3-(4-formyl-3,5-dimethylphenyl)acrylic acid methyl ester | 1021166-62-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 3-(4-formyl-3,5-dimethylphenyl)acrylic acid methyl ester
• 英文别名: 3-(4-Formyl-3,5-dimethylphenyl)-acrylic acid methyl ester；methyl 3-(4-formyl-3,5-dimethylphenyl)prop-2-enoate
• CAS: 1021166-62-0
• 化学式: C₁₃H₁₄O₃
• 分子量: 218.252
• InChiKey: GXOHOVHIYHGUKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-formyl-3,5-dimethylphenyl)acrylic acid methyl ester 在 钯 二氯甲烷 、 ethyl acetate heptane 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 3-(4-formyl-3,5-dimethylphenyl)propionic acid methyl ester
  参考文献：
  名称：

  ORGANIC COMPOUNDS

  摘要：

  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。

  公开号：

  US20110077277A1
• 作为产物：
  描述：

  2,2,2-trifluoro-N-(4-formyl-3,5-dimethylphenyl)acetamide 在 tetrafluoroboric acid 、 sodium hydroxide 、 sodium nitrite 作用下， 以 甲醇 、 水 为溶剂， 反应 19.0h， 生成 3-(4-formyl-3,5-dimethylphenyl)acrylic acid methyl ester
  参考文献：
  名称：

  Intestinally Targeted Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitors Robustly Suppress Postprandial Triglycerides

  摘要：

  High DGAT1 expression levels in the small intestine highlight the critical role this enzyme plays in nutrient absorption. Identification of inhibitors which predominantly inhibit DGAT1 in the gut is an attractive drug discovery strategy with anticipated benefits of reduced systemic toxicity. In this report we describe our discovery and optimization of DGAT1 inhibitors whose plasma exposure is minimized by the action of transporters, including the P-glycoprotein transporter. The impact of this unique absorption profile on efficacy in rat and dog efficacy models is presented.

  DOI：

  10.1021/ml3000512

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。
• 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
  作者：Katsumasa Nakajima、Ricardo Chatelain、Kevin B. Clairmont、Renee Commerford、Gary M. Coppola、Thomas Daniels、Cornelia J. Forster、Thomas A. Gilmore、Yongjin Gong、Monish Jain、Aaron Kanter、Youngshin Kwak、Jingzhou Li、Charles D. Meyers、Alan D. Neubert、Paul Szklennik、Vivienne Tedesco、James Thompson、David Truong、Qing Yang、Brian K. Hubbard、Michael H. Serrano-Wu

  DOI：10.1021/acs.jmedchem.7b00173

  日期：2017.6.8

  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.
• Intestinally Targeted Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitors Robustly Suppress Postprandial Triglycerides
  作者：Michael H. Serrano-Wu、Gary M. Coppola、Yongjin Gong、Alan D. Neubert、Ricardo Chatelain、Kevin B. Clairmont、Renee Commerford、Theresa Cosker、Thomas Daniels、Ying Hou、Monish Jain、Marlene Juedes、Lisha Li、Tara Mullarkey、Erik Rocheford、Moo Je Sung、Andrew Tyler、Qing Yang、Taeyoung Yoon、Brian K. Hubbard

  DOI：10.1021/ml3000512

  日期：2012.5.10

  High DGAT1 expression levels in the small intestine highlight the critical role this enzyme plays in nutrient absorption. Identification of inhibitors which predominantly inhibit DGAT1 in the gut is an attractive drug discovery strategy with anticipated benefits of reduced systemic toxicity. In this report we describe our discovery and optimization of DGAT1 inhibitors whose plasma exposure is minimized by the action of transporters, including the P-glycoprotein transporter. The impact of this unique absorption profile on efficacy in rat and dog efficacy models is presented.