N-[4-[4-[3-[2-(4-Chlorophenyl)-5-methyl-1-(1-methylethyl)-4-(methylsulfonyl)-1H-pyrrol-3-yl]-5-fluorophenyl]-1-piperazinyl]phenyl]-4-[[(1R)-3-(4-hydroxy-1-piperidinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoro-methyl)sulfonyl]-benzenesulfonamide | 1391107-89-3

• 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: N-[4-[4-[3-[2-(4-Chlorophenyl)-5-methyl-1-(1-methylethyl)-4-(methylsulfonyl)-1H-pyrrol-3-yl]-5-fluorophenyl]-1-piperazinyl]phenyl]-4-[[(1R)-3-(4-hydroxy-1-piperidinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoro-methyl)sulfonyl]-benzenesulfonamide
• 英文别名: (R)-N-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-(methylsulfonyl)-1H-pyrrol-3-yl)-5-fluorophenyl)piperazin-1-yl)phenyl)-4-((4-(4-hydroxypiperidin-1-yl)-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide；(R)-N-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-(methylsulfonyl)-1H-pyrrol-3-yl)-5-fluorophenyl)piperazin-1-yl)phenyl)-4-((4-(4-hydroxypiperidin-1-yl)-1-(phenylthio)but-2-yl)amino)-3-((trifluoromethyl)sulfonyl)benzenesulfonamide；(3R)-1-(3-(4-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrol-3-yl)-5-fluorophenyl)piperazin-1-yl)-phenylaminosulfonyl)-2-trifluoromethylsulfonyl-anilino)-4-phenylthio-butyl)-4-hydroxyl-piperidine；N-[4-[4-[3-[2-(4-chlorophenyl)-5-methyl-4-methylsulfonyl-1-propan-2-ylpyrrol-3-yl]-5-fluorophenyl]piperazin-1-yl]phenyl]-4-[[(2R)-4-(4-hydroxypiperidin-1-yl)-1-phenylsulfanylbutan-2-yl]amino]-3-(trifluoromethylsulfonyl)benzenesulfonamide
• CAS: 1391107-89-3
• 化学式: C₅₃H₅₉ClF₄N₆O₇S₄
• 分子量: 1131.8
• InChiKey: DMKVQMFONHHNMZ-HUESYALOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.8
• 重原子数：
  75
• 可旋转键数：
  18
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  212
• 氢给体数：
  3
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  N-[4-[4-[3-[2-(4-Chlorophenyl)-5-methyl-1-(1-methylethyl)-4-(methylsulfonyl)-1H-pyrrol-3-yl]-5-fluorophenyl]-1-piperazinyl]phenyl]-4-[[(1R)-3-(4-hydroxy-1-piperidinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoro-methyl)sulfonyl]-benzenesulfonamide 、 FMOC-甘氨酸羟基琥珀酰亚胺酯 在 二乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 以83 mg的产率得到(R)-1-(3-(4-(N-(4-(4-(3-(2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-(methylsulfonyl)-1H-pyrrol-3-yl)-5-fluorophenyl)piperazin-1-yl)phenyl)sulfamoyl)-2-(trifluoromethylsulfonyl)phenylamino)-4-(phenylthio)butyl)piperidin-4-yl 2-aminoacetate
  参考文献：
  名称：

  BCL-2/BCL-XL INHIBITORS AND THERAPEUTIC METHODS USING THE SAME

  摘要：

  抑制剂Bcl-2/Bcl-xL及含有该抑制剂的组合物已被披露。还披露了在治疗需要抑制Bcl-2/Bcl-xL以获益的疾病和状况中使用Bcl-2/Bcl-xL抑制剂的方法，如癌症。

  公开号：

  US20140199234A1
• 作为产物：
  描述：

  3-溴-5-氟苯甲醛 在 哌啶 、 吡啶 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 1.2-[(2,6-二甲基苯基)氨基]-2-氧代-乙酸 、 水 、 铁粉 、 3-乙基-5-(2-羟乙基)-4-甲基噻唑溴化物 、 potassium carbonate 、 氯化铵 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 L-脯氨酸 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 1.0h， 生成 N-[4-[4-[3-[2-(4-Chlorophenyl)-5-methyl-1-(1-methylethyl)-4-(methylsulfonyl)-1H-pyrrol-3-yl]-5-fluorophenyl]-1-piperazinyl]phenyl]-4-[[(1R)-3-(4-hydroxy-1-piperidinyl)-1-[(phenylthio)methyl]propyl]amino]-3-[(trifluoro-methyl)sulfonyl]-benzenesulfonamide
  参考文献：
  名称：

  [EN] METHOD FOR PREPARING SULFONAMIDES DRUGS
  [FR] PROCÉDÉ DE PRÉPARATION DE MÉDICAMENTS À BASE DE SULFONAMIDES

  摘要：

  提供了一种制备Bcl-2/Bcl-xL抑制剂磺胺类化合物的方法，包括化合物(3R)-1-(3-(4-(4-(4-(3-(2-(4-氯苯基)-1-异丙基-4-甲基磺酰基-5-甲基-1H-吡咯-3-基)-5-氟苯基)哌嗪-1-基)-苯基氨基磺酰基)-2-三氟甲基磺酰基苯胺基)-4-苯硫醚丁基)-4-羟基哌嗪。还提供了制备磺胺类化合物的中间体，新的最终产品及其治疗用途，以及药用途。

  公开号：

  WO2020140957A1

文献信息

• [EN] COMPOUNDS THAT INDUCE DEGRADATION OF ANTI-APOPTOTIC BCL-2 FAMILY PROTEINS AND THE USES THEREOF<br/>[FR] COMPOSÉS INDUISANT LA DÉGRADATION DE PROTÉINES ANTI-APOPTOTIQUES DE LA FAMILLE BCL-2 ET UTILISATION DE CES DERNIERS
  申请人：BIOVENTURES LLC

  公开号：WO2017184995A1

  公开（公告）日：2017-10-26

  The present disclosure provides compositions and methods for selectively killing senescent cells, wherein the composition comprises a compound of Formula (I) or a compound of Formula (II). The selective killing of senescent cells may delay aging and/or treat age-related disorders.

  本公开提供了一种用于选择性杀灭衰老细胞的组合物和方法，其中该组合物包括式(I)的化合物或式(II)的化合物。对衰老细胞的选择性杀灭可能延缓衰老和/或治疗与年龄相关的疾病。
• [EN] NEW ANTICANCER DRUG COMBINATIONS<br/>[FR] NOUVELLES COMBINAISONS DE MÉDICAMENTS ANTICANCÉREUX
  申请人：FUNDACION PARA LA INVESTIG MEDICA APLICADA

  公开号：WO2019243236A1

  公开（公告）日：2019-12-26

  It relates to a combination comprising: A) a compound of formula (I), or a pharmaceutically or veterinary acceptable salt thereof, or any stereoisomer or mixtures of stereoisomers, either of the compound of formula (I) or of any of its pharmaceutically or veterinary acceptable salts, wherein L, X, R1, R2, R3, and R4 are as defined herein; and B) a drug selected from the group consisting of: i) an immune checkpoint inhibitor, ii) an inhibitor of an anti-apoptotic protein, and iii) a chemotherapeutic agent other than an inhibitor of an anti-apoptotic protein and an immune checkpoint inhibitor; and to pharmaceutical or veterinary compositions, and package or kit of parts comprising it. It also relates to the combination, the composition or a package or kit of parts for use in the treatment and/or prevention of cancer.

  它涉及到一种组合物，包括：A）式（I）的化合物，或其药学或兽医上可接受的盐，或者是式（I）的化合物或其药学或兽医上可接受的盐的任何立体异构体或立体异构体混合物，其中L，X，R1，R2，R3和R4如本文所定义；和B）从以下组中选择的药物：i）免疫检查点抑制剂，ii）抗凋亡蛋白的抑制剂，和iii）化疗药物，除了抗凋亡蛋白的抑制剂和免疫检查点抑制剂之外的化疗药物；以及用于治疗和/或预防癌症的药物或兽医组合物、包装或配件套件。它还涉及到该组合物、组合物或包装或配件套件，用于治疗和/或预防癌症。
• 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。
• Compositions of matter for treatment of ophthalmic conditions by selectively removing senescent cells from the eye
  申请人：Buck Institute for Research on Aging

  公开号：US10478432B2

  公开（公告）日：2019-11-19

  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。
• Unit dose of an aryl sulfonamide that is effective for treating eye disease and averting potential vision loss
  申请人：Unity Biotechnology, Inc.

  公开号：US10478433B2

  公开（公告）日：2019-11-19

  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。