3-(3,5-Dimethyl-1,2-oxazol-4-yl)-5-ethoxybenzaldehyde | 1429129-62-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(3,5-Dimethyl-1,2-oxazol-4-yl)-5-ethoxybenzaldehyde
• 英文别名: 3-(3,5-dimethyl-1,2-oxazol-4-yl)-5-ethoxybenzaldehyde
• CAS: 1429129-62-3
• 化学式: C₁₄H₁₅NO₃
• 分子量: 245.278
• InChiKey: PTSHUMZBLIEBTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(3,5-Dimethyl-1,2-oxazol-4-yl)-5-ethoxybenzaldehyde 在 sodium tetrahydroborate 、 三氯氧磷 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 为溶剂， 反应 2.25h， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of GPR40/FFAR1 agonists containing 3,5-dimethylisoxazole

  摘要：

  GPR40 is an attractive target due to its glucose-stimulated insulin secretion effect with low risk of causing hypoglycemia, which also can be seen from the clinical studies using TAK-875 (fasiglifam). In the present studies, we discovered a series of analogues containing 3,5-dimethylisoxazole as potent GPR40 agonists, especially compound ilk with an EC50 value of 15.9 nM. Moreover, compound 11k reduced glucose excursion to 23.1% in ICR mice and 29.5% in type 2 diabetic C57BL/6 mice at 30 mg/kg. It also exhibited satisfactory PK profile. Docking studies were conducted to explain the interaction mode of this series. In summary, compound 11k with robust efficacy in vitro and in vivo is a promising drug candidate for further investigation. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.054
• 作为产物：
  描述：

  3-溴-5-羟基苯甲醛 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 29.0h， 生成 3-(3,5-Dimethyl-1,2-oxazol-4-yl)-5-ethoxybenzaldehyde
  参考文献：
  名称：

  Synthesis and biological evaluation of GPR40/FFAR1 agonists containing 3,5-dimethylisoxazole

  摘要：

  GPR40 is an attractive target due to its glucose-stimulated insulin secretion effect with low risk of causing hypoglycemia, which also can be seen from the clinical studies using TAK-875 (fasiglifam). In the present studies, we discovered a series of analogues containing 3,5-dimethylisoxazole as potent GPR40 agonists, especially compound ilk with an EC50 value of 15.9 nM. Moreover, compound 11k reduced glucose excursion to 23.1% in ICR mice and 29.5% in type 2 diabetic C57BL/6 mice at 30 mg/kg. It also exhibited satisfactory PK profile. Docking studies were conducted to explain the interaction mode of this series. In summary, compound 11k with robust efficacy in vitro and in vivo is a promising drug candidate for further investigation. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.03.054

文献信息

• Optimization of 3,5-Dimethylisoxazole Derivatives as Potent Bromodomain Ligands
  作者：David S. Hewings、Oleg Fedorov、Panagis Filippakopoulos、Sarah Martin、Sarah Picaud、Anthony Tumber、Christopher Wells、Monica M. Olcina、Katherine Freeman、Andrew Gill、Alison J. Ritchie、David W. Sheppard、Angela J. Russell、Ester M. Hammond、Stefan Knapp、Paul E. Brennan、Stuart J. Conway

  DOI：10.1021/jm301588r

  日期：2013.4.25

  The bromodomain protein module, which binds to acetylated lysine, is emerging as an important epigenetic therapeutic target. We report the structure-guided optimization of 3,5-dimethylisoxazole derivatives to develop potent inhibitors of the BET (bromodomain and extra terminal domain) bromodomain family with good ligand efficiency. X-ray crystal structures of the most potent compounds reveal key interactions required for high affinity at BRD4(1). Cellular studies demonstrate that the phenol and acetate derivatives of the lead compounds showed strong antiproliferative effects on MV4;11 acute myeloid leukemia cells, as shown for other BET bromodomain inhibitors and genetic BRD4 knockdown, whereas the reported compounds showed no general cytotoxicity in other cancer cell lines tested.
• Synthesis and biological evaluation of GPR40/FFAR1 agonists containing 3,5-dimethylisoxazole
  作者：Lingyun Yang、Jian Zhang、Lianghui Si、Li Han、Bo Zhang、Hui Ma、Junhao Xing、Leilei Zhao、Jinpei Zhou、Huibin Zhang

  DOI：10.1016/j.ejmech.2016.03.054

  日期：2016.6

  GPR40 is an attractive target due to its glucose-stimulated insulin secretion effect with low risk of causing hypoglycemia, which also can be seen from the clinical studies using TAK-875 (fasiglifam). In the present studies, we discovered a series of analogues containing 3,5-dimethylisoxazole as potent GPR40 agonists, especially compound ilk with an EC50 value of 15.9 nM. Moreover, compound 11k reduced glucose excursion to 23.1% in ICR mice and 29.5% in type 2 diabetic C57BL/6 mice at 30 mg/kg. It also exhibited satisfactory PK profile. Docking studies were conducted to explain the interaction mode of this series. In summary, compound 11k with robust efficacy in vitro and in vivo is a promising drug candidate for further investigation. (C) 2016 Elsevier Masson SAS. All rights reserved.