3-(2,4-bis-benzyloxy-5-chlorophenyl)-4-bromo-1H-pyrazole | 705963-56-0

• 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)-4-bromo-1H-pyrazole
• 英文别名: 3-(2,4-bis-benzyloxy-5-chloro-phenyl)-4-bromo-1H-pyrazole；4-bromo-5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-1H-pyrazole
• CAS: 705963-56-0
• 化学式: C₂₃H₁₈BrClN₂O₂
• 分子量: 469.765
• InChiKey: YFYLUMBIVFLEKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  29
• 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)-4-bromo-1H-pyrazole 、 磺胺米隆 、 二氧化碳 生成 N-[4-(Aminosulfonyl)benzyl]-5-(5-chloro-2,4-dihydroxyphenyl)-1H-pyrazole-4-carboxamide
  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
• 作为产物：
  描述：

  4-氯间苯二酚 在 N-溴代丁二酰亚胺(NBS) 、 三氟化硼乙醚 、 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 21.75h， 生成 3-(2,4-bis-benzyloxy-5-chlorophenyl)-4-bromo-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-(2-HYDROXY-PHENYL)-1H-PYRAZOLE-4-CARBOXYLIC ACID AMIDE DERIVATIVES AS HSP90 INHIBITORS FOR THE TREATMENT OF CANCER<br/>[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
  申请人：VERNALIS CAMBRIDGE LTD

  公开号：WO2004050087A1

  公开（公告）日：2004-06-17

  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; 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。
• 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-(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：EP1567151B1

  公开（公告）日：2006-03-15
• RUBBER COMPOSITION
  申请人：NOHARA Daisuke

  公开号：US20100298488A1

  公开（公告）日：2010-11-25

  Provided is a rubber composition comprising an inorganic filler, a compound having at least one group A reacting with a rubber and two or more groups B adsorbing on the inorganic filler described above in the same molecule, a compound having the group A reacting with a rubber and an amino group in the same molecule or acrylate or methacrylate having a specific structure and further comprising, if necessary, a silane coupling agent. This makes it possible to provide a rubber composition which is excellent in the dispersibility of an inorganic filler, so that it does not elevate a viscosity of a non-vulcanized rubber and does not damage the processability and which does not bring about roughening on the surface of a rubber and is improved in a storage modulus.