3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one | 1453265-64-9

• 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-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one
• 英文别名: 3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-[(3S)-3-methylpiperazin-1-yl]pyrano[2,3-b]pyridin-2-one
• CAS: 1453265-64-9
• 化学式: C₂₁H₂₂N₆O₂
• 分子量: 390.445
• InChiKey: YOTNTOHMVROYOB-LBPRGKRZSA-N

物化性质

• 密度：
  1.44±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  6-氯吡啶-2-醇 在 哌啶 、 溶剂黄146 、 三乙胺 、 三氟乙酸 、 magnesium chloride 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 、 正丁醇 为溶剂， 反应 51.0h， 生成 3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one
  参考文献：
  名称：

  Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy

  摘要：

  Spinal muscular atrophy (SMA) is the leading genetic cause of infant and toddler mortality, and there is currently no approved therapy available. SMA is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. These mutations or deletions result in low levels of functional SMN protein. SMN2, a paralogous gene to SMN1, undergoes alternative splicing and exclusion of exon 7, producing an unstable, truncated SMI\T07 protein. Herein, we report the identification of a pyridopyrimidinone series of small molecules that modify the alternative splicing of SMN2, increasing the production of fulllength SMN2 mRNA. Upon oral administration of our small molecules, the levels of fulllength SMN protein were restored in two mouse models of SMA. In-depth lead optimization in the pyridopyrimidinone series culminated in the selection of compound 3 (RG7800), the first small molecule SMN2 splicing modifier to enter human clinical trials.

  DOI：

  10.1021/acs.jmedchem.6b00459

文献信息

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

  公开号：US20150166575A1

  公开（公告）日：2015-06-18

  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、其组合物及其使用方法。
• US9371336B2
  申请人：——

  公开号：US9371336B2

  公开（公告）日：2016-06-21