A-79175 | 141579-87-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: A-79175
• 英文别名: (R)-(+)-N-(4-(5-(4-fluorophenoxy)-2-furyl)-3-butyn-2-yl)-N-hydroxyurea；(R)-(+)-N-<3-<5-(4-fluorophenoxy)methyl>-2-furyl>-1-methyl-2-propynyl-N-hydroxyurea；R(+)-N-[3-[5-(4-fluorophenoxy)-2-furanyl]-1-methyl-2-propynyl]-N-hydroxyurea；1-[(2R)-4-[5-(4-fluorophenoxy)furan-2-yl]but-3-yn-2-yl]-1-hydroxyurea
• CAS: 141579-87-5
• 化学式: C₁₅H₁₃FN₂O₄
• 分子量: 304.278
• InChiKey: OLZHFFKRBCZHHT-SNVBAGLBSA-N

物化性质

• 沸点：
  472.9±55.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  88.9
• 氢给体数：
  2
• 氢受体数：
  5

制备方法与用途

79175是一种5-脂氧合酶抑制剂，能够促进骨形成。

反应信息

• 作为产物：
  描述：

  1-[4-[5-(4-氟苯氧基)呋喃-2-基]丁-3-炔-2-基]-1-羟基脲 生成 A-79175
  参考文献：
  名称：

  Acetylene derivatives having lipoxygenase inhibitory activity

  摘要：

  结构式为## STR1 ##的化合物，其中p和q为零或一，但不能同时相同，M是药学上可接受的阳离子或代谢可裂解基团，B是价键或直链或支链烷基，R是烷基，环烷基或--NR.sup.1 R.sup.2，其中R.sup.1和R.sup.2是氢，烷基，环烷基或烷酰基，而A是可选的取代的碳环芳基，呋喃基，苯并[b]呋喃基，噻吩基或苯并[b]噻吩基是脂氧合酶酶的强力抑制剂，从而抑制白三烯的生物合成。这些化合物在治疗或改善过敏和炎症疾病状态方面有用。

  公开号：

  US05476873A1

文献信息

• Asymmetric synthesis of (R)-N-3-butyn-2-yl-N-hydroxyurea, a key intermediate for 5-lipoxygenase inhibitors
  作者：Teodozyj Kolasa、Andrew O. Stewart、Clint D.W. Brooks

  DOI：10.1016/0957-4166(96)00068-7

  日期：1996.3

  An efficient asymmetric synthesis of (R)-N-3-butyn-2-yl-N-hydroxyurea from crotyl alcohol is described. The process involves asymmetric Sharpless epoxidation to establish the stereochemistry, formation of (S)-3-butynol and hydroxyl substitution with inversion by the masked N-hydroxyurea reagent N,O-bis(phenoxycarbonyl)hydroxylamine in a Mitsunobu reaction.

  描述了从巴豆醇有效地不对称合成（R）-N -3-丁炔-2-基-N-羟基脲。该方法涉及不对称的Sharpless环氧化，以建立立体化学，形成（S）-3-丁炔醇，并通过Mitsunobu反应中被掩蔽的N-羟基脲试剂N，O-双（苯氧基羰基）羟胺转化而进行羟基取代。
• ETHER DERIVATIVES USEFUL AS INHIBITORS OF PDE4 ISOZYMES
  申请人：Marfat Anthony

  公开号：US20070161681A1

  公开（公告）日：2007-07-12

  Compounds useful as inhibitors of PDE4 in the treatment of diseases regulated by the activation and degranulation of eosinophils, especially asthma, chronic bronchitis, and chronic obstructive pulmonary disease, of the formula: wherein the substituents are as defined in the specification.

  以下化合物可用作PDE4的抑制剂，用于治疗由嗜酸性粒细胞的活化和脱颗粒调控的疾病，特别是哮喘、慢性支气管炎和慢性阻塞性肺疾病，其化学式如下：其中取代基如规范中所定义。
• Combination for the treatment of airway disorders
  申请人：Hanauer Guido

  公开号：US20050165041A1

  公开（公告）日：2005-07-28

  The invention relates to the combination of proton pump inhibitors and airway therapeutics for the treatment of airway disorders.

  本发明涉及质子泵抑制剂和气道治疗剂的组合，用于治疗气道疾病。
• Preparation of (R)-(+)-N-[3-[5-[(4-Fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor.
  作者：Clint D. W. Brooks、Andrew O. Stewart、Anwer Basha、Pramila Bhatia、James D. Ratajczyk、Jonathan G. Martin、Richard A. Craig、Teodozyj Kolasa、Jennifer B. Bouska、Carmine Lanni、Richard R. Harris、Peter E. Malo、George W. Carter、Randy L. Bell

  DOI：10.1021/jm00024a004

  日期：1995.11

  Structure-activity optimization of inhibitory potency and duration of action of N-hydroxyurea containing 5-lipoxygenase inhibitors was conducted. The lipophilic heteroaryl template and the link group connnecting the template to the N-hydroxyurea pharmacophore were modified. Inhibition of 5-lipoxygenase was evaluated in vitro in a human whole blood assay. An in vitro assay using liver microsomes from monkey was used to evaluate congeners for comparative rates of glucuronidation. (3-Heteroaryl-1-methyl-2-propynyl)-N-hydroxyureas were found to be more resistant to in vitro glucuronidation. The promising inhibitor N-[3-[5-(4-fluorophenoxy)2-furyl]-1-methyl-2-propynyl]-N-hydroxyurea (6) was found to have stereoselective glucuronidation in monkey and man. The R enantiomer 7 provided longer duration of inhibition as evaluated by an ex vivo whole blood assay. Further optimization of the lipophilic template led to the discovery of (R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (11) with more effective and prolonged inhibition of leukotriene biosynthesis than zileuton (1) and 7 in monkey and man. The optimized 5-lipoxygenase inhibitor 11 was selected for development as an investigational drug for leukotriene-mediated disorders.
• Synthesis of A-79175: a second generation 5-lipoxygenase inhibitor
  作者：Daniel A. Dickman、Yi-Yin Ku、Howard E. Morton、Sanjay R. Chemburkar、Hemantkumar H. Patel、Albert Thomas、Daniel J. Plata、David P. Sawick

  DOI：10.1016/s0957-4166(97)00159-6

  日期：1997.6

  A convergent, high yielding, and scalable synthesis of A-79175, with a key step involving a mild and efficient Cu-Pd catalyzed coupling reaction of a terminal acetylene with a substituted 2-iodofuran is discussed. (C) 1997 Elsevier Science Ltd.