1-(phenylthio)butan-2-ylamino)-3-nitrophenylsulfonamido)phenyl)piperazin-1-yl)phenyl)-1-isopropyl-2-methyl-1H-pyrrole-3-carboxylic acid
  参考文献：
  名称：

  Structure-Based Design of Potent Bcl-2/Bcl-xL Inhibitors with Strong in Vivo Antitumor Activity

  摘要：

  Bcl-2 and Bcl-xL are key apoptosis regulators and attractive cancer therapeutic targets. We have designed and optimized a class of small-molecule inhibitors of Bcl-2 and Bcl-xL containing a 4,5-diphenyl-1H-pyrrole-3-carboxylic acid core structure. A 1.4 angstrom resolution crystal structure of a lead compound, 12, complexed with Bcl-xL has provided a basis for our optimization. The most potent compounds, 14 and 15, bind to Bcl-2 and Bcl-xL with subnanomolar K-i values and are potent antagonists of Bcl-2 and Bcl-xL in functional assays. Compounds 14 and 15 inhibit cell growth with low nanomolar IC50 values in multiple small-cell lung cancer cell lines and induce robust apoptosis in cancer cells at concentrations as low as 10 nM. Compound 14 also achieves strong antitumor activity in an animal model of human cancer.

  DOI：

  10.1021/jm300608w

文献信息

• BCL-2/BCL-XL INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
  申请人：Wang Shaomeng

  公开号：US20120189539A1

  公开（公告）日：2012-07-26

  Inhibitors of Bcl-2/Bcl-xL and compositions containing the same are disclosed. Methods of using the Bcl-2/Bcl-xL inhibitors in the treatment of diseases and conditions wherein inhibition of Bcl-2/Bcl-xL provides a benefit, like cancers, also are disclosed.

  本文披露了Bcl-2/Bcl-xL抑制剂及其组合物。还披露了使用Bcl-2/Bcl-xL抑制剂治疗疾病和病况的方法，其中抑制Bcl-2/Bcl-xL会带来益处，例如癌症等。
• COMPOSITIONS FOR USE IN THE TREATMENT OF SENESCENCE-ASSIOCATED DISEASE AND DISORDERS
  申请人：Buck Institute for Research on Aging

  公开号：EP3669881A1

  公开（公告）日：2020-06-24

  Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.

  本文提供了选择性杀死衰老细胞和通过施用衰老分解剂治疗衰老相关疾病和紊乱的方法。可通过使用本文所述衰老分解剂的方法治疗的衰老相关疾病和失调包括与动脉硬化相关或由动脉硬化引起的心血管疾病和失调，如动脉粥样硬化；特发性肺纤维化；慢性阻塞性肺病；骨关节炎；衰老相关眼科疾病和失调；以及衰老相关皮肤病和失调。
• Treatment of ophthalmic conditions by selectively removing senescent cells from the eye
  申请人：Buck Institute for Research on Aging

  公开号：US10010546B2

  公开（公告）日：2018-07-03

  Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.

  本文提供了选择性杀死衰老细胞和通过施用衰老分解剂治疗衰老相关疾病和紊乱的方法。可通过使用本文所述衰老分解剂的方法治疗的衰老相关疾病和失调包括与动脉硬化相关或由动脉硬化引起的心血管疾病和失调，如动脉粥样硬化；特发性肺纤维化；慢性阻塞性肺病；骨关节炎；衰老相关眼科疾病和失调；以及衰老相关皮肤病和失调。
• Treating pulmonary conditions by selectively removing senescent cells from the lung using an intermittent dosing regimen
  申请人：Buck Institute for Research on Aging

  公开号：US10258618B2

  公开（公告）日：2019-04-16

  Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.

  本文提供了选择性杀死衰老细胞和通过施用衰老分解剂治疗衰老相关疾病和紊乱的方法。可通过使用本文所述衰老分解剂的方法治疗的衰老相关疾病和失调包括与动脉硬化相关或由动脉硬化引起的心血管疾病和失调，如动脉粥样硬化；特发性肺纤维化；慢性阻塞性肺病；骨关节炎；衰老相关眼科疾病和失调；以及衰老相关皮肤病和失调。
• Use of sulfonamide inhibitors of BCL-2 and BCL-xL to treat ophthalmic disease by selectively removing senescent cells
  申请人：Unity Biotechnology, Inc.

  公开号：US10328073B2

  公开（公告）日：2019-06-25

  Methods are provided herein for selectively killing senescent cells and for treating senescence-associated diseases and disorders by administering a senolytic agent. Senescence-associated diseases and disorders treatable by the methods using the senolytic agents described herein include cardiovascular diseases and disorders associated with or caused by arteriosclerosis, such as atherosclerosis; idiopathic pulmonary fibrosis; chronic obstructive pulmonary disease; osteoarthritis; senescence-associated ophthalmic diseases and disorders; and senescence-associated dermatological diseases and disorders.

  本文提供了选择性杀死衰老细胞和通过施用衰老分解剂治疗衰老相关疾病和紊乱的方法。可通过使用本文所述衰老分解剂的方法治疗的衰老相关疾病和失调包括与动脉硬化相关或由动脉硬化引起的心血管疾病和失调，如动脉粥样硬化；特发性肺纤维化；慢性阻塞性肺病；骨关节炎；衰老相关眼科疾病和失调；以及衰老相关皮肤病和失调。