4-(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzene-1,2-diamine | 1137671-57-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzene-1,2-diamine
• 英文别名: 4-[5-(4-Methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-benzene-1,2-diamine；4-[5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl]benzene-1,2-diamine
• CAS: 1137671-57-8
• 化学式: C₁₅H₁₄N₄O₂
• 分子量: 282.302
• InChiKey: RENGNJUAFMBRDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzene-1,2-diamine 在 5%-palladium/activated carbon 、 oxone 、 氢气 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 5.33h， 生成 3-(4-(6-(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)-1H-benzo[d]imidazol-2-yl)-3,5-dimethylphenyl)propanoic acid
  参考文献：
  名称：

  Discovery of an Orally Bioavailable Benzimidazole Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitor That Suppresses Body Weight Gain in Diet-Induced Obese Dogs and Postprandial Triglycerides in Humans

  摘要：

  Modification of a gut restricted class of benziMidazole DGAT1 inhibitor 1 led to 9 with good oral bioavailability. The key structural changes to 1 include bioisosteric replacement of the amide with oxadiazole and a,a-dimethylation of the carboxylic acid, improving DGAT1 potency and gut permeability. Since DGAT1 is expressed in the small intestine, both 1,and 9 can suppress postprandial triglycerides during acute oral lipid challenges in rats and dogs. Interestingly, only 9 was found to be effective in suppressing body weight gain relative to control in a diet-induced obese dog model, suggesting the importance of systemic inhibition of DGAT1 for body weight control. 9 has advanced to clinical investigation and successfully suppr8sed postprandial triglycerides during an acute meal challenge in humans.

  DOI：

  10.1021/acs.jmedchem.7b00173
• 作为产物：
  描述：

  4-氨基-3-硝基苯甲酸 在 platinum(IV) oxide 、 伯吉斯试剂 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0~150.0 ℃ 、101.33 kPa 条件下， 反应 75.5h， 生成 4-(5-(4-methoxyphenyl)-1,3,4-oxadiazol-2-yl)benzene-1,2-diamine
  参考文献：
  名称：

  Discovery of an Orally Bioavailable Benzimidazole Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitor That Suppresses Body Weight Gain in Diet-Induced Obese Dogs and Postprandial Triglycerides in Humans

  摘要：

  Modification of a gut restricted class of benziMidazole DGAT1 inhibitor 1 led to 9 with good oral bioavailability. The key structural changes to 1 include bioisosteric replacement of the amide with oxadiazole and a,a-dimethylation of the carboxylic acid, improving DGAT1 potency and gut permeability. Since DGAT1 is expressed in the small intestine, both 1,and 9 can suppress postprandial triglycerides during acute oral lipid challenges in rats and dogs. Interestingly, only 9 was found to be effective in suppressing body weight gain relative to control in a diet-induced obese dog model, suggesting the importance of systemic inhibition of DGAT1 for body weight control. 9 has advanced to clinical investigation and successfully suppr8sed postprandial triglycerides during an acute meal challenge in humans.

  DOI：

  10.1021/acs.jmedchem.7b00173

文献信息

• [EN] OXADIAZOLE- AND OXAZOLE-SUBSTITUTED BENZIMIDAZOLE- AND INDOLE-DERIVATIVES AS DGAT1 INHIBITORS<br/>[FR] DÉRIVÉS DE BENZIMIDAZOLE ET D'INDOLE SUBSTITUÉS PAR DE L'OXADIAZOLE ET OXAZOLE COMME INHIBITEURS DE DGAT1
  申请人：NOVARTIS AG

  公开号：WO2009040410A1

  公开（公告）日：2009-04-02

  The present invention provides oxadiazolyl- substituted benzimidazole- and idole-derivates that are useful for treating conditions or disorders associated with DGAT1 activity in animals, particularly humans.

  本发明提供了一种对氧代二唑基取代的苯并咪唑和吲哚衍生物，用于治疗与动物，特别是人类的DGAT1活性相关的疾病或疾病。
• ORGANIC COMPOUNDS
  申请人：Kwak Young-Shin

  公开号：US20110077277A1

  公开（公告）日：2011-03-31

  The present invention provides compounds of the following structure; A-Q-B—C-D that are useful for treating conditions or disorders associated with DGAT1 activity in animals, particularly humans.

  本发明提供了以下结构的化合物; A-Q-B-C-D，用于治疗与动物（尤其是人类）中的DGAT1活性相关的病症或疾病。
• Organic compounds
  申请人：Novartis AG

  公开号：US07879850B2

  公开（公告）日：2011-02-01

  The present invention provides compounds of the following structure; A-Q-B—C-D that are useful for treating conditions or disorders associated with DGAT1 activity in animals, particularly humans.

  本发明提供以下结构的化合物; A-Q-B-C-D，它们对于治疗与动物中DGAT1活性相关的疾病或疾病特别是人类非常有用。
• OXADIAZOLE- AND OXAZOLE-SUBSTITUTED BENZIMIDAZOLE- AND INDOLE-DERIVATIVES AS DGAT1 INHIBITORS
  申请人：Novartis AG

  公开号：EP2205595A1

  公开（公告）日：2010-07-14
• US7879850B2
  申请人：——

  公开号：US7879850B2

  公开（公告）日：2011-02-01