5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-yl)phenol | 1562337-07-8

• 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: 5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-yl)phenol
• 英文别名: 5-(1H-Pyrazol-4-yl)-2-[6-[(2,2,6,6-tetramethyl-4-piperidinyl)methyl]-3-pyridazinyl]phenol；5-(1H-pyrazol-4-yl)-2-[6-[(2,2,6,6-tetramethylpiperidin-4-yl)methyl]pyridazin-3-yl]phenol
• CAS: 1562337-07-8
• 化学式: C₂₃H₂₉N₅O
• 分子量: 391.516
• InChiKey: SJIRMWMHWILMPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.34
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  86.72
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  四甲基哌啶酮 在 2-双环己基膦-2',6'-二甲氧基联苯 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium tert-butylate 、 sodium carbonate 、 potassium carbonate 、 苯硫酚 、 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 、 N-甲基吡咯烷酮 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 39.83h， 生成 5-(1H-pyrazol-4-yl)-2-(6-((2,2,6,6-tetramethylpiperidin-4-yl)methyl)pyridazin-3-yl)phenol
  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

文献信息

• [EN] 1,4-DISUBSTITUTED PYRIDAZINE ANALOGS AND METHODS FOR TREATING SMN-DEFICIENCY-RELATED CONDITIONS<br/>[FR] ANALOGUES DE PYRIDAZINE 1,4-DISUBSTITUÉE ET PROCÉDÉS DE TRAITEMENT DE TROUBLES LIÉS À UNE DÉFICIENCE EN SMN
  申请人：NOVARTIS AG

  公开号：WO2014028459A1

  公开（公告）日：2014-02-20

  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。
• 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。
• Compounds for the treatment of cancer
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3053577A1

  公开（公告）日：2016-08-10

  The present invention relates to a FoxM1 gene splicing modifier selected from a compound of formula (I) or of formula (VI) wherein A and B are as defined herein, or a pharmaceutically acceptable salt thereof, for use in the treatment, prevention and/or delay of progression of cancer.

  本发明涉及一种选自式（I）或式（VI）化合物的 FoxM1 基因剪接修饰剂 其中 A 和 B 如本文所定义，或其药学上可接受的盐，用于治疗、预防和/或延缓癌症进展。
• 1,4-DISUBSTITUTED PYRIDAZINE COMPOUNDS FOR TREATING HUNTINGTON'S DISEASE
  申请人：PTC Therapeutics, Inc.

  公开号：EP3848035A1

  公开（公告）日：2021-07-14

  The present description relates to compounds, forms, and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease. In particular, the present description relates to substituted monocyclic heteroaryl compounds of Formula (I), forms and pharmaceutical compositions thereof and methods of using such compounds, forms, or compositions thereof for treating or ameliorating Huntington's disease.

  本说明涉及其化合物、形式和药物组合物，以及使用此类化合物、形式或组合物治疗或改善亨廷顿氏病的方法。 特别是，本说明书涉及式（I）的取代单环杂芳基化合物、其形式和药物组合物以及使用此类化合物、形式或其组合物治疗或改善亨廷顿氏病的方法。
• 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions
  申请人：NOVARTIS AG

  公开号：US10195196B2

  公开（公告）日：2019-02-05

  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。