7-fluoro-2-(2-methylimidazo [1,2-a]pyridin-6-yl)-4H-pyrido[1,2-a]pyrimidin-4-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 7-fluoro-2-(2-methylimidazo [1,2-a]pyridin-6-yl)-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 7-fluoro-2-(2-methylimidazo[1,2-a]pyridin-6-yl)pyrido[1,2-a]pyrimidin-4-one；7-fluoro-2-(2-methylimidazo[1,2-a]pyridin-6-yl)-4H-pyrido[1,2-a]pyrimidin-4-one
• 化学式: C₁₆H₁₁FN₄O
• 分子量: 294.288
• InChiKey: SANDDEAYUVXDAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  50
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  哌嗪 、 7-fluoro-2-(2-methylimidazo [1,2-a]pyridin-6-yl)-4H-pyrido[1,2-a]pyrimidin-4-one 以 N,N-二甲基乙酰胺 为溶剂， 反应 1.0h， 以61%的产率得到2-(2-methylimidazo[1,2-a]pyridin-6-yl)-7-(piperazin-1-yl)-4H-pyrido [1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  [EN] COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY
  [FR] COMPOSÉS DESTINÉS AU TRAITEMENT DE L'AMYOTROPHIE SPINALE

  摘要：

  公开号：

  WO2013119916A3
• 作为产物：
  描述：

  2-氨基-5-氟吡啶 在 四(三苯基膦)钯 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 水 、 乙腈 为溶剂， 反应 23.5h， 生成 7-fluoro-2-(2-methylimidazo [1,2-a]pyridin-6-yl)-4H-pyrido[1,2-a]pyrimidin-4-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：US20180105526A1

  公开（公告）日：2018-04-19

  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性肌萎缩症的化合物、其组成物和使用方法。
• Compounds for treating spinal muscular atrophy
  申请人：PTC Therapeutics, Inc.

  公开号：US10851101B2

  公开（公告）日：2020-12-01

  Provided herein are compounds of Formula (I): and forms thereof, including compositions thereof and uses therewith for treating spinal muscular atrophy.

  本文提供的是式 (I) 化合物： 及其形式，包括其组合物和用途，用于治疗脊髓性肌萎缩症。
• US9586955B2
  申请人：——

  公开号：US9586955B2

  公开（公告）日：2017-03-07
• US9879007B2
  申请人：——

  公开号：US9879007B2

  公开（公告）日：2018-01-30
• Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine To Treat Spinal Muscular Atrophy
  作者：Hasane Ratni、Gary M. Karp、Marla Weetall、Nikolai A. Naryshkin、Sergey V. Paushkin、Karen S. Chen、Kathleen D. McCarthy、Hongyan Qi、Anthony Turpoff、Matthew G. Woll、Xiaoyan Zhang、Nanjing Zhang、Tianle Yang、Amal Dakka、Priya Vazirani、Xin Zhao、Emmanuel Pinard、Luke Green、Pascale David-Pierson、Dietrich Tuerck、Agnes Poirier、Wolfgang Muster、Stephan Kirchner、Lutz Mueller、Irene Gerlach、Friedrich Metzger

  DOI：10.1021/acs.jmedchem.6b00459

  日期：2016.7.14

  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.