N-(6-(hydroxyamino)-6-oxohexyl)-2-naphthamide | 408356-88-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-(6-(hydroxyamino)-6-oxohexyl)-2-naphthamide
• 英文别名: Naphthalene-2-carboxylic acid (5-hydroxycarbamoylpentyl)amide；N-[6-(hydroxyamino)-6-oxohexyl]naphthalene-2-carboxamide
• CAS: 408356-88-7
• 化学式: C₁₇H₂₀N₂O₃
• 分子量: 300.357
• InChiKey: DQWSLVMETKWWJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  78.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-[(2-naphthylcarbonyl)amino]hexanoic acid 在 N-乙基吗啉 、 O‐(1H‐benzotriazol‐1‐yl)‐N,N,N′,N′‐tetramethyluronium tetrafluoroborate 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 、 二氯甲烷 为溶剂， 反应 6.0h， 以55%的产率得到N-(6-(hydroxyamino)-6-oxohexyl)-2-naphthamide
  参考文献：
  名称：

  从固相支持物中光解释放异羟肟酸和羧酰胺的溶剂控制化学选择性

  摘要：

  提出了光不稳定性羟胺连接剂的合成用途和理论基础。所开发的方案使得能够从固体支持物上高效合成和化学选择性光解释放异羟肟酸酯或羧酰胺。接头单元的双分离模式唯一取决于溶剂。异羟肟酸是通过在质子传递溶剂中进行光解而获得的，而在非质子传递溶剂中的光解能够选择性释放羧酰胺。

  DOI：

  10.1021/acs.orglett.7b01386

文献信息

• Carbamic acid compounds comprising an amide linkage as hdac inhibitors
  申请人：——

  公开号：US20040092598A1

  公开（公告）日：2004-05-13

  This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the formula (1) wherein: A is an aryl group; Q1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: —NR1C(═O)—and —C(═O)NR1—; R1 is an amido substituent; and, Q2 is an acid 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酰胺化合物，其化学式为（1），其中：A是芳基；Q1是至少有2个碳原子骨架的芳基前导基团；J是选择自以下的酰胺键：—NR1C(═O)—和—C(═O)NR1—；R1是酰胺取代基；Q2是酸前导基团；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，以及在体外和体内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。
• Carbamic acid compounds comprising an amide linkage as HDAC inhibitors
  申请人：Topotarget UK Limited

  公开号：US07880020B2

  公开（公告）日：2011-02-01

  This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the formula (1) wherein: A is an aryl group; Q1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: —NR1C(═O)— and —C(═O)NR1—; R1 is an amido substituent; and, Q2 is an acid 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 psorias.

  本发明涉及一些活性碳酰胺酸化合物，其抑制HDAC活性，其公式（1）如下：其中：A是芳基基团；Q1是具有至少2个碳原子骨架的芳基导向基团；J是选择自：—NR1C（═O）—和—C（═O）NR1—的酰胺键；R1是酰胺取代基；而Q2是酸导向基团；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，无论是体外还是体内，来抑制HDAC，例如，抑制增殖性疾病，如癌症和银屑病。
• CARBAMIC ACID COMPOUNDS COMPRISING AN AMIDE LINKAGE AS HDAC INHIBITORS
  申请人：Watkins Clare J.

  公开号：US20110105572A1

  公开（公告）日：2011-05-05

  This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: wherein: A is a C 5-20 heteroaryl or C 5-20 carboaryl group and is optionally substituted; Q 1 is a C 2-7 alkylene group having a backbone of at least 2 carbon atoms, and is optionally substituted; J is —N(R 1 )C(═O)— or —C(═O)N(R 1 )—; R 1 is hydrogen, C 1-7 alkyl, C 3-20 heterocyclyl, or C 5-20 aryl; and, Q 2 is C 1-7 alkylene, C 5-20 arylene, C 5-20 arylene-C 1-7 alkylene, or C 1-7 alkylene-C 5-20 arylene having a backbone of at least 3 carbon atoms, and is optionally substituted; and pharmaceutically acceptable salts 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 treat 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，并具有以下公式：其中：A是C5-20杂环芳基或C5-20羰基芳基基团，并可选择性地取代；Q1是具有至少2个碳原子的C2-7烷基链，可选择性地取代；J是-N（R1）C（═O）-或-C（═O）N（R1）-；R1是氢，C1-7烷基，C3-20杂环芳基或C5-20芳基；Q2是具有至少3个碳原子的C1-7烷基链，C5-20芳基链，C5-20芳基链-C1-7烷基链，或C1-7烷基链-C5-20芳基链，并可选择性地取代；以及其药学上可接受的盐。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，例如治疗增殖性疾病，如癌症和牛皮癣。
• Pde4 inhibitors for the treatment of neoplasms of lymphoid cells
  申请人：Braunger Jurgen

  公开号：US20060148804A1

  公开（公告）日：2006-07-06

  The invention relates to the use of certain PDE4 inhibitors alone or in combination with one or more differentiation inducing agents and/or an agent effective in raising intracellular concentrations of cAMP or a stable analogue of cAMP in the preparation of pharmaceutical compositions for the treatment of neoplasms of lymphoid cells.

  本发明涉及某些 PDE4 抑制剂单独或与一种或多种分化诱导剂和/或一种能有效提高细胞内 cAMP 或稳定的 cAMP 类似物浓度的药剂联合使用，制备治疗淋巴细胞肿瘤的药物组合物。
• Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR
  作者：Victor Andrianov、Vija Gailite、Daina Lola、Einars Loza、Valentina Semenikhina、Ivars Kalvinsh、Paul Finn、Kamille Dumong Petersen、James W.A. Ritchie、Nagma Khan

  DOI：10.1016/j.ejmech.2008.06.020

  日期：2009.3

  Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent HDAC inhibitors (HDACi), with IC50 values in the low nanomolar (W) range against enzyme activity in HeLa cell extracts and sub-mu M for their in vitro anti-proliferative effect on cell lines. The introduction of an unsaturated linking group between the terminal aryl ring and the amide moiety was the key to obtain good potency. This approach yielded compounds such as (E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(7-quinolinyl)-2-propenamide (27) (HDAC IC50 8 nM) which showed potent in vivo activity in the P388 mouse leukemia syngeneic model (an increased lifespan (ILS) of 111% was obtained). (C) 2008 Elsevier Masson SAS. All rights reserved.