1-[(1R)-1-(1-苯并噻吩-2-基)乙基]-1-羟基脲 | 142606-21-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 中文名称: 1-[(1R)-1-(1-苯并噻吩-2-基)乙基]-1-羟基脲
• 英文名称: (+)-Zileuton
• 英文别名: (R)-(+)-N-[1-(benzo[b]thiophen-2-yl)ethyl]-N-hydroxy-urea；(+)-(R)-Zileuton；zileuton；(+)-(R)-1-(1-benzo[b]thien-2-ylethyl)-1-hydroxyurea；(R)-(+)-1-(1-benzo[b]thien-2-ylethyl)-1-hydroxyurea；Zileuton, (R)-；1-[(1R)-1-(1-benzothiophen-2-yl)ethyl]-1-hydroxyurea
• CAS: 142606-21-1
• 化学式: C₁₁H₁₂N₂O₂S
• 分子量: 236.294
• InChiKey: MWLSOWXNZPKENC-SSDOTTSWSA-N

物化性质

• 熔点：
  148-149 °C
• 沸点：
  449.4±47.0 °C(Predicted)
• 密度：
  1.401±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  94.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  齐留通 生成 1-[(1R)-1-(1-苯并噻吩-2-基)乙基]-1-羟基脲
  参考文献：
  名称：

  Structure−Activity Relationships of N-Hydroxyurea 5-Lipoxygenase Inhibitors

  摘要：

  The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure-activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N-[3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hy- droxyurea (17c) was identified and selected for clinical development.

  DOI：

  10.1021/jm9700474

文献信息

• Asymmetric synthesis of N-1-(heteroaryl)ethyl-N-hydroxyureas
  作者：Mariusz J. Bosiak、Marek P. Krzemiński、Parasuraman Jaisankar、Marek Zaidlewicz

  DOI：10.1016/j.tetasy.2008.03.026

  日期：2008.5

  The asymmetric synthesis of two 5-lipoxygenase inhibitors (R)-N-1-(benzofuran-2-yl)ethyl-N-hydroxyurea, 99% ee, and (R)-N-1-(benzo[b]thiophen-2-yl)ethyl-N-hydroxyurea, 95% ee, is described. The enantioselective reduction of 1-(benzofuran-2-yl)ethanone oxime O-benzyl ether and 1-(benzo[b]thiophen-2-yl)ethanone oxime O-benzyl ether with borane oxazaborolidine, generated from (1R,2S,3R,4S)-3-amino-1,7

  两种5-脂氧合酶抑制剂（R）-N -1-（苯并呋喃-2-基）乙基-N-羟基脲，99％ee和（R）-N -1-（苯并[ b ]噻吩-描述了95％ee的2-基）乙基-N-羟基脲。用（1 R，2）生成的硼烷恶唑硼烷将对（1-苯并呋喃-2-基）乙酮肟O-苄基醚和1-（苯并[ b ]噻吩-2-基）乙酮肟O-苄基醚进行对映选择性还原硫，3 R，4 S）-3-氨基-1,7,7-三甲基双环[2.2.1]庚-2-醇被用于形成立体异构中心。
• Synthesis of chiral zileuton, a potent and selective inhibitor of 5-lipoxygenase
  作者：Chi-Nung Hsiao、Teodozyj Kolasa

  DOI：10.1016/s0040-4039(00)79043-5

  日期：1992.5

  Coupling and intramolecular Wittig reaction of N-benzyloxy-D-alanine anhydride (13) and (2-Mercaptophenyl)methyltriphenylphosphonium bromide (3) were used as key steps to prepare (+)-enantiomer of zileuton (1), a potent and selective inhibitor of 5-lipoxygenase.

  N-苄氧基-D-丙氨酸酐（13）和（2-巯基苯基）甲基三苯基溴化（（3）的偶联和分子内Wittig反应被用作制备齐留通（1）的（+）-对映体的关键步骤，齐留通（1）是一种有效且选择性的5-脂氧合酶的抑制剂。
• New crystal form and pharmaceutical compositions of (+)-R-zileuton
  申请人：Critical Therapeutics, Inc.

  公开号：EP2409973A1

  公开（公告）日：2012-01-25

  A crystalline form of (+)-R-zileuton, which may be used in pharmaceutical applications, is disclosed, characterized by a variety of properties and physical measurements. As well, methods of producing crystalline (+)-R-zileuton, and using it to inhibit 5-lipoxygenase activity in subjects to treat a number of diseases, are also discussed.

  本研究公开了一种可用于制药的 (+)-R-zileuton 结晶形式，其特点是具有多种特性和物理测量值。此外，还讨论了生产结晶型 (+)-R-zileuton 的方法，以及用它来抑制受试者体内 5-脂氧合酶的活性以治疗多种疾病。
• USE OF ZILEUTON FOR THE TREATMENT OF NASAL POLYPS IN CYSTIC FIBROSIS PATIENTS
  申请人：Cornerstone Therapeutics Inc.

  公开号：EP2959899A1

  公开（公告）日：2015-12-30

  The present invention provides methods of treating nasal polyps in cystic fibrosis patients using zileuton. The present invention also provides methods of treating nasal polyps in cystic fibrosis patients using zileuton in combination with surgical debridement and/or steroid treatment.

  本发明提供了使用齐来顿治疗囊性纤维化患者鼻息肉的方法。本发明还提供了使用齐留通结合手术清创和/或类固醇治疗囊性纤维化患者鼻息肉的方法。
• TOPICAL ANTI-INFLAMMATORY PHARMACEUTICAL COMPOSITION WITH ZILEUTON CREAM FORMULATION
  申请人：Qurient Co. Ltd.

  公开号：EP3064197A1

  公开（公告）日：2016-09-07

  Provided herein is a zileuton cream type topical anti-inflammatory pharmaceutical composition, and more particularly, a zileuton cream type topical anti-inflammatory pharmaceutical composition capable of retaining stability at room temperature and of being applied topically to maximize medical effects while minimizing absorption to an entirety of body, thereby minimizing toxicity caused by the compound so as to be suitable to topical treatment of skin diseases caused by leukotriene.

  本文提供的是一种齐留通乳膏型外用消炎药物组合物，更具体地说，是一种齐留通乳膏型外用消炎药物组合物，该组合物能够在室温下保持稳定，外用时能够最大限度地发挥医疗效果，同时最大限度地减少全身吸收，从而最大限度地减少化合物引起的毒性，以适用于由白三烯引起的皮肤病的外用治疗。