2-hydroxy-4-trifluoromethanesulfonyloxybenzoic acid methyl ester | 149878-72-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-hydroxy-4-trifluoromethanesulfonyloxybenzoic acid methyl ester
• 英文别名: methyl 2-hydroxy-4-(trifluoromethansulfonyloxy)benzoate；methyl 2-hydroxy-4-(trifluoromethanesulfonyloxy)benzoate；Methyl 2-hydroxy-4-(trifluoromethylsulfonyloxy)benzoate
• CAS: 149878-72-8
• 化学式: C₉H₇F₃O₆S
• 分子量: 300.212
• InChiKey: LYVGIMUOQBGZJC-UHFFFAOYSA-N

物化性质

• 熔点：
  91.5-92 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  353.1±42.0 °C(Predicted)
• 密度：
  1.603±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  98.3
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-hydroxy-4-trifluoromethanesulfonyloxybenzoic acid methyl ester 在 四(三苯基膦)钯 、 三氟甲磺酸酐 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 正己烷 、 二氯甲烷 为溶剂， 反应 96.0h， 生成 2-morpholin-4-yl-7-thiophen-2-ylchromen-4-one
  参考文献：
  名称：

  Discovery of Potent Chromen-4-one Inhibitors of the DNA-Dependent Protein Kinase (DNA-PK) Using a Small-Molecule Library Approach

  摘要：

  Structure-activity relationships for inhibition of DNA-dependent protein kinase (DNA-PK) have been defined for substituted chromen-4-ones. For the 2-amino-substituted benzo[h]chromen-4-ones, a morpholine substituent at this position was essential for activity. Small libraries of 6- and 7-alkoxy-substituted chromen-4-ones showed that a number of 7-alkoxysubstituted chromenones displayed improved activity. Focused libraries incorporating 6-, 7-, and 8-aryl and heteroaryl substituents were prepared. In these cases, 6- and 7-substitution was disfavored, whereas 8-substitution was largely tolerated. Surprisingly, two compounds, 2-N-morpholino-8-dibenzofuranyl-chromen-4-one (NU7427, 32{38}) and the 2-N-morpholino-8-dibenzothiophenyl-chromen-4-one (NU7441, 32{26}) were excellent inhibitors (IC50 vs DNAPK = 40 and 13 nM, respectively). The ring-saturated analogue 2-N-morpholino-8-(6',7',8',9'-tetrahydrodibenzothiophene)chromen-4-one, 36, retained potent activity (IC50 vs DNA-PK = 23 nM). The dibenzothiophene 32{38} sensitized HeLa cells to ionizing radiation in vitro, with dose modification factors of 2.5 at 10% survival being observed at 0.5 mu M. The cytotoxicity of the topoisomerase II inhibitor etoposide was also potentiated.

  DOI：

  10.1021/jm050444b
• 作为产物：
  描述：

  2,4-二羟基苯甲酸 在 吡啶 、 4-二甲氨基吡啶 、 硫酸 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 2-hydroxy-4-trifluoromethanesulfonyloxybenzoic acid methyl ester
  参考文献：
  名称：

  吡唑并[1，5-a]嘧啶的优化导致鉴定出高度选择性的酪蛋白激酶2抑制剂。

  摘要：

  酪蛋白激酶2（CK2）是组成型表达的丝氨酸/苏氨酸激酶，具有大量的细胞底物。因此，CK2已经与多种调节功能相关，并且CK2的失调与疾病发展特别是与癌症有关。疾病病理学的广泛含义使CK2成为有吸引力的靶标。迄今为止，最先进的CK2抑制剂是silmitasertib，尽管已描述了silmitasertib的多个脱靶靶标，但已在临床试验中研究了silmitasertib。为了确定CK2抑制在癌症，其他疾病和正常生理中的作用，非常需要选择性CK2抑制剂的开发。在这项研究中，我们探索了吡唑并[1,5- a]嘧啶铰链结合部分用于开发选择性CK2抑制剂。该支架的优化（包括大环化）导致产生IC20（31），该化合物对CK2表现出较高的体外效力（K D  = 12 nM），对CK2的排他选择性更高。X射线分析揭示了IC20的典型I型结合模式（31）。但是，效力需要许多CK2抑制剂（包括silmitasert

  DOI：

  10.1016/j.ejmech.2020.112770

文献信息

• [EN] MACROCYCLIC FLT3 KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASE FLT3 MACROCYCLIQUES
  申请人：ONCODESIGN SA

  公开号：WO2013045653A1

  公开（公告）日：2013-04-04

  The present invention relates to macrocylic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of FLT3 (FMS-Related Tyrosine kinase 3). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the treatment of cell proliferative disorders, such as cancer.

  本发明涉及大环化合物以及含有作为激酶抑制剂，特别是FLT3（FMS相关酪氨酸激酶3）抑制剂的所述化合物的组合物。此外，本发明还提供了所述化合物的制备过程，以及使用它们的方法，例如作为药物，特别用于治疗细胞增殖紊乱，如癌症。
• MACROCYCLIC FLT3 KINASE INHIBITORS
  申请人：ONCODESIGN S.A.

  公开号：US20140303159A1

  公开（公告）日：2014-10-09

  The present invention relates to macrocylic compounds and compositions containing said compounds acting as kinase inhibitors, in particular as inhibitors of FLT3 (FMS-Related Tyrosine kinase 3). Moreover, the present invention provides processes for the preparation of the disclosed compounds, as well as methods of using them, for instance as a medicine, in particular for the treatment of cell proliferative disorders, such as cancer.

  本发明涉及大环化合物以及含有作为激酶抑制剂，特别是FLT3（FMS相关酪氨酸激酶3）抑制剂的所述化合物的组合物。此外，本发明还提供了所述化合物的制备过程，以及使用它们的方法，例如作为药物，特别用于治疗细胞增殖紊乱，如癌症。
• [EN] DNA-PK INHIBITORS<br/>[FR] INHIBITEURS D'ADN-PK
  申请人：CANCER REC TECH LTD

  公开号：WO2003024949A1

  公开（公告）日：2003-03-27

  The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein R?1 and R2¿ are independently hydrogen, an optionally substituted C¿1-7? alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; X and Y are selected from CR?4¿ and O, O and CR'4 and NR'4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R?3 and R4 or R'4¿ is an optionally substituted C¿3-20? heteroaryl or C5-20 aryl group, and the other of R?3 and R4 or R'4¿ is H, or R?3 and R4 or R'4¿ together are -A-B-, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM.

  本发明涉及使用式(I)化合物及其异构体、盐、溶剂合物、化学保护形式和前药，在制备用于抑制DNA-PK活性的药物中使用，其中R?1和R2¿分别为氢、可选取代的C¿1-7?烷基、C3-20杂环基或C5-20芳基，或者可以与它们连接的氮原子一起形成具有4到8个环原子的可选取代杂环环；X和Y从CR?4¿和O、O和CR'4和NR'4和N中选取，其中不饱和度在环中适当位置，其中R?3和R4或R'4¿中的一个为可选取代的C¿3-20?杂芳基或C5-20芳基，而另一个为H，或者R?3和R4或R'4¿一起是-A-B-，它们共同代表一个融合的可选取代芳香环。这些化合物还比PI 3-激酶和/或ATM选择性地抑制DNA-PK活性。
• Dna-pk inhibitors
  申请人：——

  公开号：US20040192687A1

  公开（公告）日：2004-09-30

  The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein R 1 and R 2 are independently hydrogen, an optionally substituted C 1-7 alkyl group, C 3-20 heterocyclyl group, or C 5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; X and Y are selected from CR 4 and O, O and CR′ 4 and NR″ 4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R 3 and R 4 or R′ 4 is an optionally substituted C 3-20 heteroaryl or C 5-20 aryl group, and the other of R 3 and R 4 or R′ 4 is H, or R 3 and R 4 or R″ 4 together are —A—B—, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM. 1

  本发明涉及使用式(I)化合物及其异构体、盐、溶剂合物、化学保护形式及其前药，在制备抑制DNA-PK活性的药物方面使用。其中，R1和R2分别为氢、可选取代的C1-7烷基、C3-20杂环基或C5-20芳基，或者与它们连接的氮原子一起形成含有4到8个环原子的可选取代杂环环；X和Y从CR4和O、O和CR'4以及NR"4和N中选择，其中不饱和度在环中适当位置，且R3和R4或R'4中的一个为可选取代的C3-20杂芳基或C5-20芳基，而另一个为氢，或者R3和R4或R"4一起为-A-B-，它们共同表示一个融合的可选取代芳香环。这些化合物与PI 3-激酶和/或ATM相比，也具有选择性抑制DNA-PK活性的作用。
• DNA-PK INHIBITORS
  申请人：Martin Morrison Barr Niall

  公开号：US20070238729A1

  公开（公告）日：2007-10-11

  The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein R 1 and R 2 are independently hydrogen, an optionally substituted C 1-7 alkyl group, C 3-20 heterocyclyl group, or C 5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; X and Y are selected from CR 4 and O, O and CR′ 4 and NR″ 4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R 3 and R 4 or R′ 4 is an optionally substituted C 3-20 heteroaryl or C 5-20 aryl group, and the other of R 3 and R 4 or R′ 4 is H, or R 3 and R 4 or R″ 4 together are -A-B—, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM.

  本发明涉及使用式(I)的化合物及其异构体、盐、溶剂合物、化学保护形式和前药，在制备抑制DNA-PK活性的药物方面有用。其中，R1和R2独立地表示氢、可选取代的C1-7烷基、C3-20杂环基或C5-20芳基，或者与它们连接的氮原子一起形成可选取代的含有4到8个环原子的杂环环；X和Y选自CR4和O，O和CR'4以及NR"4和N，其中不饱和度在环中适当位置，其中R3和R4或R'4中的一个为可选取代的C3-20杂芳基或C5-20芳基，而另一个为H，或者R3和R4或R"4在一起为-A-B-，代表一种融合的可选取代芳香环。这些化合物与PI 3-激酶和/或ATM相比，具有选择性地抑制DNA-PK的活性。