N-[(R)-(1H-indol-3-yl)(2-vinylphenyl)methyl]-C-phenylmethanesulfonamide | 1123755-06-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: N-[(R)-(1H-indol-3-yl)(2-vinylphenyl)methyl]-C-phenylmethanesulfonamide
• 英文别名: N-[(R)-(2-ethenylphenyl)-(1H-indol-3-yl)methyl]-1-phenylmethanesulfonamide
• CAS: 1123755-06-5
• 化学式: C₂₄H₂₂N₂O₂S
• 分子量: 402.517
• InChiKey: QWOBUJPQDUUHPW-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  70.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[(R)-(1H-indol-3-yl)(2-vinylphenyl)methyl]-C-phenylmethanesulfonamide 在 2,6-二甲基吡啶 、 甲醇 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 乙腈 、 叔丁醇 为溶剂， 反应 1.17h， 生成 (R)-3-(2-(benzylsulfonyl)isoindolin-1-yl)-1H-indole
  参考文献：
  名称：

  Synthesis, molecular modeling, and biological evaluation of novel RAD51 inhibitors

  摘要：

  RAD51 recombinase plays a critical role for cancer cell proliferation and survival. Targeting RAD51 is therefore an attractive strategy for treating difficult-to-treat cancers, e.g. triple negative breast cancers which are often resistant to existing therapeutics. To this end, we have designed, synthesized and evaluated a panel of new RAD51 inhibitors, denoted IBR compounds. Among these compounds, we have identified a novel small molecule RAD51 inhibitor, IBR120, which exhibited a 4.8-fold improved growth inhibition activity in triple negative human breast cancer cell line MBA-MD-468. IBR120 also inhibited the proliferation of a broad spectrum of other cancer cell types. Approximately 10-fold difference between the IC50 values in normal and cancer cells were observed. Moreover, IBR120 was capable of disrupting RAD51 multimerization, impairing homologous recombination repair, and inducing apoptotic cell death. Therefore, these novel RAD51 inhibitors may serve as potential candidates for the development of pharmaceutical strategies against difficult-to-treat cancers. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.021
• 作为产物：
  描述：

  吲哚 、 N-[(2-ethenylphenyl)methylidene]-1-phenylmethanesulfonamide 在 N-[3,5-双(三氟甲基)苯基]-N′-[(9R)-6′-甲氧基-9-金鸡宁]硫脲 作用下， 以 乙酸乙酯 为溶剂， 反应 288.0h， 以55%的产率得到N-[(R)-(1H-indol-3-yl)(2-vinylphenyl)methyl]-C-phenylmethanesulfonamide
  参考文献：
  名称：

  Stereoselective Synthesis of Chiral IBR2 Analogues

  摘要：

  Two stereoselective routes were developed to synthesize optically pure IBR2 analogues 1-16. The first features addition of N-Boc-3-bromoindole 26 to the sulfinamide 25, providing a 1: 1 ratio of the separable diasteroisomers 27 and 28 in good yield. In a straightforward fashion, the sulfinamides 27 and 28 were conveniently converted into the key amines 39 and 47 over 8 steps, respectively, from which a series of 3,4-dihydroisoquinolinyl IBR2 analogues 1-14 containing fluorinated and trifluoromethylated benzyl groups were prepared. Another route highlights the highly enantioselective addition of indole to the sulfonyl amide 50 with bifunctional aminothioureas 57 and 58 as catalysts. After the reaction conditions were optimized, the desired sulfonyl amides (R)-55 and (S)-55 were obtained in 99% ee and 98% ee, respectively. Acylation of (R)-55 and (S)-55 separately and subsequent allylation gave compounds 60 and 63, respectively, which were further subjected to RCM to furnish compounds 61 and 64 and, after removal of the Boc groups, the desired IBR2 analogues 15 and 16.

  DOI：

  10.1021/jo802607f

文献信息

• RAD51 inhibitors and uses thereof
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US10421753B2

  公开（公告）日：2019-09-24

  The present invention includes novel RAD51 inhibitors. The compounds of the invention may be useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.

  本发明包括新型 RAD51 抑制剂。本发明的化合物可用于预防或治疗有需要的受试者的癌症。本发明还包括通过向有需要的受试者施用治疗有效量的本发明化合物来预防或治疗癌症的方法。
• Stereoselective Synthesis of Chiral IBR2 Analogues
  作者：Xiao-Long Qiu、Jiewen Zhu、Guikai Wu、Wen-Hwa Lee、A. Richard Chamberlin

  DOI：10.1021/jo802607f

  日期：2009.3.6

  Two stereoselective routes were developed to synthesize optically pure IBR2 analogues 1-16. The first features addition of N-Boc-3-bromoindole 26 to the sulfinamide 25, providing a 1: 1 ratio of the separable diasteroisomers 27 and 28 in good yield. In a straightforward fashion, the sulfinamides 27 and 28 were conveniently converted into the key amines 39 and 47 over 8 steps, respectively, from which a series of 3,4-dihydroisoquinolinyl IBR2 analogues 1-14 containing fluorinated and trifluoromethylated benzyl groups were prepared. Another route highlights the highly enantioselective addition of indole to the sulfonyl amide 50 with bifunctional aminothioureas 57 and 58 as catalysts. After the reaction conditions were optimized, the desired sulfonyl amides (R)-55 and (S)-55 were obtained in 99% ee and 98% ee, respectively. Acylation of (R)-55 and (S)-55 separately and subsequent allylation gave compounds 60 and 63, respectively, which were further subjected to RCM to furnish compounds 61 and 64 and, after removal of the Boc groups, the desired IBR2 analogues 15 and 16.
• Synthesis, molecular modeling, and biological evaluation of novel RAD51 inhibitors
  作者：Jiewen Zhu、Hongyuan Chen、Xuning Emily Guo、Xiao-Long Qiu、Chun-Mei Hu、A. Richard Chamberlin、Wen-Hwa Lee

  DOI：10.1016/j.ejmech.2015.04.021

  日期：2015.5

  RAD51 recombinase plays a critical role for cancer cell proliferation and survival. Targeting RAD51 is therefore an attractive strategy for treating difficult-to-treat cancers, e.g. triple negative breast cancers which are often resistant to existing therapeutics. To this end, we have designed, synthesized and evaluated a panel of new RAD51 inhibitors, denoted IBR compounds. Among these compounds, we have identified a novel small molecule RAD51 inhibitor, IBR120, which exhibited a 4.8-fold improved growth inhibition activity in triple negative human breast cancer cell line MBA-MD-468. IBR120 also inhibited the proliferation of a broad spectrum of other cancer cell types. Approximately 10-fold difference between the IC50 values in normal and cancer cells were observed. Moreover, IBR120 was capable of disrupting RAD51 multimerization, impairing homologous recombination repair, and inducing apoptotic cell death. Therefore, these novel RAD51 inhibitors may serve as potential candidates for the development of pharmaceutical strategies against difficult-to-treat cancers. (C) 2015 Elsevier Masson SAS. All rights reserved.