3-(2,4-bis-benzyloxy-5-chlorophenyl)-1H-pyrazole | 558645-43-5

• 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-(2,4-bis-benzyloxy-5-chlorophenyl)-1H-pyrazole
• 英文别名: 3-(2,4-bis-benzyloxy-5-chloro-phenyl)-1H-pyrazole；5-[2,4-Bis(benzyloxy)-5-chlorophenyl]-1H-pyrazole；5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-1H-pyrazole
• CAS: 558645-43-5
• 化学式: C₂₃H₁₉ClN₂O₂
• 分子量: 390.869
• InChiKey: NYVCGCGZGUXZEJ-UHFFFAOYSA-N

物化性质

• 沸点：
  581.9±50.0 °C(Predicted)
• 密度：
  1.270±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2,4-bis-benzyloxy-5-chlorophenyl)-1H-pyrazole 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以97%的产率得到3-(2,4-bis-benzyloxy-5-chlorophenyl)-4-bromo-1H-pyrazole
  参考文献：
  名称：

  [EN] 3-(2-HYDROXY-PHENYL)-1H-PYRAZOLE-4-CARBOXYLIC ACID AMIDE DERIVATIVES AS HSP90 INHIBITORS FOR THE TREATMENT OF CANCER
  [FR] DERIVES AMIDES D'ACIDE CARBOXYLIQUE 3-(2-HYDROXY-PHENYL)-1H-PYRAZOLE-4 UTILISES EN TANT QU'INHIBITEURS DE HSP90 POUR LE TRAITEMENT DU CANCER

  摘要：

  式（IA）或（IB）的化合物或其盐、N-氧化物、水合物或溶剂化合物是HSP90的抑制剂，并且在癌症的治疗中很有用：式（IA），式（IB）其中Ar是通过环碳连接的芳基或杂环芳基基团，并且在2-位置的碳上被一个羟基取代，否则未取代或可选择性地取代；R1是氢或可选择性取代的C1-C6烷基；R2是氢、可选择性取代的环烷基、环烯烃基、C1-C6烷基、C1-C6烯基或C1-C6炔基；或者是一个羧基、羧酰胺基或羧酯基团；而R3是一个羧酰胺基团。

  公开号：

  WO2004050087A1
• 作为产物：
  描述：

  4-氯间苯二酚 在 三氟化硼乙醚 、 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 19.75h， 生成 3-(2,4-bis-benzyloxy-5-chlorophenyl)-1H-pyrazole
  参考文献：
  名称：

  3-(5-chloro-2,4-dihydroxyphenyl)-Pyrazole-4-carboxamides as inhibitors of the Hsp90 molecular chaperone

  摘要：

  Information from X-ray crystal structures of Hsp90 inhibitors bound to the human Hsp90 molecular chaperone was used to assist in the design of 3-(5-chloro-2,4-dihydroxyphenyl)-pyrazole-4-carboxamides as novel inhibitors of Hsp90. Accessing an extra interaction with the protein via Phe138 gave a significant increase in binding potency compared to similar analogues that do not make this interaction. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.091

文献信息

• [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。
• 3-(2-Hydroxy-phenyl)-1h-pyrazole-4-carboxylic acid amide derivatives as hsp90 inhibitors for the treatment of cancer
  申请人：Beswick Christine Mandy

  公开号：US20070112192A1

  公开（公告）日：2007-05-17

  Compounds of formula (IA) or (IB) or salts, N-oxides. hydrates or solvates thereof are Inhibitors of HSP90, and useful in the treatment of, for example, cancer: formula (IA), formula (IB) wherein Ar is an aryl or heteroaryl radical which is linked via a ring carbon, and which is substituted by a hydroxy group on a carbon in the 2-position, and which is otherwise either unsubstituted or optionally substituted; R 1 is hydrogen or optionally substituted C 1 -C 6 alkyl; R 2 is hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C 1 -C 6 alkyl, C 1 -C 6 alkenyl, or C 1 -C 6 alkynyl; or a carboxyl, carboxamide or carboxyl ester group; and R 3 is a carboxamide group.

  式（IA）或（IB）的化合物或其盐，N-氧化物，水合物或溶剂合物是HSP90的抑制剂，并且在癌症治疗中有用：式（IA），式（IB），其中Ar是通过环碳原子连接的芳基或杂环芳基基团，并且在2位碳上被氢氧基取代，在其他方面要么未取代，要么可选地取代; R1是氢或可选地取代的C1-C6烷基; R2是氢，可选地取代的环烷基，环烯基，C1-C6烷基，C1-C6烯基或C1-C6炔基; 或羧基，羧酰胺或羧酸酯基;和R3是羧酰胺基团。
• 3-(2-hydroxy-phenyl)-1H-pyrazole-4-carboxylic acid amide derivatives as HSP90 inhibitors for the treatment of cancer
  申请人：Vernalis (Cambridge) Limited

  公开号：US07803831B2

  公开（公告）日：2010-09-28

  Compounds of formula (IA) or (IB) or salts, N-oxides, hydrates or solvates thereof are Inhibitors of HSP90, and useful in the treatment of, for example, cancer: formula (IA), formula (IB) wherein Ar is an aryl or heteroaryl radical which is linked via a ring carbon, and which is substituted by a hydroxy group on a carbon in the 2-position, and which is otherwise either unsubstituted or optionally substituted; R1 is hydrogen or optionally substituted C1-C6 alkyl; R2 is hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C1-C6 alkyl, C1-C6alkenyl, or C1-C6 alkynyl; or a carboxyl, carboxamide or carboxyl ester group; and R3 is a carboxamide group.

  式（IA）或（IB）的化合物或其盐，N-氧化物，水合物或溶剂合物是HSP90的抑制剂，可用于治疗癌症等疾病：式（IA），式（IB），其中Ar是通过环碳原子连接的芳基或杂环芳基基团，并且在2位碳上取代了一个羟基，否则未取代或可选取代；R1是氢或可选取代的C1-C6烷基；R2是氢，可选取代的环烷基，环烯基，C1-C6烷基，C1-C6烯基或C1-C6炔基；或者是一个羧基，羧酰胺或羧酸酯基团；R3是一个羧酰胺基团。
• 3,4-DIARYLPYRAZOLES AND THEIR USE IN THE THERAPY OF CANCER
  申请人：Vernalis (Oxford) Ltd

  公开号：EP1456180A1

  公开（公告）日：2004-09-15