2,2,6,6-tetramethyl-4-methylenepiperidine trifluoroacetate | 137003-50-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2,2,6,6-tetramethyl-4-methylenepiperidine trifluoroacetate
• 英文别名: 2,2,6,6-Tetramethyl-4-methylenepiperidine trifluoroacetate；2,2,6,6-tetramethyl-4-methylidenepiperidine;2,2,2-trifluoroacetic acid
• CAS: 137003-50-0
• 化学式: C₂HF₃O₂*C₁₀H₁₉N
• 分子量: 267.292
• InChiKey: ONASENZNGCCTQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.12
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,2,6,6-tetramethyl-4-methylenepiperidine trifluoroacetate 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 、 三乙胺 、 9-硼双环[3.3.1]壬烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 39.0h， 生成 3-methoxy-4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-yl)phenyl trifluoromethanesulfonate
  参考文献：
  名称：

  Discovery of Small Molecule Splicing Modulators of Survival Motor Neuron-2 (SMN2) for the Treatment of Spinal Muscular Atrophy (SMA)

  摘要：

  Spinal muscular atrophy (SMA), a rare neuromuscular disorder, is the leading genetic cause of death in infants and toddlers. SMA is caused by the deletion or a loss of function mutation of the survival motor neuron 1 (SMN1) gene. In humans, a second closely related gene SMN2 exists; however it codes for a less stable SMN protein. In recent years, significant progress has been made toward disease modifying treatments for SMA by modulating SMN2 pre-mRNA splicing. Herein, we describe the discovery of LMI070/branaplam, a small molecule that stabilizes the interaction between the spliceosome and SMN2 pre-mRNA. Branaplam (1) originated from a high-throughput phenotypic screening hit, pyridazine 2, and evolved via multiparameter lead optimization. In a severe mouse SMA model, branaplam treatment increased full-length SMN RNA and protein levels, and extended survival. Currently, branaplam is in clinical studies for SMA.

  DOI：

  10.1021/acs.jmedchem.8b01291
• 作为产物：
  描述：

  四甲基哌啶酮 、 甲基三苯基溴化膦 、 三氟乙酸 以 乙醚 为溶剂， 反应 0.5h， 以70%的产率得到2,2,6,6-tetramethyl-4-methylenepiperidine trifluoroacetate
  参考文献：
  名称：

  [EN] 1,4-DISUBSTITUTED PYRIDAZINE ANALOGS AND METHODS FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS
  [FR] ANALOGUES DE PYRIDAZINE 1,4-DISUBSTITUÉE ET PROCÉDÉS DE TRAITEMENT DE TROUBLES LIÉS À UNE DÉFICIENCE EN SMN

  摘要：

  本发明提供了一种公式(I)的化合物或其药用可接受的盐；一种制造本发明化合物的方法及其治疗用途。本发明进一步提供了一种药物活性剂的组合物和一种药物组合物。

  公开号：

  WO2014028459A1

文献信息

• 1,4-DISUBSTITUTED PYRIDAZINE ANALOGS THERE OF AND METHODS FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS
  申请人：NOVARTIS AG

  公开号：US20170290828A1

  公开（公告）日：2017-10-12

  The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了式I的化合物或其药学上可接受的盐；制备本发明化合物的方法以及其治疗用途。本发明还提供了具有药理活性剂的组合物和制药组合物。
• 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions
  申请人：Cheung Atwood Kim

  公开号：US08729263B2

  公开（公告）日：2014-05-20

  The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了公式I的化合物或其药学上可接受的盐；一种制造该发明化合物的方法以及其治疗用途。本发明还提供了一种药理活性剂的组合和制药组合物。
• 1,4-disubstituted pyridazine analogs thereof and methods for treating SMN-deficiency-related conditions
  申请人：Novartis AG

  公开号：US11229648B2

  公开（公告）日：2022-01-25

  The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种式 I 的化合物或其药学上可接受的盐； 一种制造本发明化合物的方法及其治疗用途。本发明还提供了一种药理活性剂组合和药物组合物。
• Mixed aggregation of lithium enolates and lithium halides with lithium 2,2,6,6-tetramethylpiperidide (LiTMP)
  作者：Patricia L. Hall、James H. Gilchrist、Aidan T. Harrison、David J. Fuller、David B. Collum

  DOI：10.1021/ja00025a024

  日期：1991.12

  Li-6 and N-15 NMR spectroscopic studies of [Li-6]-LiTMP and [Li-6,N-15]-LiTMP support an earlier suggestion that LiTMP exists as a dimer-monomer mixture in THF. In the presence of [Li-6]-lithium cyclohexenolate as a representative enolate, one observes mixed aggregates with 2:1, 1:1, and 2:2 LiTMP/enolate stoichiometries. Evidence of conformational isomerism is observed in the slow-exchange limit. Studies of conformationally mobile [Li-6]-lithium di-tert-butylamide and conformationally locked [Li-6]-lithium 2,2,4,6,6-pentamethylpiperidide shed further light on the spectroscopic consequences of the chair form of the piperidine ring system. The corresponding studies of LiTMP/LiBr mixtures reveal the predominance of a 1:1 mixed aggregate, a lower propensity to form 2:1 mixed aggregates than the analogous lithium enolate case, and no tendency whatsoever to form 2:2 mixed aggregates. LiTMP/LiCl mixtures appear to contain two conformational isomers of the 2:1 stoichiometry analogous to the LiTMP enolate case as well as a 1:1 mixed aggregate in the limit of high LiCl concentration. Severe spectral overlaps and several unassigned resonances render the LiTMP-LiCl mixed aggregate structure assignments the most tentative.
• 1,4-DISUBSTITUTED PYRIDAZINE ANALOGS AND METHODS FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS
  申请人：Novartis AG

  公开号：EP2885288A1

  公开（公告）日：2015-06-24