(2E)-N-hydroxy-5-{3-[(phenylamino)sulfonyl]phenyl}pent-2-en-4-ynamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2E)-N-hydroxy-5-{3-[(phenylamino)sulfonyl]phenyl}pent-2-en-4-ynamide
• 英文别名: PX116238；(E)-5-(3-Phenylsulfamoylphenyl)pent-2-en-4-ynoic acid hydroxyamide；(E)-N-hydroxy-5-[3-(phenylsulfamoyl)phenyl]pent-2-en-4-ynamide
• 化学式: C₁₇H₁₄N₂O₄S
• 分子量: 342.375
• InChiKey: FPOPEGHAIAVNDU-LFYBBSHMSA-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：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 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：

  3-溴苯磺酰氯 在 四(三苯基膦)钯 sodium hydroxide 、 copper(l) iodide 、 草酰氯 、 sodium hydride 、 sodium carbonate 、 戴斯-马丁氧化剂 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙腈 、 苯 为溶剂， 反应 4.17h， 生成 (2E)-N-hydroxy-5-{3-[(phenylamino)sulfonyl]phenyl}pent-2-en-4-ynamide
  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：——

  公开号：US20040077726A1

  公开（公告）日：2004-04-22

  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; Q1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S (═O)2NR1— and —NR1S(═O)2—; R1 is a sulfonamido substituent; and, Q2 is an acid leader group; with the proviso that if J is —S(═O)2NR1—, then Q1 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.

  这项发明涉及抑制HDAC活性的某些活性碳酸酯化合物，其化学式如下：(I) A为芳基；Q1为共价键或芳基引导基团；J为从以下选取的磺胺酰胺连接：—S(═O)2NR1—和—NR1S(═O)2—；R1为磺胺基取代基；Q2为酸引导基团；但条件是如果J为—S(═O)2NR1—，则Q1为芳基引导基团；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药物组合物，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。
• [EN] CARBAMIC ACID COMPOUNDS COMPRISING A SULFONAMIDE LINKAGE AS HDAC INHIBITORS<br/>[FR] COMPOSES D'ACIDE CARBAMIQUE COMPRENANT UNE LIAISON SULFONAMIDE EN TANT QU'INHIBITEURS DE HDAC
  申请人：PROLIFIX LTD

  公开号：WO2002030879A2

  公开（公告）日：2002-04-18

  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; Q1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: -S(=O)¿2NR?1- and -NR1S(=O)2-; R1 is a sulfonamido substituent; and, Q2 is an acid leader group; with the proviso that if J is -S(=O)¿2NR?1-, then Q1 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类化合物，其抑制HDAC活性，并具有以下式子：（I）其中，A是芳基基团；Q1是共价键或芳基领导基团；J是从-S（=O）2NR1-和-NR1S（=O）2-中选择的磺酰胺键；R1是磺酰胺基取代基；Q2是酸领导基团；前提是如果J是-S（=O）2NR1-，则Q1是芳基领导基团；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。本发明还涉及包含此类化合物的药物组合物以及使用这些化合物和组合物，无论是体外还是体内，来抑制HDAC，例如抑制增殖性疾病，如癌症和牛皮癣。
• Carbamic acid compounds comprising a sulfonamide linkage as HDAC inhibitors
  申请人：Watkins J. Clare

  公开号：US20050085515A1

  公开（公告）日：2005-04-21

  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的碳酰胺酸化合物，其抑制HDAC活性，其化学式为：（I）其中，A是芳基基团；Q1是共价键或芳基领导基团；J是从以下选择的磺酰胺键链：—S（═O）2NR1—和—NR1S（═O）2—；R1是磺酰胺取代基；Q2是酸领导基团；但是，如果J是—S（═O）2NR1—，则Q1是芳基领导基团；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，以及使用这种化合物和组合物，在体内外抑制HDAC，例如抑制增生状况，如癌症和牛皮癣。
• 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。
• US6888027B2
  申请人：——

  公开号：US6888027B2

  公开（公告）日：2005-05-03