1-[4-[5-(4-氟苯氧基)呋喃-2-基]丁-3-炔-2-基]-1-羟基脲 | 141579-67-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-[4-[5-(4-氟苯氧基)呋喃-2-基]丁-3-炔-2-基]-1-羟基脲
• 英文名称: A-78773
• 英文别名: N-hydroxy-N-{4-[5-(4-fluorophenoxy)-2-furyl]-3-butyn-2yl}urea；N-{3-[5-(4-fluorophenoxy)fur-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea；N-hydroxy-N-{4-[5-(4-fluorophenoxy)-furan-2-yl]-3-butyn-2yl}urea；N-Hydroxy-N-(4-(5-(4-fluorophenoxy)-2-furyl)-3-butyn-2-yl)urea；1-[4-[5-(4-fluorophenoxy)furan-2-yl]but-3-yn-2-yl]-1-hydroxyurea
• CAS: 141579-67-1
• 化学式: C₁₅H₁₃FN₂O₄
• 分子量: 304.278
• InChiKey: OLZHFFKRBCZHHT-UHFFFAOYSA-N

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

反应信息

• 作为反应物：
  描述：

  1-[4-[5-(4-氟苯氧基)呋喃-2-基]丁-3-炔-2-基]-1-羟基脲 在 Pd-BaSO₄ 氢气 作用下， 以 喹啉 、 乙醇 、 乙酸乙酯 为溶剂， 反应 0.5h， 以25%的产率得到(Z)-N-{3-[5-(4-fluorophenoxy)-2-furyl]-1-methyl-2-propenyl}-N-hydroxyurea
  参考文献：
  名称：

  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.

  摘要：

  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.

  DOI：

  10.1021/jm00024a004
• 作为产物：
  描述：

  2-<5-(4-fluorophenoxy)-2-furyl>-1,1-dibromoethene 在 正丁基锂 、 偶氮二甲酸二异丙酯 、 氨 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.5h， 生成 1-[4-[5-(4-氟苯氧基)呋喃-2-基]丁-3-炔-2-基]-1-羟基脲
  参考文献：
  名称：

  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.

  摘要：

  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.

  DOI：

  10.1021/jm00024a004

文献信息

• TARGETED NITROXIDE AGENTS
  申请人：Wipf Peter

  公开号：US20100035869A1

  公开（公告）日：2010-02-11

  Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation.

  本文提供了一种对自由基清除有用的组合物和相关方法，具有特定选择性作用于线粒体。这些化合物包括一个连接到线粒体靶向基团的亚硝基含有基团。这些化合物可以交联成二聚体而不丧失活性。本文还提供了一种用于预防、缓解和治疗辐射引起的损伤的方法。该方法包括向患者输送一种如本文所述的化合物，以有效地预防、缓解或治疗辐射引起的损伤。
• Substituted 2,3-dihydroisoxazoles (Δ4-isoxazolines) via palladium-mediated cyclization of propargylic N-hydroxyureas
  作者：Eric J. Stoner、Brian A. Roden、Sanjay Chemburkar

  DOI：10.1016/s0040-4039(97)01080-0

  日期：1997.7

  Aryl-substituted propargylic N-hydroxyreas cyclize in the presence of catalytic Pd(OAc)2 to yield 2,3-dihydroisoxazoles.

  芳基取代的炔丙基N-羟基reas在催化Pd（OAc）2的存在下环化，生成2,3-二氢异恶唑。
• TOPICAL FORMULATIONS OF TARGETED NITROXIDE AGENTS
  申请人：Falo, JR. Louis D.

  公开号：US20120207687A1

  公开（公告）日：2012-08-16

  A method for preventing or treating skin damage in a radiotherapy subject, comprising topically administering to the subject a composition that includes a therapeutically effective amount at least one targeted nitroxide agent and at least one additional ingredient.

  一种用于预防或治疗放疗受试者皮肤损伤的方法，包括将至少一种靶向亚硝酰胺试剂和至少一种其他成分的治疗有效剂量的组合物局部施用于受试者的皮肤。
• 2, 4-PYRIMIDINEDIAMINE COMPOUNDS AND PRODRUGS THEREOF AND THEIR USES
  申请人：Yu Jiaxin

  公开号：US20110251177A1

  公开（公告）日：2011-10-13

  The present disclosure provides biologically active 2,4-pyrimidinediamine compounds of formulae (I) and (II): and salts thereof, compositions comprising these compounds, and methods of using these compounds in a variety of applications.

  本公开提供生物活性的2,4-嘧啶二胺化合物，其分别具有以下式子（I）和（II）：以及它们的盐、包含这些化合物的组合物，以及这些化合物在各种应用中的使用方法。
• Acetylene derivatives having lipoxygenase inhibitory activity
  申请人：Abbott Laboratories

  公开号：US05476873A1

  公开（公告）日：1995-12-19

  Compounds of the structure ##STR1## where p and q are zero or one, but cannot both be the same, M is a pharmaceutically acceptable cation or a metabolically cleavable group, B is a valence bond or a straight or branched alkylene group, R is alkyl, cycloalkyl or --NR.sup.1 R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl or alkanoyl, and A is optionally substituted carbocyclic aryl, furyl, benzo[b]furyl, thienyl, or benzo[b]thienyl are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

  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。