3-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxylic acid | 558640-40-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxylic acid
• 英文别名: 5-(5-chloro-2,4-dihydroxy-phenyl)-4-(4-methoxy-phenyl)-2H-pyrazole-3-carboxylic acid；3-(5-Chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxylic acid
• CAS: 558640-40-7
• 化学式: C₁₇H₁₃ClN₂O₅
• 分子量: 360.754
• InChiKey: VIBPEGKTQCWOSK-UHFFFAOYSA-N

物化性质

• 沸点：
  612.3±55.0 °C(Predicted)
• 密度：
  1.522±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxylic acid 在 N-甲基吗啉 氨 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 3-(5-Chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxamide
  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：

  6-chloro-7-hydroxy-3-(4-methoxyphenyl)-4-oxo-4H-chromene-2-carboxylic acid 在 碳酸氢钠 、 肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 3-(5-chloro-2,4-dihydroxyphenyl)-4-(4-methoxyphenyl)-1H-pyrazole-5-carboxylic acid
  参考文献：
  名称：

  [EN] PYRAZOLE COMPOUNDS AS HSP90 INHIBITORS FOR THE TREATMENT OF CANCER
  [FR] COMPOSES DE PYRAZOLE SERVANT D'INHIBITEURS DE HSP90 DANS LE TRAITEMENT DU CANCER

  摘要：

  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。

  公开号：

  WO2004096212A1

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。
• Pyrazole compounds as HSP90 inhibitors for the treatment of cancer
  申请人：Vernalis (Cambridge) Limited

  公开号：US07632855B2

  公开（公告）日：2009-12-15

  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活性抑制剂，可用于治疗增殖性疾病，如癌症：其中R1，R2和R3如规范中所定义，X是-OR4或-NR4R5，其中R4和R5独立地代表氢或可选地取代的C1-C6烷基，或者R4和R5与它们所连接的氮一起形成具有5-8个环原子的可选取代含氮环。