(E)-N-hydroxy-3-{3-{[(2-phenylethyl)amino]sulfonyl}phenyl}-N-hydroxyprop-2-enamide | 866323-49-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-N-hydroxy-3-{3-{[(2-phenylethyl)amino]sulfonyl}phenyl}-N-hydroxyprop-2-enamide
• 英文别名: PX106512；N-Hydroxy-3-(3-(phenethylsulfamoyl)phenyl)acrylamide；(E)-N-hydroxy-3-[3-(2-phenylethylsulfamoyl)phenyl]prop-2-enamide
• CAS: 866323-49-1
• 化学式: C₁₇H₁₈N₂O₄S
• 分子量: 346.407
• InChiKey: LYXZDMJNNHSGSR-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (E)-3-(3-甲氧基-3-氧代-1-丙烯-1-基)苯磺酸钠 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 5.0h， 生成 (E)-N-hydroxy-3-{3-{[(2-phenylethyl)amino]sulfonyl}phenyl}-N-hydroxyprop-2-enamide
  参考文献：
  名称：

  新型磺酰胺衍生物作为组蛋白脱乙酰基酶的抑制剂

  摘要：

  抑制酶组蛋白脱乙酰基酶（HDAC）成为一种新型的癌症治疗方法。合成了一系列新颖的磺酰胺衍生物，并对其抑制人HDAC的能力进行了评估。鉴定出有效酶抑制剂的化合物，IC 50相对于从HeLa细胞提取物中获得的酶而言，其在低纳摩尔浓度范围内的值较低，并且对细胞培养具有抗增殖作用。该系列的结构-活动关系的广泛表征确定了活动的关键要求。这些包括磺酰胺键的方向和中心苯环上的取代模式。芳族头基和磺酰胺官能团之间的烷基间隔基也影响了HDAC的抑制活性。其中一种化合物m 11.1（也称为PXD101）已进入实体瘤和血液系统恶性肿瘤的临床试验。

  DOI：

  10.1002/hlca.200590129

文献信息

• Carbamic acid compounds comprising a sulfonamide linkage as HDAC inhibitors
  申请人：Kalvinsh Ivars

  公开号：US20070004806A1

  公开（公告）日：2007-01-04

  This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q 1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S(═O) 2 NR 1 — and —NR 1 S(═O) 2 —; R 1 is a sulfonamido substituent; and, Q 2 is an acid leader group; with the proviso that if J is —S(═O) 2 NR 1 —, then Q 1 is an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

  本发明涉及抑制HDAC活性的某些活性碳酸酰化合物，其具有以下式子：（I）其中A是芳基；Q1是共价键或芳基引导基团；J是选自磺酰胺连接的以下链：—S（═O）2NR1—和—NR1S（═O）2—；R1是磺酰胺取代基；Q2是酸引导基团；但是，如果J是—S（═O）2NR1—，则Q1是芳基引导基团；以及其药学上可接受的盐，溶剂化物，酰胺，酯，醚，化学保护形式和前药。本发明还涉及包含这种化合物的制药组合物，以及在体内外使用这种化合物和组合物抑制HDAC，例如抑制增殖性疾病，如癌症和银屑病。
• CARBAMIC ACID COMPOUNDS COMPRISING A SULFONAMIDE LINKAGE AS HDAC INHIBITORS
  申请人：Watkins Clare J.

  公开号：US20080161401A1

  公开（公告）日：2008-07-03

  This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q 1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S(═O) 2 NR 1 — and —NR 1 S(═O) 2 —; R 1 is a sulfonamido substituent; and, Q 2 is an acid leader group; with the proviso that if J is —S(═O) 2 NR 1 —, then Q 1 is an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

  本发明涉及某些活性碳酰胺酸化合物，其抑制HDAC活性，具有以下公式：（I）其中，A是芳基基团；Q1是共价键或芳基引导基团；J是从以下选择的磺酰胺键连接：—S（═O）2NR1—和—NR1S（═O）2—；R1是磺酰胺取代基；Q2是酸引导基团；但是，如果J是—S（═O）2NR1—，则Q1是芳基引导基团；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。本发明还涉及包含这种化合物的制药组合物，以及在体内外使用这种化合物和组合物来抑制HDAC，例如，抑制增殖性疾病，如癌症和牛皮癣。
• Pharmaceutical formulations of HDAC inhibitors
  申请人：TopoTarget UK Limited

  公开号：EP2494969A1

  公开（公告）日：2012-09-05

  This invention pertains to pharmaceutical compositions comprising certain carbamic acid compounds (e.g., which inhibit HDAC (histone deacetylase) activity) (e.g., PXD-101, N-hydroxy-3-(3-phenylsulfamoyl-phenyl)-acrylamide)) and one or more additional ingredients selected from cyclodextrin, arginine, and meglumine. The present invention also pertains to the use of such compositions, for example, in the inhibition of HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

  本发明涉及包含某些氨基甲酸化合物（例如抑制 HDAC（组蛋白去乙酰化酶）活性的化合物）（例如 PXD-101、N-羟基-3-(3-苯基氨基磺酰基苯基)-丙烯酰胺）和一种或多种选自环糊精、精氨酸和巨鲁明的附加成分的药物组合物。本发明还涉及此类组合物的用途，例如用于抑制 HDAC 以及治疗 HDAC 介导的疾病、癌症、增殖性疾病、牛皮癣等。
• Imaging histone deacetylases with a radiotracer using positron emission tomography
  申请人：THE GENERAL HOSPITAL CORPORATION

  公开号：US10188756B2

  公开（公告）日：2019-01-29

  Disclosed herein are histone deacetylase imaging agents for positron emission tomography and related imaging methods using the histone deacetylase imaging agents. The histone deacetylase imaging agents may be a compound of formula (I): wherein R1 is a moiety including a positron emitter; R2 represents hydrogen, or substituted or unsubstituted alkyl, or substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and n is an integer selected from 0 or 1. In one version of the compound of formula (I), R1 is a moiety including an adamantyl group.

  本文公开了用于正电子发射断层扫描的组蛋白去乙酰化酶成像剂和使用组蛋白去乙酰化酶成像剂的相关成像方法。组蛋白去乙酰化酶成像剂可以是式 (I) 的化合物：其中 R1 是包括正电子发射体的分子；R2 代表氢，或取代或未取代的烷基，或取代或未取代的芳基，或取代或未取代的杂芳基；n 是选自 0 或 1 的整数。在一种式（I）化合物中，R1 是包括金刚烷基的分子。
• Combination therapies using HDAC inhibitors
  申请人：TopoTarget UK Limited

  公开号：US10285959B2

  公开（公告）日：2019-05-14

  The present invention pertains to a method for treating cancer, such as lung cancer, multiple myeloma, lymphoma, and epithelial ovarian cancer, comprising the administration to a patient in need thereof a first amount or dose of a histone deacetylase (HDAC) inhibitor, such as PXD-101, and a second amount or dose of another chemotherapeutic agent, such as dexamethasone or 5-fluorouracil, or an epidermal growth factor receptor (EGFR) inhibitor, such as TarcevaÚ, wherein the first and second amounts or doses together comprise a therapeutically effective amount.

  本发明涉及一种治疗癌症（如肺癌、多发性骨髓瘤、淋巴瘤和上皮性卵巢癌）的方法，包括向有需要的患者施用第一种量或剂量的组蛋白去乙酰化酶（HDAC）抑制剂，如 PXD-101，以及第二种量或剂量的另一种化疗药物，如地塞米松或 5-氟尿嘧啶，或表皮生长因子受体（EGFR）抑制剂，如 PXD-101、和第二种量或剂量的另一种化疗药物，如地塞米松或 5-氟尿嘧啶，或表皮生长因子受体（EGFR）抑制剂，如 TarcevaÚ，其中第一和第二种量或剂量共同构成治疗有效量。