1-(5-chloro-2,4-dihydroxyphenyl)-2-(4-methoxyphenyl)ethanone | 558643-16-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-(5-chloro-2,4-dihydroxyphenyl)-2-(4-methoxyphenyl)ethanone
• 英文别名: 5-chloro-2,4-dihydroxyphenyl-4-methoxybenzylketone；1-(5-chloro-2,4-dihydroxy-phenyl)-2-(4-methoxy-phenyl)-ethanone
• CAS: 558643-16-6
• 化学式: C₁₅H₁₃ClO₄
• 分子量: 292.719
• InChiKey: JBCBFFFUINBPCU-UHFFFAOYSA-N

物化性质

• 沸点：
  489.5±24.0 °C(Predicted)
• 密度：
  1.364±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(5-chloro-2,4-dihydroxyphenyl)-2-(4-methoxyphenyl)ethanone 在 吡啶 、 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 9.0h， 生成 6-chloro-7-hydroxy-3-(4-methoxyphenyl)-4-oxo-4H-chromene-2-carboxylic acid
  参考文献：
  名称：

  Novel, Potent Small-Molecule Inhibitors of the Molecular Chaperone Hsp90 Discovered through Structure-Based Design

  摘要：

  The crystal structure of a previously reported screening hit 1 (CCT018159) bound to the N terminal domain of molecular chaperone Hsp90 has been used to design 5-amide analogues. These exhibit enhanced potency against the target in binding and functional assays with accompanying appropriate cellular pharmaeodynamic changes. Compound 11 (VER-49009) compares favorably with the clinically evaluated 17-AAG.

  DOI：

  10.1021/jm050355z
• 作为产物：
  描述：

  对甲氧基苯乙酸 、 4-氯间苯二酚 在 三氟化硼乙醚 作用下， 反应 3.0h， 以86%的产率得到1-(5-chloro-2,4-dihydroxyphenyl)-2-(4-methoxyphenyl)ethanone
  参考文献：
  名称：

  作为潜在的α-葡萄糖苷酶抑制剂的烷氧基异黄酮的合成

  摘要：

  本研究的目的是合成异黄酮-烯胺酮3a-c和 7-烷氧基-异黄酮4a-c，评估它们对 α-葡萄糖苷酶的抑制作用，并分析这些苯并吡喃衍生物中芳香部分存在与否的生物等排效应. 与阳性对照阿卡波糖相比，所有测试化合物都表现出对α-葡糖苷酶的更大抑制。异黄酮3a-c和4a-c系列显示出 比亲本 7-羟基异黄酮2a-c (IC 50 = 109.4-173.2 µM)更高的抑制活性 (IC 50  = 6.3–87.6 µM)，这表明 4 '-氯苯乙酮部分连接到2a的 7-羟基上-c是增加α-葡萄糖苷酶抑制的有效方法。此外，根据对接计算，系列化合物3和4的芳香部分通过疏水效应增强抑制活性。

  DOI：

  10.1007/s00044-022-02910-1

文献信息

• [EN] PYRAZOLE COMPOUNDS AS HSP90 INHIBITORS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSES DE PYRAZOLE SERVANT D'INHIBITEURS DE HSP90 DANS LE TRAITEMENT DU CANCER
  申请人：VERNALIS CAMBRIDGE LTD

  公开号：WO2004096212A1

  公开（公告）日：2004-11-11

  Compounds of formula (I) are inhibitors of HSP90 activity, and useful in the treatment of proliferative disease such as cancers: wherein R1, R2 and R3 are as defined in the specification, and X is -OR4 or - NR4R5 wherein R4 and R5 independently represent hydrogen or optionally substituted C1-C6 alkyl, or R4 and R5 taken together with the nitrogen to which they are attached form an optionally substituted nitrogen-containing ring having 5-8 ring atoms.

  公式（I）的化合物是HSP90活性的抑制剂，并在治疗增生性疾病如癌症中有用：其中R1、R2和R3如规范中定义，X是-OR4或-NR4R5，其中R4和R5独立表示氢或可选择性取代的C1-C6烷基，或R4和R5连同它们连接到的氮原子形成一个具有5-8个环原子的可选择性取代的含氮环。
• [EN] 3,4-DIARYLPYRAZOLES AND THEIR USE IN THE THERAPY OF CANCER<br/>[FR] 3,4-DIARYLPYRAZOLES ET LEUR UTILISATION EN THERAPIE ANTI-CNCEREUSE
  申请人：RIBOTARGETS LTD

  公开号：WO2003055860A1

  公开（公告）日：2003-07-10

  The present invention pertains to the use of certain 3,4-diarylpyrazoles of formula (I), both in vitro and in vivo, to inhibit heat shock protein 90 (HSP90), and in the treatment of conditions mediated by HSP90, including, for example, cancer; wherein: Ar3 is independently: a C5-20aryl group, and is optionally substituted; Ar4 is independently: a C5-20aryl group, and is optionally substituted; R5 is independently: hydrogen; halo; hydroxy; ether; formyl; acyl; carboxy; ester; acyloxy; oxycarbonyloxy; amido; acylamido; aminocarbonyloxy; tetrazolyl; amino; nitro; cyano; azido; sulfhydryl; thioether; sulfonamido; C1-7alkyl; C3-20heterocycyl; or C5-20aryl; RN is independently: -H; C1-7alkyl; C3-20heterocycyl; or, C5-20aryl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, such compounds for medical use, such compounds for use in the treatment of conditions mediated by HSP90, including, for example, cancer, and use of such compounds in the preparation of medicaments for such treatments.

  本发明涉及使用式(I)的特定3,4-二芳基吡唑化合物，无论是体外还是体内，以抑制热休克蛋白90（HSP90）的作用，并用于治疗由HSP90介导的疾病，例如癌症；其中：Ar3独立地表示：C5-20芳基基团，且可选地被取代；Ar4独立地表示：C5-20芳基基团，且可选地被取代；R5独立地表示：氢；卤素；羟基；醚；甲酰基；酰基；羧基；酯基；酰氧基；氧羰基氧基；酰胺基；酰胺氧基；氨基羰氧基；四唑基；氨基；硝基；氰基；偶氮基；硫醇基；硫醚基；磺酰胺基；C1-7烷基；C3-20杂环基；或C5-20芳基；RN独立地表示：-H；C1-7烷基；C3-20杂环基；或C5-20芳基；以及其药学上可接受的盐，溶剂化合物，酰胺，酯，醚，化学保护形式和前药。本发明还涉及这些化合物，包含这些化合物的制药组合物，用于医疗用途的这些化合物，用于治疗由HSP90介导的疾病，例如癌症的这些化合物，以及使用这些化合物制备此类治疗药物的用途。
• 3,4-diarylpyrazoles and their use in the therapy of cancer
  申请人：Drysdale James Martin

  公开号：US20050222230A1

  公开（公告）日：2005-10-06

  The present invention pertains to the use of certain 3,4-diarylpyrazoles of formula (I), both in vitro and in vivo, to inhibit heat shock protein 90 (HSP90), and in the treatment of conditions mediated by HSP90, including, for example, cancer; wherein: Ar 3 is independently: a C 5-20 aryl group, and is optionally substituted; Ar 4 is independently: a C 5-20 aryl group, and is optionally substituted; R 5 is independently: hydrogen; halo; hydroxy; ether; formyl; acyl; carboxy; ester, acyloxy; oxycarbonyloxy; amido; acylamido; aminocarbonyloxy; tetrazolyl; amino; nitro; cyano; azido; sulfhydryl; thioether; sulfonamido; C 1-7 alkyl; C 3-20 heterocycyl; or C 5-20 aryl; RN is independently: —H; C 1-7 alkyl; C 3-20 heterocycyl; or, C 5-20 aryl; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to such compounds, pharmaceutical compositions comprising such compounds, such compounds for medical use, such compounds for use in the treatment of conditions mediated by HSP90, including, for example, cancer, and use of such compounds in the preparation of medicaments for such treatments.

  本发明涉及使用公式（I）中的某些3,4-二芳基吡唑化合物，无论是在体内还是体外，用于抑制热休克蛋白90（HSP90），以及用于治疗由HSP90介导的疾病，包括癌症等；其中：Ar3独立地表示：C5-20芳基基团，可选地取代；Ar4独立地表示：C5-20芳基基团，可选地取代；R5独立地表示：氢；卤素；羟基；醚；甲酰基；酰基；羧基；酯，酰氧基；氧羰酰氧基；酰胺；酰胺基；氨基羰酰氧基；四唑基；氨基；硝基；氰基；偶氮基；磺酰基；硫醚基；磺酰胺基；C1-7烷基；C3-20杂环基；或C5-20芳基；R N 独立地表示：-H；C1-7烷基；C3-20杂环基；或C5-20芳基；以及其药学上可接受的盐，溶剂化合物，酰胺，酯，醚，化学保护形式和前药。本发明还涉及这种化合物，包含这种化合物的制药组合物，用于医学用途的这种化合物，用于治疗由HSP90介导的疾病，包括癌症的这种化合物，以及使用这种化合物制备这种治疗药物的用途。
• Pyrazole compounds as hsp90 inhibitors for the treatment of cancer
  申请人：Barrilalonso Xavier

  公开号：US20070072855A1

  公开（公告）日：2007-03-29

  Compounds of formula (I) are inhibitors of HSP90 activity, and useful in the treatment of proliferative disease such as cancers: wherein R 1 , R 2 and R 3 are as defined in the specification, and X is —OR 4 or —NR 4 R 5 wherein R 4 and R 5 independently represent hydrogen or optionally substituted C 1 -C 6 alkyl, or R 4 and R 5 taken together with the nitrogen to which they are attached form an optionally substituted nitrogen-containing ring having 5-8 ring atoms.

  公式（I）的化合物是HSP90活性抑制剂，可用于治疗增生性疾病，如癌症：其中R1、R2和R3如规范中所定义，X为—OR4或—NR4R5，其中R4和R5独立地表示氢或可选取代的C1-C6烷基，或R4和R5与它们所连接的氮一起形成一个具有5-8个环原子的可选取代的含氮环。
• 5-ARYL-4-(5-SUBSTITUTED 2,4-DIHYDROXYPHENYL)-1,2,3-THIADIAZOLES AS INHIBITORS OF HSP90 CHAPERONE AND THE INTERMEDIATES FOR PRODUCTION THEREOF
  申请人：Matulis Daumantas

  公开号：US20110046387A1

  公开（公告）日：2011-02-24

  Invention is related to novel compounds -5-aryl-4-(5-substituted 2,4-dihydroxyphenyl)-1,2,3-thiadiazoles with general formula (I). The compounds can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit Hsp90 chaperone which participate in cancer progression. This invention is also related to new intermediate compounds which are used for the synthesis of thiadiazoles of general formula (I).

  本发明涉及新化合物-5-芳基-4-(5-取代2,4-二羟基苯基)-1,2,3-噻二唑，其通式为(I)。这些化合物可用于生物医学领域，作为药物制剂中的活性成分，因为它们抑制参与癌症进展的Hsp90伴侣蛋白。本发明还涉及用于合成通式(I)的噻二唑的新中间体化合物。