1-[3-[2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-methylsulfonyl-pyrrol-3-yl]-5-fluoro-phenyl]-4-(4-nitrophenyl)piperazine | 1619923-52-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-[3-[2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-methylsulfonyl-pyrrol-3-yl]-5-fluoro-phenyl]-4-(4-nitrophenyl)piperazine
• 英文别名: 1-[3-[2-(4-Chlorophenyl)-5-methyl-4-methylsulfonyl-1-propan-2-ylpyrrol-3-yl]-5-fluorophenyl]-4-(4-nitrophenyl)piperazine；1-[3-[2-(4-chlorophenyl)-5-methyl-4-methylsulfonyl-1-propan-2-ylpyrrol-3-yl]-5-fluorophenyl]-4-(4-nitrophenyl)piperazine
• CAS: 1619923-52-2
• 化学式: C₃₁H₃₂ClFN₄O₄S
• 分子量: 611.137
• InChiKey: QVRKXBYMAMJZNG-UHFFFAOYSA-N

物化性质

• 沸点：
  777.4±60.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  42
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[3-[2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-methylsulfonyl-pyrrol-3-yl]-5-fluoro-phenyl]-4-(4-nitrophenyl)piperazine 在 吡啶 、 水 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 25.0h， 生成 (R)-3-(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)piperidine-4-carbonyloxy)propylphosphonic acid
  参考文献：
  名称：

  一种制备磺胺类化合物的工艺

  摘要：

  本发明涉及一种制备磺胺类化合物的工艺，所述磺胺类化合物是Bcl‑2/Bcl‑xL的抑制剂，包括化合物(3R)‑1‑(3‑(4‑(4‑(4‑(3‑(2‑(4‑氯苯基)‑1‑异丙基‑4‑甲磺酰基‑5‑甲基‑1H‑吡咯‑3‑基)‑5‑氟苯基)哌嗪‑1‑基)‑苯氨基磺酰)‑2‑三氟甲磺酰基‑苯胺基)‑4‑苯硫基‑丁基)‑哌啶‑4‑羧酸3‑膦酸基丙酯。本发明还涉及用于制备所述磺胺类化合物的中间体及其制备方法。

  公开号：

  CN111410666B
• 作为产物：
  描述：

  3-溴-5-氟苯甲醛 在 哌啶 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 水 、 3-乙基-5-(2-羟乙基)-4-甲基噻唑溴化物 、 potassium carbonate 、 溶剂黄146 、 三乙胺 、 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 48.0h， 生成 1-[3-[2-(4-chlorophenyl)-1-isopropyl-5-methyl-4-methylsulfonyl-pyrrol-3-yl]-5-fluoro-phenyl]-4-(4-nitrophenyl)piperazine
  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] PROCESS FOR PREPARING SULFONAMIDE COMPOUNDS<br/>[FR] PROCÉDÉ DE PRÉPARATION DE COMPOSÉS DE SULFONAMIDE
  申请人：ASCENTAGE PHARMA SUZHOU CO LTD

  公开号：WO2020140956A1

  公开（公告）日：2020-07-09

  Provided are a process for preparing a sulfonamide compound which is an inhibitor of Bcl-2/Bcl-xL, including the compound (3R) -1- (3- (4- (4- (4- (3- (2- (4-chlorophenyl) -1-isopropyl-4-methylsulfonyl-5-methyl-1H-pyrrol-3-yl) -5-fluorophenyl) piperazine -1-yl) -phenylaminosulfonyl) -2-trifluoromethanesulfonyl-anilino) -4-ph enylthio-butyl) -piperidine-4-carboxylic acid 3-phosphonopropyl ester, an intermediate for preparing the sulfonamide compound and a preparation process thereof.

  提供了一种制备硫酰胺化合物的过程，该化合物是Bcl-2/Bcl-xL的抑制剂，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)-苯胺磺酰基)-2-三氟甲磺酰基苯胺基)-4-苯硫基-丁基)-哌啶-4-羧酸3-磷酸丙基酯，用于制备硫酰胺化合物的中间体及其制备过程。
• BCL-2/BCL-XL INHIBITORS AND THERAPEUTIC METHODS USING THE SAME
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US20140199234A1

  公开（公告）日：2014-07-17

  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.

  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。
• Phospholidines that are Bcl Family Antagonists for Use in Clinical Management of Conditions Caused or Mediated By Senescent Cells and for Treating Cancer
  申请人：Unity Biotechnology

  公开号：US20190330250A1

  公开（公告）日：2019-10-31

  This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold. The phospholidine compounds can include a P-phenyl phospholidine moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phospholidine moiety can be optionally substituted at phosphorus with thio (═S) instead of oxo (═O). A second heteroatom attached to phosphorus can be cyclically linked to the N-substituted nitrogen atom of the phospholidine that is attached to the phosphorus to provide, together with the phosphorus atom through which they are connected, a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety a favorable binding conformation can be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

  本公开提供了具有Bcl抑制活性的化合物，其基于一种新的化学骨架。磷脂胺化合物可以包括一个P-苯基磷脂胺基团，该基团被N-芳基或N-杂环芳基取代。P-苯基磷脂胺基团可以选择性地在磷上用硫（═S）代替氧（═O）进行取代。连接到磷的第二个杂原子可以与连接到磷的磷脂胺的N-取代氮原子形成环状连接，从而与它们通过连接的磷原子一起提供一个杂环环。通过在核心连接基团的两个磷取代物之间引入这样的环状约束，可以促进化合物中的有利结合构象。选择的化合物促进老化细胞中的凋亡，并可用于治疗与老化相关的疾病，如骨关节炎、眼科疾病、肺部疾病和动脉粥样硬化。选择的化合物促进癌细胞中的凋亡，并可作为化疗药物进行开发。
• Phosphonamidates that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
  申请人：Unity Biotechnology

  公开号：US10738042B2

  公开（公告）日：2020-08-11

  This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold, as shown in Formula (I): Phosphonamidate compounds disclosed herein typically include a P-phenyl phosphonamidate moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phosphonamidate moiety may be optionally substituted at phosphorus with thio (═S) instead of oxo (═O), and/or with a thioxy group or a second amino group instead of an oxy group. One of the heteroatoms attached to phosphorus may be cyclically linked to the N-substituted nitrogen atom that is attached to the phosphorus to provide a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety, a favorable binding conformation may be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

  本公开提供了基于新化学支架的具有 Bcl 抑制活性的化合物，如式 (I) 所示： 本文公开的膦酰胺化合物通常包括一个被 N-芳基或 N-杂芳基取代的 P-苯基膦酰胺分子。P-苯基膦甲酰胺基团可任选被硫代（═S）取代氧代（═O），和/或被硫氧基团或第二氨基取代氧基团。与磷相连的杂原子之一可与与磷相连的 N-取代的氮原子环状连接，形成杂环。通过在核心连接分子的两个磷取代基之间加入这种环状约束，可促进化合物形成有利的结合构象。所选化合物可促进衰老细胞的凋亡，并可开发用于治疗与衰老有关的疾病，如骨关节炎、眼科疾病、肺部疾病和动脉粥样硬化。精选化合物能促进癌细胞凋亡，可开发为化疗药物。
• Phospholidines that are Bcl family antagonists for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer
  申请人：Unity Biotechnology, Inc.

  公开号：US10745429B2

  公开（公告）日：2020-08-18

  This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold, as shown in Formula (I). The phospholidine compounds can include a P-phenyl phospholidine moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phospholidine moiety can be optionally substituted at phosphorus with thio (═S) instead of oxo (═O). A second heteroatom attached to phosphorus can be cyclically linked to the N-substituted nitrogen atom of the phospholidine that is attached to the phosphorus to provide, together with the phosphorus atom through which they are connected, a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety a favorable binding conformation can be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

  本公开提供了基于新化学支架的具有 Bcl 抑制活性的化合物，如式 (I) 所示。 膦啶化合物可以包括一个被 N-芳基或 N-杂芳基取代的 P-苯基膦啶分子。P-苯基膦烷分子可以任选被硫代（═S）而不是氧代（═O）取代。连接到磷上的第二个杂原子可以与连接到磷上的磷苷的 N-取代的氮原子循环连接，从而与通过它们连接的磷原子一起形成一个杂环。通过在核心连接分子的两个磷取代基之间加入这种环状约束，可以促进化合物形成有利的结合构象。所选化合物能促进衰老细胞的凋亡，可开发用于治疗与衰老有关的疾病，如骨关节炎、眼科疾病、肺部疾病和动脉粥样硬化。精选化合物能促进癌细胞凋亡，可开发为化疗药物。