4-氨基苯甲-2,6-D2酸 | 118872-62-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氨基苯甲-2,6-D2酸
• 英文名称: 4-Amino-benzoesaeure-2,6-d(2)
• 英文别名: para-Aminobenzoesaeure-<2,6-d>；4-amino-2,6-dideuterio-benzoic acid；4-Aminobenzoic-2,6-D2 acid；4-amino-2,6-dideuteriobenzoic acid
• CAS: 118872-62-1
• 化学式: C₇H₇NO₂
• 分子量: 139.122
• InChiKey: ALYNCZNDIQEVRV-QDNHWIQGSA-N

物化性质

• 熔点：
  186-186.5 °C

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  对氨基苯甲酸 在 (1,5-COD)Ir(I)-1,1,1,5,5,5-hexafluoropentan-2,4-dionate 重水 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 4.0h， 生成 4-氨基苯甲-2,6-D2酸
  参考文献：
  名称：

  Labelling of anilines, benzylamines and someN-heterocyclics using cycloocta-1,5-dienyliridium(I)-1,1,1,5,5,5-hexafluoro-pentan-2,4-dionate and isotopic hydrogen gas in DMF or DMA

  摘要：

  各种各样的苯胺、苄胺以及一些N-杂环化合物可以在室温下使用氘气和环辛-1,5-二烯基铱(I)-1,1,1,5,5,5-六氟戊酸-2,4-二酮在DMF或DMA中进行邻位氘化。该方法适用于氚标记。版权 © 2004 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.898

文献信息

• Convenient and efficient deuteration of functionalized aromatics with deuterium oxide: catalysis by cycloocta-1,5-dienyliridium(I) 1,3-dionates
  作者：B. McAuley、M. J. Hickey、L. P. Kingston、J. R. Jones、W. J. S. Lockley、A. N. Mather、E. Spink、S. P. Thompson、D. J. Wilkinson

  DOI：10.1002/jlcr.780

  日期：2003.11

  Aromatic compounds bearing an ortho-directing substituent may be deuterated by exchange with deuterium oxide in the presence of a range of cycloocta-1,5-dienyliridium(I)1,3-dionate catalysts. The exchange takes place in several dipolar aprotic solvents and is directly applicable to the deuteration of polar compounds. Isotope incorporation is efficient and regiospecific. The method is applicable to a wide range of ortho-directing groups some of which are only weak directors for alternative ortho-labelling approaches. In addition, the application of microwaves enables labelling within minutes even with sub-stituents which are poor directors. Copyright © 2003 John Wiley & Sons, Ltd.

  具有邻位导向取代基的芳香化合物可在多种环辛二烯基铱(I)1,3-二酮催化剂的存在下，通过与重水交换实现氘代。该交换过程可在多种偶极非质子溶剂中进行，并可直接应用于极性化合物的氘代。同位素掺入效率高且区域选择性强。该方法适用于多种邻位导向基团，其中一些基团对于其他邻位标记方法仅具有较弱的导向作用。此外，微波的应用使得即使对于导向作用较弱的取代基，也能在几分钟内完成标记。版权所有 © 2003 John Wiley & Sons, Ltd.
• Labelling of anilines, benzylamines and someN-heterocyclics using cycloocta-1,5-dienyliridium(I)-1,1,1,5,5,5-hexafluoro-pentan-2,4-dionate and isotopic hydrogen gas in DMF or DMA
  作者：R. N. Garman、M. J. Hickey、L. P. Kingston、B. McAuley、J. R. Jones、W. J. S. Lockley、A. N. Mather、D. J. Wilkinson

  DOI：10.1002/jlcr.898

  日期：2005.1

  A wide range of anilines, benzylamines and some N-heterocyclics can be ortho-deuterated at room temperature using deuterium gas and cycloocta-1,5-dienyliridium(I)-1,1,1,5,5,5-hexafluoropentan-2,4-dionate in DMF or DMA. The method is applicable to labelling with tritium. Copyright © 2004 John Wiley & Sons, Ltd.

  各种各样的苯胺、苄胺以及一些N-杂环化合物可以在室温下使用氘气和环辛-1,5-二烯基铱(I)-1,1,1,5,5,5-六氟戊酸-2,4-二酮在DMF或DMA中进行邻位氘化。该方法适用于氚标记。版权 © 2004 John Wiley & Sons, Ltd.
• FAK inhibitor and drug combination thereof
  申请人：HINOVA PHARMACEUTICALS INC.

  公开号：US20220125788A1

  公开（公告）日：2022-04-28

  A deuterated compound as represented by formula (I) or an optical isomer, a tautomer, a pharmaceutically acceptable salt, a prodrug, a hydrate, or a solvate thereof are presented. Compared with a compound before deuteration, the deuterated compound shows better pharmacokinetics, higher maximum plasma drug concentration, higher exposure, and longer half-life, and has more excellent metabolic performance. The deuterated compound can effectively inhibit FAK activity, and has good application prospect in preparation of FAK inhibitors and/or drugs for treating cancer. In addition, the use of the deuterated compound in combination with an anti-cancer drug (such as a PD-1 inhibitor) can achieve a synergistic effect, thereby significantly improving the tumor suppression effect, and providing a better choice for clinical cancer treatment.

  本发明提供了由公式(I)所表示的氘代化合物或其光学异构体、互变异构体、药学上可接受的盐、前药、水合物或溶剂化物。与氘代化合物之前的化合物相比，氘代化合物表现出更好的药代动力学、更高的最大血浆药物浓度、更高的曝光度和更长的半衰期，并具有更出色的代谢性能。氘代化合物可以有效地抑制FAK活性，在制备FAK抑制剂和/或用于治疗癌症的药物方面具有良好的应用前景。此外，将氘代化合物与抗癌药物（如PD-1抑制剂）联合使用可以实现协同作用，从而显著提高肿瘤抑制效果，为临床癌症治疗提供更好的选择。
• DEUTERATED DEFACTINIB COMPOUND AND USE THEREOF
  申请人：Hinova Pharmaceuticals Inc.

  公开号：EP3792257A1

  公开（公告）日：2021-03-17

  Provided are a compound as shown in formula (I) or optical isomers, pharmaceutically acceptable salts, hydrates or solvates thereof, wherein R1-RI8 are independently selected from hydrogen and deuterium respectively, but not all of them are hydrogen at the same time. The compound and salts, hydrates or solvates thereof can be used as FAK inhibitors, and used in the preparation of anti-cancer drugs, and compared with the non-deuterated control compound Defactinib, the compound has significantly improved metabolic stability and pharmacokinetic properties, while also possessing good application prospects.

  提供了一种如式（I）所示的化合物或其光学异构体、药学上可接受的盐、水合物或溶液，其中R1-RI8分别独立地选自氢和氘，但并非同时都是氢。该化合物及其盐、水合物或溶物可作为FAK抑制剂，用于制备抗癌药物，与非氘代对照化合物Defactinib相比，该化合物的代谢稳定性和药代动力学特性显著提高，同时也具有良好的应用前景。
• FAK INHIBITOR AND DRUG COMBINATION THEREOF
  申请人：Hinova Pharmaceuticals Inc.

  公开号：EP3904351A1

  公开（公告）日：2021-11-03

  A deuterated compound as represented by formula (I) or an optical isomer, a tautomer, a pharmaceutically acceptable salt, a prodrug, a hydrate, or a solvate thereof. Compared with a compound before deuteration, the deuterated compound shows better pharmacokinetics, higher maximum plasma drug concentration, higher exposure, and longer half-life, and has more excellent metabolic performance. Moreover, the deuterated compound can effectively inhibit FAK activity, and has good application prospect in preparation of FAK inhibitors and/or drugs for treating cancer. In addition, the use of the deuterated compound in combination with an anti-cancer drug (such as a PD-1 inhibitor) can achieve a synergistic effect, thereby significantly improving the tumor suppression effect, and providing a better choice for clinical cancer treatment.

  由式（I）表示的氚代化合物或其光学异构体、同分异构体、药学上可接受的盐、原药、水合物或溶液。与氚化前的化合物相比，氚化后的化合物显示出更好的药代动力学、更高的最大血浆药物浓度、更高的暴露量和更长的半衰期，并具有更优异的代谢性能。此外，氚代化合物能有效抑制 FAK 活性，在制备 FAK 抑制剂和/或治疗癌症的药物方面具有良好的应用前景。此外，氘代化合物与抗癌药物（如PD-1抑制剂）联合使用，可以达到协同增效的效果，从而显著提高抑瘤效果，为临床癌症治疗提供了更好的选择。