N-hydroxy-N-(1-benzo[b]thien-3-ylethyl) urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: N-hydroxy-N-(1-benzo[b]thien-3-ylethyl) urea
• 英文别名: N-hydroxy-N-(1-benzo[b]thien-3-ylethyl)-urea；N-hydroxy-N-(1-benzo[b]thien-3-ylethyl)urea；N-[1-(1-benzothien-3-yl)ethyl]-N-hydroxyurea；1-[1-(1-benzothiophen-3-yl)ethyl]-1-hydroxyurea
• 化学式: C₁₁H₁₂N₂O₂S
• 分子量: 236.294
• InChiKey: AMMPGBYIKIGTPN-UHFFFAOYSA-N

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：

  1-benzo[b]thiophen-3-yl-ethanone oxime 在 盐酸 、 吡啶硼烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 2.17h， 生成 N-hydroxy-N-(1-benzo[b]thien-3-ylethyl) urea
  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

• Indole, benzofuran, benzothiophene containing lipoxygenase inhibiting
  申请人：Abbott Laboratories

  公开号：US04873259A1

  公开（公告）日：1989-10-10

  Compounds of the formula: ##STR1## wherein R.sub.1 is (1) hydrogen, (2) C.sub.1 to C.sub.4 alkyl, (3) C.sub.2 to C.sub.4 alkenyl, or (4) NR.sub.2 R.sub.3, wherein R.sub.2 and R.sub.3 are independently selected from (1) hydrogen, (2) C.sub.1 to C.sub.4 alkyl and (3) hydroxyl, but R.sub.2 and R.sub.3 are not simultaneously hydroxyl; wherein X is oxygen, sulfur, SO.sub.2, or NR.sub.4, wherein R.sub.4 is (1) hydrogen, (2) C.sub.1 to C.sub.6 alkyl, (3) C.sub.1 to C.sub.6 alkoyl, (4) aroyl, or (5) alkylsulfonyl; A is selected from C.sub.1 to C.sub.6 alkylene and C.sub.2 to C.sub.6 alkenylene; n is 1-5; Y is selected independently at each occurrence from (1) hydrogen, (2) halogen, (3) hydroxy, (4) cyano, (5) halosubstituted alkyl, (6) C.sub.1 to C.sub.12 alkyl, (7) C.sub.2 to C.sub.12 alkenyl, (8) C.sub.1 to C.sub.12 alkoxy, (9) C.sub.3 to C.sub.8 cycloalkyl, (10) C.sub.1 -C.sub.8 thioalkyl, (11) aryl, (12) aryloxy, (13) aroyl, (14) C.sub.1 to C.sub.12 arylalkyl, (15) C.sub.2 to C.sub.12 arylalkenyl, (16) C.sub.1 to C.sub.12 arylalkoxy, (17) C.sub.1 to C.sub.12 arylthioalkoxy, and substituted derivatives of (18) aryl, (19) aryloxy, (20) aroyl, (21) C.sub.1 to C.sub.12 arylalkyl, (22) C.sub.2 to C.sub.12 arylalkenyl, (23) C.sub.1 to C.sub.12 arylalkoxy, or (24) C.sub.1 to C.sub.12 arylthioalkoxy, wherein substituents are selected from halo, nitro, cyano, C.sub.1 to C.sub.12 alkyl, alkoxy, and halosubstituted alkyl; Z is oxygen or sulfur; and M is hydrogen, a pharmaceutically acceptable cation, aroyl, or C.sub.1 to C.sub.12 alkoyl, are potent inhibitors of 5- and/or 12-lipoxygenase enzymes. Also disclosed are lipoxygenase inhibiting compositions and a method for inhibiting lipoxygenase activity.

  该公式化合物为：##STR1## 其中 R.sub.1 为(1) 氢，(2) C.sub.1 到 C.sub.4 烷基，(3) C.sub.2 到 C.sub.4 烯基，或(4) NR.sub.2 R.sub.3，其中 R.sub.2 和 R.sub.3 分别选自(1) 氢，(2) C.sub.1 到 C.sub.4 烷基和(3) 羟基，但 R.sub.2 和 R.sub.3 不能同时为羟基；其中 X 为氧、硫、SO.sub.2 或 NR.sub.4，其中 R.sub.4 为(1) 氢，(2) C.sub.1 到 C.sub.6 烷基，(3) C.sub.1 到 C.sub.6 烷酰，(4) 芳酰基，或(5) 烷基磺酰基；A 选自 C.sub.1 到 C.sub.6 烷基和 C.sub.2 到 C.sub.6 烯基；n 为1-5；Y 在每次出现时独立选择自(1) 氢，(2) 卤素，(3) 羟基，(4) 氰基，(5) 卤代烷基，(6) C.sub.1 到 C.sub.12 烷基，(7) C.sub.2 到 C.sub.12 烯基，(8) C.sub.1 到 C.sub.12 烷氧基，(9) C.sub.3 到 C.sub.8 环烷基，(10) C.sub.1 -C.sub.8 硫代烷基，(11) 芳基，(12) 芳氧基，(13) 芳酰基，(14) C.sub.1 到 C.sub.12 芳基烷基，(15) C.sub.2 到 C.sub.12 芳基烯基，(16) C.sub.1 到 C.sub.12 芳基氧基，(17) C.sub.1 到 C.sub.12 芳基硫代烷氧基，以及取代衍生物(18) 芳基，(19) 芳氧基，(20) 芳酰基，(21) C.sub.1 到 C.sub.12 芳基烷基，(22) C.sub.2 到 C.sub.12 芳基烯基，(23) C.sub.1 到 C.sub.12 芳基氧基，或(24) C.sub.1 到 C.sub.12 芳基硫代烷氧基，其中取代基选自卤素、硝基、氰基、C.sub.1 到 C.sub.12 烷基、烷氧基和卤代烷基；Z 为氧或硫；M 为氢、药用可接受阳离子、芳酰基或 C.sub.1 到 C.sub.12 烷酰，是 5-和/或 12-脂氧酶酶的有效抑制剂。还公开了抑制脂氧酶活性的化合物和抑制脂氧酶活性的方法。
• Combination of dehydroepiandrosterone or dehydroepiandrosterone-sulfate with a lipoxygenase inhibitor for treatment of asthma or chronic obstructive pulmonary disease
  申请人：Robinson B. Cynthia

  公开号：US20050090455A1

  公开（公告）日：2005-04-28

  A pharmaceutical or veterinary composition, comprises a first active agent selected from a dehydroepiandrosterone and/or dehydroepiandrosterone-sulfate, or a salt thereof, and a second active agent comprising a lipoxygenase inhibitor for the treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases. The composition is provided in various formulations and in the form of a kit. The products of this patent are applied to the prophylaxis and treatment of asthma, chronic obstructive pulmonary disease, or other respiratory diseases.

  一种药物或兽药组合物，包括从去氢表雄酮和/或去氢表雄酮硫酸盐中选择的第一活性成分，以及包括一种脂氧合酶抑制剂的第二活性成分，用于治疗哮喘、慢性阻塞性肺病或其他呼吸系统疾病。该组合物以各种配方形式提供，并以套装形式提供。该专利的产品用于预防和治疗哮喘、慢性阻塞性肺病或其他呼吸系统疾病。
• ACID-CATALYZED ADDITION OF<i>N</i>-HYDROXYUREA TO 1-ARYL ALCOHOL DERIVATIVES: A NEW SYNTHESIS OF ZILEUTON
  作者：Richard R. Copp、Brian T. Fohey、Gregory Lannoye

  DOI：10.1081/scc-100105880

  日期：2001.1

  A highly efficient synthesis of Zileuton is described in which the key step involves a site-specific alkylation of hydroxyurea under acid catalysis. Various aryl alcohol electrophiles were tested and the reaction was found to be highly substrate-specific, favoring benzothiophene and benzofuran-based alcohols.

  描述了齐留通的高效合成，其中关键步骤涉及在酸催化下羟基脲的位点特异性烷基化。测试了各种芳醇亲电试剂，发现该反应具有高度的底物特异性，有利于苯并噻吩和苯并呋喃基醇。
• Pharmaceutical composition for treating multiple sclerosis
  申请人：Neu Ingo

  公开号：US20050020665A1

  公开（公告）日：2005-01-27

  Use of a compound of the general formula I and/or a pharmaceutically acceptable salt thereof as active ingredient for the preparation of a pharmaceutical composition for the treatment of multiple sclerosis in humans: wherein X represents NCH 3 , O or S. A represents an unsubstituted C 1-4 alkylene or a substituted C 1-4 alkylene that is mono- or poly-substituted with substituents independently selected from CH 3 , CH 2 CH 3 , CH 2 CH 2 CH 3 und CH(CH 3 ) 2 , M represents H; benzoyl; unsubstituted C 1-12 alkanoyl; substituted C 1-12 alkanoyl that is mono- or poly-substituted with substituents independently selected from CH 3 , CH 2 CH 3 , F and Cl; unsubstituted C 1-12 alkyl; or substituted C 1-12 alkyl that is mono- or poly-substituted with substituents independently selected from CH 3 , CH 2 CH 3 , F and Cl; R represents CH 3 , CH 2 CH 3 or NR 1 R 2 , wherein R 1 and R 2 independently represent H, CH 3 or CH 2 CH 3 , and Y 1 , Y 2 and Y 3 are independently selected from H, CH 3 , CH 2 CH 3 , F and Cl.

  将通式 I 的化合物和/或其药学上可接受的盐作为活性成分，用于制备治疗人类多发性硬化症的药物组合物： 其中 X 代表 NCH 3 、O 或 S。 A 代表未取代的 C 1-4 烯或取代的 C 1-4 烯，其取代基为单取代基或多取代基，取代基独立选自 CH 3 、CH 2 CH 3 , CH 2 CH 2 CH 3 和 CH(CH 3 ) 2 , M 代表 H；苯甲酰基；未取代的 C 1-12 烷酰基；取代的 C 1-12 取代的 C 1-12 烷酰基，该烷酰基被独立选自 CH 3 、CH 2 CH 3 、F 和 Cl；未取代的 C 1-12 烷基；或取代的 C 1-12 烷基，其取代基为单取代基或多取代基，取代基独立选自 CH 3 、CH 2 CH 3 F 和 Cl； R 代表 CH 3 、CH 2 CH 3 或 NR 1 R 2 其中 R 1 和 R 2 分别代表 H、CH 3 或 CH 2 CH 3 和 Y 1 , Y 2 和 Y 3 独立选自 H、CH 3 、CH 2 CH 3 F 和 Cl。
• Indole, benzofuran, benzothiophene containing lipoxygenase inhibiting compounds
  申请人：ABBOTT LABORATORIES

  公开号：EP0279263B1

  公开（公告）日：1993-08-04