1-(3-(3,5-dimethylisoxazol-4-yl)phenyl)ethanone | 1188281-21-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-(3,5-dimethylisoxazol-4-yl)phenyl)ethanone
• 英文别名: 1-3-(3,5-dimethylisoxazol-4-yl)phenylethanone；3-(3,5-dimethylisoxazol-4-yl)acetophenone；1-[3-(3,5-Dimethyl-1,2-oxazol-4-yl)phenyl]ethanone
• CAS: 1188281-21-1
• 化学式: C₁₃H₁₃NO₂
• 分子量: 215.252
• InChiKey: PQDJCPDVQWLFCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-(3,5-dimethylisoxazol-4-yl)phenyl)ethanone 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以77%的产率得到(RS)-1-(3-(3,5-dimethylisoxazol-4-yl)phenyl)ethanol
  参考文献：
  名称：

  3,5-Dimethylisoxazoles Act As Acetyl-lysine-mimetic Bromodomain Ligands

  摘要：

  Histone-lysine acetylation is a vital chromatin post-translational modification involved in the epigenetic regulation of gene transcription. Bromodomains bind acetylated lysines, acting as readers of the histone-acetylation code. Competitive inhibitors of this interaction have antiproliferative and anti-inflammatory properties. With 57 distinct bromodomains known, the discovery of subtype-selective inhibitors of the histone bromodomain interaction is of great importance. We have identified the 3,5-dimethylisoxazole moiety as a novel acetyl-lysine bioisostere, which displaces acetylated histone-mimicking peptides from bromodomains. Using X-ray crystallographic analysis, we have determined the interactions responsible for the activity and selectivity of 4-substituted 3,5-dimethylisoxazoles against a selection of phylogenetically diverse bromodomains. By exploiting these interactions, we have developed compound 4d, which has IC50 values of < 5 mu M for the bromodomain-containing proteins BRD2(1) and BRD4(1). These compounds are promising leads for the further development of selective probes for the bromodomain and extra C-terminal domain (BET) family and CREBBP bromodomains.

  DOI：

  10.1021/jm200640v
• 作为产物：
  描述：

  3,5-二甲基异恶唑-4-硼酸 在 potassium hydrogen difluoride 、 palladium diacetate 、 sodium carbonate 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 13.17h， 生成 1-(3-(3,5-dimethylisoxazol-4-yl)phenyl)ethanone
  参考文献：
  名称：

  3,5-Dimethylisoxazoles Act As Acetyl-lysine-mimetic Bromodomain Ligands

  摘要：

  Histone-lysine acetylation is a vital chromatin post-translational modification involved in the epigenetic regulation of gene transcription. Bromodomains bind acetylated lysines, acting as readers of the histone-acetylation code. Competitive inhibitors of this interaction have antiproliferative and anti-inflammatory properties. With 57 distinct bromodomains known, the discovery of subtype-selective inhibitors of the histone bromodomain interaction is of great importance. We have identified the 3,5-dimethylisoxazole moiety as a novel acetyl-lysine bioisostere, which displaces acetylated histone-mimicking peptides from bromodomains. Using X-ray crystallographic analysis, we have determined the interactions responsible for the activity and selectivity of 4-substituted 3,5-dimethylisoxazoles against a selection of phylogenetically diverse bromodomains. By exploiting these interactions, we have developed compound 4d, which has IC50 values of < 5 mu M for the bromodomain-containing proteins BRD2(1) and BRD4(1). These compounds are promising leads for the further development of selective probes for the bromodomain and extra C-terminal domain (BET) family and CREBBP bromodomains.

  DOI：

  10.1021/jm200640v

文献信息

• Ligand-Free-Palladium-Catalyzed Direct 4-Arylation of Isoxazoles Using Aryl Bromides
  作者：Yacoub Fall、Céline Reynaud、Henri Doucet、Maurice Santelli

  DOI：10.1002/ejoc.200900309

  日期：2009.8

  palladium-catalysed C–H bond activation/arylation of 3,5-disubstituted isoxazoles using aryl or heteroaryl bromides. Good yields were generally obtained by using 0.1–0.5 mol-% of the air-stable PdCl2 complex as the catalyst. A range of functional groups such as acetyl, formyl, ester, fluoro, nitro, trifluoromethyl or nitrile on the aryl bromide is tolerated. This reaction is environmentally attractive, as the

  4-芳基异恶唑可以很容易地通过钯催化的 C-H 键活化/使用芳基或杂芳基溴化物对 3,5-二取代异恶唑进行芳基化来制备。通常使用 0.1-0.5 mol% 的空气稳定 PdCl2 配合物作为催化剂可以获得良好的产率。允许芳基溴上的一系列官能团，例如乙酰基、甲酰基、酯、氟、硝基、三氟甲基或腈。该反应对环境具有吸引力，因为主要废物是 KBr/AcOH，而不是传统交叉偶联过程中产生的金属盐。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
• 3,5-Dimethylisoxazoles Act As Acetyl-lysine-mimetic Bromodomain Ligands
  作者：David S. Hewings、Minghua Wang、Martin Philpott、Oleg Fedorov、Sagar Uttarkar、Panagis Filippakopoulos、Sarah Picaud、Chaitanya Vuppusetty、Brian Marsden、Stefan Knapp、Stuart J. Conway、Tom D. Heightman

  DOI：10.1021/jm200640v

  日期：2011.10.13

  Histone-lysine acetylation is a vital chromatin post-translational modification involved in the epigenetic regulation of gene transcription. Bromodomains bind acetylated lysines, acting as readers of the histone-acetylation code. Competitive inhibitors of this interaction have antiproliferative and anti-inflammatory properties. With 57 distinct bromodomains known, the discovery of subtype-selective inhibitors of the histone bromodomain interaction is of great importance. We have identified the 3,5-dimethylisoxazole moiety as a novel acetyl-lysine bioisostere, which displaces acetylated histone-mimicking peptides from bromodomains. Using X-ray crystallographic analysis, we have determined the interactions responsible for the activity and selectivity of 4-substituted 3,5-dimethylisoxazoles against a selection of phylogenetically diverse bromodomains. By exploiting these interactions, we have developed compound 4d, which has IC50 values of < 5 mu M for the bromodomain-containing proteins BRD2(1) and BRD4(1). These compounds are promising leads for the further development of selective probes for the bromodomain and extra C-terminal domain (BET) family and CREBBP bromodomains.