2,8-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a] pyridine | 1947395-70-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 2,8-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a] pyridine
• 英文别名: 2,8-Dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine
• CAS: 1947395-70-1
• 化学式: C₁₅H₂₁BN₂O₂
• 分子量: 272.155
• InChiKey: LJVWHIRQMKGXQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.25
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  35.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2,8-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a] pyridine 、 6-bromo-2-(1-methylpiperidin-4-yl)-3H-quinazolin-4-one 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 水 、 乙腈 为溶剂， 以40 mg的产率得到6-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(1-methylpiperidin-4-yl)-3H-quinazolin-4-one
  参考文献：
  名称：

  Substituted pyrazolo[1,5-a]pyrazines for spinal muscular atrophy

  摘要：

  A prophylactic or therapeutic agent for spinal muscular atrophy according to the present invention includes a compound represented by the formula (I) or a salt thereof: the variables are described herein.

  公开号：

  US12012410B2
• 作为产物：
  描述：

  2-氨基-3-甲基-5-溴吡啶 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2,8-dimethyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a] pyridine
  参考文献：
  名称：

  [EN] IMIDAZO[1,2-A]PYRIDINE COMPOUNDS FOR THE TREATMENT OF AUTOIMMUNE DISEASE
  [FR] COMPOSÉS IMIDAZO[1,2-A]PYRIDINE POUR LE TRAITEMENT D'UNE MALADIE AUTO-IMMUNE

  摘要：

  本发明涉及式(I)的化合物，其中R1、R2、R3、R4、R5和A如本文所述，以及其药学上可接受的盐，以及包括该化合物的组合物和使用该化合物的方法。

  公开号：

  WO2022029069A1

文献信息

• 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.
• Discovery and Optimization of Small Molecule Splicing Modifiers of Survival Motor Neuron 2 as a Treatment for Spinal Muscular Atrophy
  作者：Matthew G. Woll、Hongyan Qi、Anthony Turpoff、Nanjing Zhang、Xiaoyan Zhang、Guangming Chen、Chunshi Li、Song Huang、Tianle Yang、Young-Choon Moon、Chang-Sun Lee、Soongyu Choi、Neil G. Almstead、Nikolai A. Naryshkin、Amal Dakka、Jana Narasimhan、Vijayalakshmi Gabbeta、Ellen Welch、Xin Zhao、Nicole Risher、Josephine Sheedy、Marla Weetall、Gary M. Karp

  DOI：10.1021/acs.jmedchem.6b00460

  日期：2016.7.14

  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.