8-fluoro-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine | 1449599-86-3

• 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: 8-fluoro-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine
• CAS: 1449599-86-3
• 化学式: C₁₄H₁₈BFN₂O₂
• 分子量: 276.119
• InChiKey: KGGZBUVODWJXGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.08
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  35.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-fluoro-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 8.0h， 生成 tert-butyl 4-(2-{8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl}-4-(methylcarbamoyl)quinazolin-6-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  [EN] 2-(INDAZOL-5-YL)-6-(PIPERIDIN-4-YL)-1,7-NAPHTHYRIDINE DERIVATIVES AND RELATED COMPOUNDS AS MODULATORS FOR SPLICING NUCLEIC ACIDS AND FOR THE TREATMENT OF PROLIFERATIVE DISEASES
  [FR] DÉRIVÉS DE 2-(INDAZOL-5-YL)-6-(PIPÉRIDIN-4-YL)-1,7-NAPHTYRIDINE ET COMPOSÉS ASSOCIÉS UTILES COMME MODULATEURS POUR L'ÉPISSAGE D'ACIDES NUCLÉIQUES ET POUR LE TRAITEMENT DE MALADIES PROLIFÉRATIVES

  摘要：

  The present disclosure features compounds and related compositions that, inter alia, modulate nucleic acid splicing, e.g., splicing of a pre-mRNA, as well as methods of use thereof.

  公开号：

  WO2023133217A1
• 作为产物：
  描述：

  2-氨基-5-溴-3-氟吡啶 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium acetate 、 4-甲基苯磺酸吡啶 作用下， 以 1,4-二氧六环 、 异丙醇 为溶剂， 反应 5.0h， 生成 8-fluoro-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2-a]pyridine
  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

• [EN] FUSED BICYCLIC COMPOUNDS USEFUL FOR MODULATING NUCLEIC ACID SPLICING<br/>[FR] COMPOSÉS BICYCLIQUES FUSIONNÉS UTILES POUR MODULER L'ÉPISSAGE D'ACIDE NUCLÉIQUE
  申请人：REMIX THERAPEUTICS INC

  公开号：WO2021174163A1

  公开（公告）日：2021-09-02

  The present disclosure features compounds and related compositions that, inter alia, modulate nucleic acid splicing, e.g., splicing of a pre-mRNA, as well as methods of use thereof.

  本公开涉及化合物和相关组合物，其中包括调节核酸剪接，例如预mRNA的剪接，以及其使用方法。
• COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY
  申请人：PTC Therapeutics Inc.

  公开号：US20150005289A1

  公开（公告）日：2015-01-01

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

  本文提供了化合物、其组合物以及与其一起治疗脊髓肌肉萎缩症的用途。
• [EN] COMPOUNDS FOR TREATING HUNTINGTON'S DISEASE<br/>[FR] COMPOSÉS PERMETTANT DE TRAITER LA MALADIE DE HUNTINGTON
  申请人：PTC THERAPEUTICS INC

  公开号：WO2018226622A8

  公开（公告）日：2020-01-16
• [EN] COMPOUNDS AND METHODS FOR MODULATING SPLICING<br/>[FR] COMPOSÉS ET PROCÉDÉS DE MODULATION DE L'ÉPISSAGE
  申请人：REMIX THERAPEUTICS INC

  公开号：WO2021207530A8

  公开（公告）日：2021-12-02
• Identification and Optimization of RNA-Splicing Modulators as Huntingtin Protein-Lowering Agents for the Treatment of Huntington’s Disease
  作者：Longbin Liu、Karine Malagu、Alan F. Haughan、Vinod Khetarpal、Andrew J. Stott、William Esmieu、Huw D. Vater、Stephen J. Webster、Amanda J. Van de Poël、Cole Clissold、Brett Cosgrove、Benjamin Sutton、Jonathan A. Spencer、Perla Breccia、Emanuela Gancia、Silvia Bonomo、Tammy Ladduwahetty、Ovadia Lazari、Hiral Patel、Helen C. Atton、Steve Clifton、Daniel M. Mota、Dario Magnani、Amy O’Neill、Marta Stebbeds、Natsuko Macabuag、Daniel Todd、Maria E. Herva、Philip Mitchell、Mijke Visser、Sara Compte Sancerni、Laure Grand Moursel、Marta da Silva、Eva Kritikou、Taneli T. Heikkinen、Tamuna Bolkvadze、Valentina Fodale、Debora Spadafora、Manuel Daldin、Alberto Bresciani、John E. Mangette、Elizabeth M. Doherty、Matthew R. Lee、Todd Herbst、Edith Monteagudo、Douglas Macdonald、Nikolay V. Plotnikov、Mark Chambers、George McAllister、Ignacio Muňoz-Sanjuan、Celia Dominguez

  DOI：10.1021/acs.jmedchem.3c01173

  日期：2023.9.28