6-acetoamido-3,5-dimethyl benzisoxazole | 515138-49-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 英文名称: 6-acetoamido-3,5-dimethyl benzisoxazole
• 英文别名: 6-acetamido-3,5-dimethyl-1,2-benzisoxazole；N-(3,5-dimethylbenzo[d]isoxazol-6-yl)acetamide；N-(3,5-dimethylbenzisoxazol-6-yl)acetamide；N-(3,5-Dimethyl-1,2-benzoxazol-6-yl)acetamide
• CAS: 515138-49-5
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: MHKMHMYPIIUJGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-acetoamido-3,5-dimethyl benzisoxazole 在 盐酸 、 水 、 溶剂黄146 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 24.92h， 生成 6-amino-3-[2-[4-isopropyl-2-[4-(trifluoromethyl)phenyl]-5-thiazolyl]ethyl]-5-methyl-1,2-benzisoxazole
  参考文献：
  名称：

  Biological evaluation of novel benzisoxazole derivatives as PPARδ agonists

  摘要：

  We discovered novel peroxisome proliferator-activated receptor delta agonists with a characteristic benzisoxazole ring. Compound 5 exhibited potent human PPAR delta transactivation activity. Furthermore, it stimulated the differentiation of oligodendrocyte precursor cells in vitro. This indicates that this potential drug may be effective for the treatment of demyelinating disorders such as multiple sclerosis. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.053
• 作为产物：
  描述：

  在 吡啶 作用下， 以86%的产率得到6-acetoamido-3,5-dimethyl benzisoxazole
  参考文献：
  名称：

  Synthesis of a novel human PPARδ selective agonist and its stimulatory effect on oligodendrocyte differentiation

  摘要：

  We successfully synthesized a novel peroxisome proliferator-activated receptor (PPAR)delta selective agonist, namely, compound 20, with a characteristic benzisoxazole ring. Compound 20 exhibited potent human PPAR delta transactivation activity and high d selectivity. Further, it stimulated differentiation of primary oligodendrocyte precursor cells in vitro, indicating that it may be an effective drug in the treatment of demyelinating disorders such as multiple sclerosis. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.11.030

文献信息

• Activator of peroxisome proliferator-activated receptor delta
  申请人：Sakuma Shogo

  公开号：US20070027196A1

  公开（公告）日：2007-02-01

  A compound represented by the formula (I) or a salt of the compound, and a PPAR-δ activator which contains the compound or salt as the active ingredient: (wherein A represents O or S; B 1 represents N, etc.; B 2 represents O, etc.; each of X 1 and X 2 represents O, S, a bond, etc.; Y represents C 1-8 alkylene chain; z represents O or S; R 1 represents aryl, etc. which can have substituents; R 2 represents C 1-8 alkyl, etc.; R 3 represents C 1-8 alkyl, C 2-8 alkenyl, etc.; each of R 4 and R 5 represents hydrogen, C 1-8 alkyl, etc.; and R 6 represents hydrogen, etc.; provided that each of Z and R 3 is attached to the benzene ring, and X 2 is not attached to the benzene ring).

  化合物的化学式为(I)或该化合物的盐，以及含有该化合物或盐为活性成分的PPAR-δ激动剂：（其中A代表O或S；B1代表N等；B2代表O等；X1和X2分别代表O、S、键等；Y代表C1-8烷基链；z代表O或S；R1代表苯基等，可以有取代基；R2代表C1-8烷基等；R3代表C1-8烷基、C2-8烯基等；R4和R5分别代表氢、C1-8烷基等；R6代表氢等；但要求Z和R3均连接到苯环上，且X2未连接到苯环上）。
• Activator for Peroxisome Proliferator Activated Receptor
  申请人：Sakuma Shogo

  公开号：US20100029949A1

  公开（公告）日：2010-02-04

  A compound having the following formula (II) or its salt is used as an activator for PPAR δ: [in which W 3 is a nitrogen atom or CH; Z 1 is an oxygen atom or a sulfur atom; each of R 11 and R 12 is a hydrogen atom, a halogen atom, a C 1 -C 8 alkyl group, a C 1 -C 8 alkoxy group, a C 1 -C 8 alkyl group having a halogen substituent, or the like; each of R 13 and R 14 is a hydrogen atom or a C 1 -C 8 alkyl group; A 1 is pyrazole or thiophene which may have a substituent; and m is an integer of 2 to 4].

  具有以下化学式（II）或其盐的化合物用作PPARδ的激活剂：[其中W3是氮原子或CH; Z1是氧原子或硫原子; R11和R12中的每一个是氢原子，卤素原子，C1-C8烷基，C1-C8烷氧基，具有卤素取代基的C1-C8烷基或类似物; R13和R14中的每一个是氢原子或C1-C8烷基; A1是吡唑或噻吩，可以具有取代基; m是2到4的整数]。
• ACTIVATING AGENT FOR PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR
  申请人：Sakuma Shogo

  公开号：US20110098480A1

  公开（公告）日：2011-04-28

  A compound represented by the formula (I) or a pharmacologically acceptable salt thereof is used as an activator of PPAR. wherein each of R 1 and R 2 is hydrogen, C 1-8 alkyl, C 1-8 alkyl substituted with halogen, or the like; each of R 3 , R 4 , R 5 , and R 6 is hydrogen, C 1-8 alkyl, or the like; X is sulfur or the like; Y is oxygen, a bond, or the like; p is 0 or 1; A is oxygen, CH 2 , N—NH 2 , or the like; when p is 1, B is phenyl, which can have a substituent; when p is 0, B is a condensed ring such as benzisoxazole, which can have a substituent; m is an integer of 1 to 4; and n is an integer of 0 to 5.

  化合物(I)或其药理学上可接受的盐被用作PPAR的激活剂，其中R1和R2中的每一个都是氢、C1-8烷基、以卤素取代的C1-8烷基或类似物；R3、R4、R5和R6中的每一个都是氢、C1-8烷基或类似物；X是硫或类似物；Y是氧、键或类似物；p为0或1；A是氧、CH2、N—NH2或类似物；当p为1时，B是苯基，可以有取代基；当p为0时，B是类似苯并异噁唑的融合环，可以有取代基；m是1至4的整数；n是0至5的整数。
• Use of PPAR Delta Ligands for the Treatment or Prevention of Inflammation or Energy Metabolism/Production Related Diseases
  申请人：Barbaras Ronald

  公开号：US20110092517A1

  公开（公告）日：2011-04-21

  Provided herein are methods for treatment, prevention, or amelioration of one or more symptoms of a disease or condition related to disorders of insulin and/or glucose metabolism, inflammatory conditions, mitochondrial disease, muscle disorders, or pulmonary disorders, involving administering a PPARδ agonist or a pharmaceutical composition comprising a PPARδ agonist. In one embodiment, the disease or condition is selected from myopathy, inflammatory vascular diseases, Parkinson's and Alzheimer's diseases, systemic inflammatory disorders, renal ischemia, inflammatory rheumatic disorders, and inflammatory diseases of the lung. In another embodiment, methods for increasing oxidative muscle fibers, reducing mitochondria disease, decreasing insulin resistance, decreasing plasma glucose, or decreasing weight, involving administering a PPARδ agonist or a pharmaceutical composition comprising a PPARδ agonist, are provided.

  本文提供了治疗、预防或改善与胰岛素和/或葡萄糖代谢紊乱、炎症性疾病、线粒体病、肌肉疾病或肺部疾病相关的一种或多种症状的方法，其中涉及给予一种PPARδ激动剂或含有PPARδ激动剂的制剂。在一种实施例中，所述疾病或症状被选自肌无力、炎症性血管疾病、帕金森和阿尔茨海默病、全身性炎症性疾病、肾脏缺血、炎症性风湿病和肺部炎症性疾病。在另一种实施例中，提供了通过给予PPARδ激动剂或含有PPARδ激动剂的制剂来增加氧化肌纤维、减少线粒体疾病、降低胰岛素抵抗、降低血浆葡萄糖或减轻体重的方法。
• Activating agent for peroxisome proliferator activated receptor
  申请人：Sakuma Shogo

  公开号：US08648208B2

  公开（公告）日：2014-02-11

  A compound represented by the formula (I) or a pharmacologically acceptable salt thereof is used as an activator of PPAR wherein each of R1 and R2 is hydrogen, C1-8 alkyl, C1-8 alkyl substituted with halogen, or the like; each of R3, R4, R5, and R6 is hydrogen, C1-8 alkyl, or the like; X is sulfur or the like; Y is oxygen, a bond, or the like; p is 0 or 1; A is oxygen, CH2, N—NH2, or the like; when p is 1, B is phenyl, which can have a substituent; when p is 0, B is a condensed ring such as benzisoxazole, which can have a substituent; m is an integer of 1 to 4; and n is an integer of 0 to 5.

  化合物(I)或其药理学上可接受的盐被用作PPAR的激活剂，化合物的表示式为：其中R1和R2中的每一个都是氢、C1-8烷基、C1-8卤代烷基或类似物；R3、R4、R5和R6中的每一个都是氢、C1-8烷基或类似物；X是硫或类似物；Y是氧、键或类似物；p为0或1；A是氧、CH2、N—NH2或类似物；当p为1时，B是苯基，可以有取代基；当p为0时，B是类似苯并异噁唑的融合环，可以有取代基；m是1到4的整数；n是0到5的整数。