N-(3-acetylphenyl)-3-chloropropanamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(3-acetylphenyl)-3-chloropropanamide
• 英文别名: N-(3-acetylphenyl)-3-chloro-propanamide
• 化学式: C₁₁H₁₂ClNO₂
• 分子量: 225.675
• InChiKey: SQLSVXHFIHHZDH-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：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  四氢异喹啉 、 N-(3-acetylphenyl)-3-chloropropanamide 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 0.17h， 以65%的产率得到N-(3-acetylphenyl)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propanamide
  参考文献：
  名称：

  Discovery of new potent protein arginine methyltransferase 5 (PRMT5) inhibitors by assembly of key pharmacophores from known inhibitors

  摘要：

  Protein arginine methyltransferase 5 (PRMT5) is an epigenetics related enzyme that has been validated as a promising therapeutic target for human cancer. Up to now, two small molecule PRMT5 inhibitors has been put into phase I clinical trial. In the present study, a series of candidate molecules were designed by combining key pharmacophores of formerly reported PRMT5 inhibitors. The in vitro PRMT5 inhibitory testing of compound 4b14 revealed an IC50 of 2.71 mu M, exhibiting high selectivity over PRMT1 and PRMT4 (> 70-fold selective). As expected, 4b14 exhibited potent anti-proliferative activity against a panel of leukemia and lymphoma cells, including MV4-11, Pfeiffer, SU-DHL-4 and KARPAS-422. Besides, 4b14 showed significant cell cycle arrest and apoptosis-inducing effects, as well as reduced the cellular symmetric arginine dimethylation level of SmD3 protein. Finally, affinity profiling analysis indicated that hydrophobic interactions, pi-pi stacking and cation-pi actions made the major contributions to the overall binding affinity. This scaffold provides a new chemical template for further development of better lead compounds targeting PRMT5.

  DOI：

  10.1016/j.bmcl.2018.10.026
• 作为产物：
  描述：

  间氨基苯乙酮 、 3-氯丙酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以71%的产率得到N-(3-acetylphenyl)-3-chloropropanamide
  参考文献：
  名称：

  Discovery of new potent protein arginine methyltransferase 5 (PRMT5) inhibitors by assembly of key pharmacophores from known inhibitors

  摘要：

  Protein arginine methyltransferase 5 (PRMT5) is an epigenetics related enzyme that has been validated as a promising therapeutic target for human cancer. Up to now, two small molecule PRMT5 inhibitors has been put into phase I clinical trial. In the present study, a series of candidate molecules were designed by combining key pharmacophores of formerly reported PRMT5 inhibitors. The in vitro PRMT5 inhibitory testing of compound 4b14 revealed an IC50 of 2.71 mu M, exhibiting high selectivity over PRMT1 and PRMT4 (> 70-fold selective). As expected, 4b14 exhibited potent anti-proliferative activity against a panel of leukemia and lymphoma cells, including MV4-11, Pfeiffer, SU-DHL-4 and KARPAS-422. Besides, 4b14 showed significant cell cycle arrest and apoptosis-inducing effects, as well as reduced the cellular symmetric arginine dimethylation level of SmD3 protein. Finally, affinity profiling analysis indicated that hydrophobic interactions, pi-pi stacking and cation-pi actions made the major contributions to the overall binding affinity. This scaffold provides a new chemical template for further development of better lead compounds targeting PRMT5.

  DOI：

  10.1016/j.bmcl.2018.10.026

文献信息

• Lithographic Printing Plate Precursor
  申请人：Loccufier Johan

  公开号：US20120266768A1

  公开（公告）日：2012-10-25

  A positive-working lithographic printing plate precursor is disclosed which comprises on a support having a hydrophilic surface or which is provided with a hydrophilic layer a heat and/or light-sensitive coating including an infrared absorbing agent, said heat and/or light-sensitive coating comprising a first layer comprising a binder including a monomeric unit including a sulfonamide group; characterized in that the binder further comprises a monomeric unit including a phosphonic acid group or a salt thereof, and that the monomeric unit comprising the phosphonic acid group is present in an amount comprised between 2 mol % and 15 mol %.

  本发明公开了一种阳性印刷版前体，其包括在具有亲水表面的支撑体上或在其上提供了亲水层的支撑体上，包括红外吸收剂的热和/或光敏涂层，所述热和/或光敏涂层包括第一层，其中包括一种包括磺酰胺基的单体单元的粘合剂；其特征在于，所述粘合剂进一步包括一种包括膦酸基或其盐的单体单元，并且含有膦酸基的单体单元的量在2摩尔％至15摩尔％之间。