N-{3-[5-(4-fluorophenylmethyl)-thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea | 154355-75-6

• 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: N-{3-[5-(4-fluorophenylmethyl)-thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea
• 英文别名: N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea；N-(4-(5-(4-fluorobenzyl)thien-2-yl)but-3-yn-2-yl)-N-hydroxyurea；atreleuton；N-[3-[5-(4-fluorophenylmethyl)-thien-2-yl]-1-methyl-2-propynyl]-N-hydroxyurea；N-[3-[5-(4-fluorophenylmethyl)-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea；N-{3-[5-(4-fluorophenylmethyl)-2-thienyl]-1-methyl-2-propynyl}-N-hydroxyurea；Cox/5-LO-IN-1；1-[4-[5-[(4-fluorophenyl)methyl]thiophen-2-yl]but-3-yn-2-yl]-1-hydroxyurea
• CAS: 154355-75-6
• 化学式: C₁₆H₁₅FN₂O₂S
• 分子量: 318.372
• InChiKey: MMSNEKOTSJRTRI-UHFFFAOYSA-N

物化性质

• 沸点：
  506.7±60.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  94.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  存储条件：2-8°C，密封保存，干燥环境。

制备方法与用途

生物活性

COX/5-LO-IN-1 (Atreleuton analog) 是一种用于研究炎症性和过敏性疾病的 cylooxygenase 和 5-lipoxygenase (5-LO) 的抑制剂。

靶点

5-LO	2 μM (IC50)
COX	-

体外研究

COX/5-LO-IN-1 能减少白三烯 B4、C4、D4 和 E4，以及前列腺素和血栓烷等环氧化酶产物的生物合成。这种化合物在人类全血中对 5-脂氧合酶表现出抑制活性，IC₅₀ 值为 0.2 μM，并且在治疗炎症和过敏性疾病方面具有重要作用。

反应信息

• 作为反应物：
  描述：

  萘普生 、 N-{3-[5-(4-fluorophenylmethyl)-thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea 以 二氯甲烷 为溶剂， 以2.6 g (74%)的产率得到N-[(S)-2-(6-methoxynaphth-2-yl)propionyloxy]-N-[3-(5-(4-fluorophenylmethyl)thien-2-yl)-(R)-1-methyl-2-propynyl]urea
  参考文献：
  名称：

  Lipoxygenase and cyclooxygenase inhibiting compounds

  摘要：

  具有上述结构##STR1##或其药用可接受盐的化合物具有作为环氧合酶和5-脂氧合酶的抑制剂的活性，可减少白三烯B.sub.4、C.sub.4、D.sub.4和E.sub.4以及环氧合酶产物如前列腺素和血栓素的生物合成，并可用于治疗炎症和过敏疾病状态。这些化合物具有上述指示的结构，其中A选自(a)可选择地取代的碳环芳基、(b)可选择地取代的呋喃基、(c)可选择地取代的苯并[b]呋喃基、(d)可选择地取代的噻吩基、(e)可选择地取代的吡啶氧基、(f)可选择地取代的吡啶基烷基、(g)可选择地取代的苯并[b]噻吩基、(h)可选择地取代的吡啶基、(i)可选择地取代的喹啉基，和(j)可选择地取代的吲哚基；X选自(a)可选择地取代的烷基、(b)可选择地取代的烯基，和(c)可选择地取代的炔基；R.sup.1和R.sup.2各自选自氢、羟基和烷基；Z是一种非类固醇抗炎药的一般公式Z--COOH的残基。

  公开号：

  US05516789A1
• 作为产物：
  描述：

  2-(4-氟苄基)噻吩 在 哌啶 、 ammonium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 、 四(三苯基膦)钯 、 偶氮二甲酸二异丙酯 、 溶剂黄146 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 2.0h， 生成 N-{3-[5-(4-fluorophenylmethyl)-thien-2-yl]-1-methyl-2-propynyl}-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

文献信息

• [(Substituted) phenyalkyl]furylalkynyl-and [substituted) phenyalkyl]
  申请人：Abbott Laboratories

  公开号：US05288751A1

  公开（公告）日：1994-02-22

  The present invention relates to compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein Z is selected from optionally substituted phenyl, furyl, thienyl or thiazolyl; which inhibits leukotriene biosynthesis and is useful in the treatment of inflammatory disease states; also disclosed are leukotriene biosynthesis inhibiting compositions and a method for inhibiting 5-lipoxygenase activity and leukotriene biosynthesis.

  本发明涉及以下式的化合物##STR1##及其药用可接受的盐，其中Z选自可选择的取代苯基、呋喃基、噻吩基或噻唑基；该化合物抑制白三烯生物合成，在治疗炎症性疾病状态中有用；还公开了抑制白三烯生物合成的组合物和抑制5-脂氧合酶活性和白三烯生物合成的方法。
• PHENYLALKYL N-HYDROXYUREAS FOR TREATING LEUKOTRIENE RELATED PATHOLOGIES
  申请人：Taub Rebecca

  公开号：US20130190514A1

  公开（公告）日：2013-07-25

  The method of treating patients by administering N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea for treatment of leukotriene related pathologies, and compositions for this use.

  通过给予N-[3-[5-[(4-氟苯基)甲基]-2-噻吩基]-1-甲基-2-丙炔基]-N-羟基脲来治疗白三烯相关病理的方法，以及用于此用途的组合物。
• Substituted aryl- and heteroarylalkenyl-N-hydroxyurea inhibitors of
  申请人：Abbott Laboratories

  公开号：US05506261A1

  公开（公告）日：1996-04-09

  Compounds of the structure ##STR1## wherein Z is selected from optionally substituted thienyl, thiazolyl, oxazolyl and furyl 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Z选自可选取代的噻吩基、噻唑基、噁唑基和呋喃基，是脂氧合酶酶的强效抑制剂，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是有用的。
• Polynucleotide binding complexes comprising sterols and saponin
  申请人：Nordic Vaccine Technology A/S

  公开号：EP2011517A1

  公开（公告）日：2009-01-07

  The present invention pertains to complexes comprising sterols and saponins. The complexes are capable of binding a genetic determinant including a polynucleotide. The complexes may further comprise a lipophilic moiety, optionally a lipophilic moiety comprising a contacting group and/or a targeting ligand, and/or a saccharide moiety. The complexes may further comprise an immunogenic determinant and/or an antigenic determinant and/or a medicament and/or a diagnostic compound. The complexes may in even further embodiments be encapsulated by an encapsulation agent including a biodegradable microsphere. The present invention also pertains to pharmaceutical compositions and methods of treatment of an individual by therapy and/or surgery, methods of cosmetic treatment, and diagnostic methods practised on the human or animal body.

  本发明涉及由甾醇和皂甙组成的复合物。这些复合物能够结合包括多核苷酸在内的遗传决定因子。复合物可进一步包含亲脂分子，可选择包含接触基团和/或靶向配体的亲脂分子和/或糖分子。复合物可进一步包括免疫原决定簇和/或抗原决定簇和/或药物和/或诊断化合物。在更进一步的实施方案中，复合物可被包括生物可降解微球在内的封装剂封装。本发明还涉及通过治疗和/或手术对个体进行治疗的药物组合物和方法、美容治疗方法以及对人体或动物体进行诊断的方法。
• Genetic susceptibility variants associated with cardiovascular disease
  申请人：Decode Genetics EHF

  公开号：EP2471954A1

  公开（公告）日：2012-07-04

  The invention relates to methods of diagnosing susceptibility to cardivascular disease, including coronary artery disease, MI, abdominal aorta aneurysm, intracranial aneurysm restenosis and peripheral arterial disease, by assessing the presence or absence of alleles of certain polymorphic markers found to be associated with cardiovascular disease. The invention further relates to kits encompassing reagents for assessing such markers, and methods for assessing the probability of response to therapeutic agents and methods using such markers.

  本发明涉及通过评估发现与心血管疾病相关的某些多态性标记物等位基因的存在与否来诊断心血管疾病易感性的方法，包括冠状动脉疾病、心肌梗塞、腹主动脉瘤、颅内动脉瘤再狭窄和外周动脉疾病。本发明还涉及包括用于评估此类标记物的试剂盒，以及评估对治疗剂的反应概率的方法和使用此类标记物的方法。