5-(2,4-bis(benzyloxy)-5-chlorophenyl)-4-bromoisoxazole-3-carboxylic acid ethylamide | 747413-06-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(2,4-bis(benzyloxy)-5-chlorophenyl)-4-bromoisoxazole-3-carboxylic acid ethylamide
• 英文别名: 5-(2,4-bis-benzyloxy-5-chlorophenyl)-4-bromo-isoxazole-3-carboxylic acid ethylamide；5-(2,4-Bis(benzyloxy)-5-chlorophenyl)-4-bromo-N-ethyl-isoxazole-3-carboxamide；5-(2,4-Bis(benzyloxy)-5-chlorophenyl)-4-bromo-N-ethylisoxazole-3-carboxamide；4-bromo-5-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-N-ethyl-1,2-oxazole-3-carboxamide
• CAS: 747413-06-5
• 化学式: C₂₆H₂₂BrClN₂O₄
• 分子量: 541.829
• InChiKey: FAQQNPUMRKZXOQ-UHFFFAOYSA-N

物化性质

• 沸点：
  646.8±55.0 °C(Predicted)
• 密度：
  1.406±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(2,4-bis(benzyloxy)-5-chlorophenyl)-4-bromoisoxazole-3-carboxylic acid ethylamide 、 4-(叔丁基二甲基硅氧基)苯基硼酸 在 bis-triphenylphosphine-palladium(II) chloride 碳酸氢钠 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到5-(2,4-Bis(benzyloxy)-5-chlorophenyl)-N-ethyl-4-(4-hydroxy-phenyl)-isoxazole-3-carboxamide
  参考文献：
  名称：

  HSP90 INHIBITORS CONTAINING A ZINC BINDING MOIETY

  摘要：

  本发明涉及含有锌结合基团的HSP90抑制剂及其在治疗细胞增殖性疾病如癌症中的应用。所述衍生物还可能作为HDAC抑制剂。

  公开号：

  US20090076006A1
• 作为产物：
  描述：

  5-(2,4-bis(benzyloxy)-5-chlorophenyl)isoxazole-3-carboxylic acid ethylamide 在 溴 、 potassium acetate 、 溶剂黄146 作用下， 反应 0.08h， 以85.4%的产率得到5-(2,4-bis(benzyloxy)-5-chlorophenyl)-4-bromoisoxazole-3-carboxylic acid ethylamide
  参考文献：
  名称：

  HSP90 INHIBITORS CONTAINING A ZINC BINDING MOIETY

  摘要：

  本发明涉及含有锌结合基团的HSP90抑制剂及其在治疗细胞增殖性疾病如癌症中的应用。所述衍生物还可能作为HDAC抑制剂。

  公开号：

  US20090076006A1

文献信息

• [EN] ISOXAZOLE COMPOUNDS AS INHIBITORS OF HEAT SHOCK PROTEINS<br/>[FR] COMPOSES D'ISOXAZOLE UTILES COMME INHIBITEURS DES PROTEINES DE CHOC THERMIQUE
  申请人：VERNALIS CAMBRIDGE LTD

  公开号：WO2004072051A1

  公开（公告）日：2004-08-26

  Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: (A), (B) wherein R1, is a group of formula (IA): -Ar1-(Alk1)p-(Z)r-(Alk2)S-Q, wherein in any compatible combination Ar1 is an optionally substituted aryl or heteroaryl radical, Alk1and Alk2 are optionally substituted divalent Cl-C6 alkylene or C2-C6 alkenylene radicals, p, r and s are independently 0 or 1, Z is -0-, -S-, -(C=O)-, -(C=S)-, -SO2-, -C(=O)O-, -C(=O)NRA-, -C(=S)NRA-, - SO2NRA-, -NRAC(=O)-, -NRASO2- or -NRA- wherein RA is hydrogen or Cl-C6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R2 is (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk1)p-(Z)r-(Alk2)s-Q wherein Q, Alk1, Alk2, Z, p, r and s are as defined above in relation to group (IA); and R3 is hydrogen, optionally substituted cycloalkyl, cycloalkenyl, C1-C6 alkyl, C1-C6 alkenyl, or C1-C6 alkynyl; or a carboxyl, carboxamide, or carboxyl ester group.

  式(A)或(B)的异唑唑烷是HSP90活性的抑制剂，可用于治疗癌症等疾病：其中R1是式(IA)的一个基团：-Ar1-(Alk1)p-(Z)r-(Alk2)S-Q，其中在任何兼容的组合中，Ar1是可选择地取代的芳基或杂环基团，Alk1和Alk2是可选择地取代的二价Cl-C6烷基或C2-C6烯基基团，p、r和s独立地为0或1，Z是-0-，-S-，-(C=O)-，-(C=S)-，-SO2-，-C(=O)O-，-C(=O)NRA-，-C(=S)NRA-，-SO2NRA-，-NRAC(=O)-，-NRASO2-或-NRA-，其中RA是氢或Cl-C6烷基，Q是氢或一个可选择地取代的脂环或杂环基团；R2是(i)上述式(IA)的一个基团或(ii)一个羧酰胺基团；或(iii)一个非芳香的脂环或杂环环，其中一个环碳原子可选择地取代，和/或一个环氮原子可选择地被一个式-(Alk1)p-(Z)r-(Alk2)s-Q的基团取代，其中Q、Alk1、Alk2、Z、p、r和s如上所述与式(IA)相关的基团定义；R3是氢，可选择地取代的环烷基、环烯烃基、C1-C6烷基、C1-C6烯基或C1-C6炔基；或一个羧基、羧酰胺基或羧酸酯基团。
• Isoxazole compounds as inhibitors of heat shock proteins
  申请人：Drysdale James Martin

  公开号：US20060241106A1

  公开（公告）日：2006-10-26

  Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: (A), (B) wherein R 1 , is a group of formula (IA): —Ar 1 -(Alk 1 )p-(Z) r -(Alk 2 ) s -Q, wherein in any compatible combination Ar 1 is an optionally substituted aryl or heteroaryl radical, Alk 1 and Alk 2 are optionally substituted divalent C 1 -C 6 alkylene or C 2 -C 6 alkenylene radicals, p, r and s are independently 0 or 1, Z is -0-, —S—, —(C═O)—, —(C═S)—, —SO 2 —, —C(═O)O—, —C(═O)NR A —, —C(═S)NR A —, —SO 2 NR A —, —NR A C(═O)—, —NR A SO 2 — or —NR A — wherein R A is hydrogen or C 1 -C 6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R 2 is (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk 1 )p-(Z) r -(Alk 2 ) s -Q wherein Q, Alk 1 , Alk 2 , Z, p, r and s are as defined above in relation to group (IA); and R 3 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.

  式(A)或(B)的异噁唑是HSP90活性的抑制剂，可用于治疗癌症等疾病：(A)、(B)其中R1是以下式子的基团：-Ar1-(Alk1)p-(Z)r-(Alk2)s-Q，其中在任何兼容的组合中，Ar1是可选取代的芳基或杂环基团，Alk1和Alk2是可选取代的二价C1-C6烷基或C2-C6烯基基团，p、r和s是独立的0或1，Z是-0-、-S-、-(C═O)-、-(C═S)-、-SO2-、-C(═O)O-、-C(═O)NRA-、-C(═S)NRA-、-SO2NRA-、-NRAC(═O)-、-NRASO2-或-NRA-，其中RA是氢或C1-C6烷基，Q是氢或可选取代的碳环或杂环基团；R2是(i)上述式(Ia)的基团，或(ii)羧酰胺基团，或(iii)非芳香碳环或杂环环，其中一个环碳原子可选取代，和/或一个环氮原子可选取代为以下式子的基团：-(Alk1)p-(Z)r-(Alk2)s-Q，其中Q、Alk1、Alk2、Z、p、r和s如上所述；R3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；或羧基、羧酰胺基或羧酸酯基团。
• Multi-Functional Small Molecules as Anti-Proliferative Agents
  申请人：Cai Xiong

  公开号：US20080221132A1

  公开（公告）日：2008-09-11

  The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.

  本发明涉及一种新型选择性抑制多种细胞或分子靶点的组合物、方法和应用。更具体地说，本发明涉及多功能小分子，其中一种功能能够抑制组蛋白去乙酰化酶（HDAC），另一种功能能够抑制与异常细胞增殖、分化或存活有关的不同细胞或分子途径。
• Isoxazole Compounds As Inhibitors Of Heat Shock Proteins
  申请人：Drysdale Martin James

  公开号：US20120252797A1

  公开（公告）日：2012-10-04

  Isoxazoles of formula (A) or (B) wherein R 1 is a group of formula (IB) The isoxazoles are inhibitors of HSP90 activity, and useful for the treatment of, for example, cancers.

  化合物的式子为(A)或(B)，其中R1为式子(IB)所代表的基团。这些异噁唑是HSP90活性的抑制剂，可用于治疗癌症等疾病。
• Isozazole Compounds As Inhibitors Of Heat Shock Proteins
  申请人：Drysdale Martin James

  公开号：US20100179138A1

  公开（公告）日：2010-07-15

  Isoxazoles of formula (A) or (B) are inhibitors of HSP90 activity, and useful for treatment of, for example cancers: wherein R 1 , is a group of formula (IA): —Ar 1 -(Alk 1 ) p -(Z) r -(Alk 2 ) s -Q, wherein in any compatible combination Ar 1 is an optionally substituted aryl or heteroaryl radical, Alk 1 and Alk 2 are optionally substituted divalent C 1 -C 6 alkylene or C 2 -C 6 alkenylene radicals, p, r and s are independently 0 or 1, Z is -0-, —S—, —(C═O)—, —(C═S)—, —SO.sub.2-, —C(═O)O—, —C(═O)NR A —, —C(═S)NR A —, —SO 2 NR A —, —NR A C(═O)—, —NR A SO 2 —or —NR A — wherein R A is hydrogen or C 1 -C 6 alkyl, and Q is hydrogen or an optionally substituted carbocyclic or heterocyclic radical; R 2 is (i) a group of formula (IA) above or (ii) a carboxamide radical; or (iii) a non aromatic carbocyclic or heterocyclic ring wherein a ring carbon is optionally substituted, and/or a ring nitrogen is optionally substituted by a group of formula -(Alk 1 ) p -(Z) r -(Alk 2 ) s -Q wherein Q, Alk 1 , Alk 2 , Z, p, r and s are as defined above in relation to group (IA); and R 3 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.

  式（A）或（B）的异噁唑是HSP90活性的抑制剂，可用于治疗癌症，例如：其中R1是以下式（IA）的基团：—Ar1-(Alk1)p-(Z)r-(Alk2)s-Q，其中在任何兼容的组合中，Ar1是可选取代的芳基或杂环芳基基团，Alk1和Alk2是可选取代的二价C1-C6烷基或C2-C6烯基基团，p，r和s独立地为0或1，Z为-0-，—S—，—（C═O）—，—（C═S）—，—SO.sub.2-，—C（═O）O—，—C（═O）NRA—，—C（═S）NRA—，—SO2NRA—，—NRAC（═O）—，—NRASO2—或—NRA—，其中RA为氢或C1-C6烷基，并且Q为氢或可选取代的碳环或杂环基团；R2为（i）上述式（IA）的基团或（ii）一个羧酰胺基团；或（iii）一个非芳香碳环或杂环环，其中一个环碳原子可选取代，和/或一个环氮原子可选取代为以下式的基团-(Alk1)p-(Z)r-(Alk2)s-Q，其中Q，Alk1，Alk2，Z，p，r和s如上所述定义于基团（IA）；和R3为氢，可选取代的环烷基，环烯基，C1-C6烷基，C1-C6烯基或C1-C6炔基；或羧基，羧酰胺基或羧酸酯基。