3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-(piperazin-1-yl)-1H-isochromen-1-one | 1448703-58-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-(piperazin-1-yl)-1H-isochromen-1-one
• 英文别名: 3-(6,8-Dimethylimidazo[1,2-a]pyrazin-2-yl)-7-piperazin-1-ylisochromen-1-one；3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-piperazin-1-ylisochromen-1-one
• CAS: 1448703-58-9
• 化学式: C₂₁H₂₁N₅O₂
• 分子量: 375.43
• InChiKey: IWZCMPUMVWMHLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-(piperazin-1-yl)-1H-isochromen-1-one 、 2-溴乙基甲基醚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以46%的产率得到3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-[4-(2-methoxyethyl)piperazin-1-yl]-1H-isochromen-1-one
  参考文献：
  名称：

  [EN] COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY
  [FR] COMPOSÉS DESTINÉS À TRAITER L'AMYOTROPHIE SPINALE

  摘要：

  本文提供了用于治疗脊髓性肌萎缩症的化合物、其组合物及其用途。

  公开号：

  WO2013112788A1
• 作为产物：
  描述：

  7-fluoro-3-(1-hydroxyethyl)-1H-isochromen-1-one 在 manganese(IV) oxide 、 溴 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 89.0h， 生成 3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-(piperazin-1-yl)-1H-isochromen-1-one
  参考文献：
  名称：

  Discovery and Optimization of Small Molecule Splicing Modifiers of Survival Motor Neuron 2 as a Treatment for Spinal Muscular Atrophy

  摘要：

  The underlying cause of spinal muscular atrophy (SMA) is a deficiency of the survival motor neuron (SMN) protein. Starting from hits identified in a high-throughput screening campaign and through structure activity relationship investigations, we have developed small molecules that potently shift the alternative splicing of the SMN2 exon 7, resulting in increased production of the full-length SMN mRNA and protein. Three novel chemical series, represented by compounds 9, 14, and 20, have been optimized to increase the level of SMN protein by >50% in SMA patient-derived fibroblasts at concentrations of <160 nM. Daily administration of these compounds to severe SMA Delta 7 mice results in an increased production of SMN protein in disease-relevant tissues and a significant increase in median survival time in a dose-dependent manner. Our work supports the development of an orally administered small molecule for the treatment of patients with SMA.

  DOI：

  10.1021/acs.jmedchem.6b00460

文献信息

• COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY
  申请人：PTC Therapeutics, Inc.

  公开号：US20150126515A1

  公开（公告）日：2015-05-07

  Provided herein are compounds, compositions thereof and uses therewith for treating spinal muscular atrophy.

  本文提供了用于治疗脊髓肌肉萎缩症的化合物、其组合物和使用方法。
• US9399649B2
  申请人：——

  公开号：US9399649B2

  公开（公告）日：2016-07-26
• [EN] METHODS FOR MODULATING THE AMOUNT OF RNA TRANSCRIPTS<br/>[FR] PROCÉDÉS POUR LA MODULATION DE LA QUANTITÉ DE PRODUITS DE LA TRANSCRIPTION D'ARN
  申请人：PTC THERAPEUTICS INC

  公开号：WO2015095446A1

  公开（公告）日：2015-06-25

  Described herein are methods for modulating the amount of a gene product and compounds for use in such methods. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product as the result of gene expression and compounds for use in such methods.