8-(hydroxyamino)-8-oxo-N-phenethyloctanamide | 408357-43-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 8-(hydroxyamino)-8-oxo-N-phenethyloctanamide
• 英文别名: N1-hydroxy-N8-phenethyloctanediamide；N'-hydroxy-N-(2-phenylethyl)octanediamide
• CAS: 408357-43-7
• 化学式: C₁₆H₂₄N₂O₃
• 分子量: 292.378
• InChiKey: CYDOMFOKDNLFNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  methyl 8-oxo-8-(phenethylamino)octanoate 在 sodium hydroxide 、 盐酸羟胺 作用下， 以 甲醇 、 水 为溶剂， 以30%的产率得到8-(hydroxyamino)-8-oxo-N-phenethyloctanamide
  参考文献：
  名称：

  Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2008.06.020

文献信息

• 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。
• Carbamic acid compounds comprising an amide linkage as HDAC inhibitors
  申请人：TopoTarget UK Limited

  公开号：EP2083005A1

  公开（公告）日：2009-07-29

  This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: 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: -NR1(=O)- and -C(=O)NR1-; R1 is an amido substituent; and, Q2 is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, and ethers thereof, for use in the treatment of a fibroproliferative disorder; liver fibrosis; smooth muscle proliferative disorder; atherosclerosis; restenosis; a neurodegenative disease; Alzheimer's; Parkinson's; Huntington's chorea; amyotropic lateral sclerosis; spino-cerebellar degeneration; an inflammatory disease; osteoarthritis; rheumatoid arthritis; a diseases involving angiogenesis; diabetic retinopathy; a haematopoietic disorder; anaemia; sickle cell anaemia; thalassaeimia; a fungal infection; a parasitic infection; trypanosomiasis; helminthiasis; a protozoal infection; a bacterial infection; a viral infection; a condition treatable by immune modulation; multiple sclerosis; autoimmune diabetes; lupus; atopic dermatitis; an allergy; asthma; allergic rhinitis; or inflammatory bowel disease.

  本发明涉及某些抑制 HDAC 活性的活性氨基甲酸化合物，其分子式如下： 其中A 是芳基；Q1 是芳基领导基团，其骨架至少有 2 个碳原子；J 是酰胺连接，选自-NR1(＝O)-和-C(＝O)NR1-；R1是氨基取代基；Q2是酸性领导基团；及其药学上可接受的盐、溶液剂、酰胺、酯和醚，用于治疗纤维增生性疾病；肝纤维化；平滑肌增生性疾病；动脉粥样硬化；再狭窄；神经变性疾病；阿尔茨海默氏症；帕金森氏症；亨廷顿舞蹈症；肌萎缩侧索硬化症；脊髓小脑变性；炎症性疾病；骨关节炎；类风湿性关节炎；血管生成疾病；糖尿病视网膜病变；造血障碍；贫血；镰状细胞性贫血；地中海贫血；真菌感染；寄生虫感染；锥虫病；蠕虫病；原虫感染、细菌感染、病毒感染、可通过免疫调节治疗的疾病、多发性硬化症、自身免疫性糖尿病、狼疮、特应性皮炎、过敏症、哮喘、过敏性鼻炎或炎症性肠病。
• US7569724B2
  申请人：——

  公开号：US7569724B2

  公开（公告）日：2009-08-04
• US7880020B2
  申请人：——

  公开号：US7880020B2

  公开（公告）日：2011-02-01
• 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.