1-(4-溴-1,3-噻唑-2-基)哌啶-4-甲酰胺 | 1289198-96-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 1-(4-溴-1,3-噻唑-2-基)哌啶-4-甲酰胺
• 英文名称: 1-(4-bromothiazol-2-yl)piperidine-4-carboxamide
• 英文别名: 1-(4-bromo-1,3-thiazol-2-yl)piperidine-4-carboxamide
• CAS: 1289198-96-4
• 化学式: C₉H₁₂BrN₃OS
• 分子量: 290.184
• InChiKey: NEPQTVXDRWJSMP-UHFFFAOYSA-N

物化性质

• 沸点：
  487.5±55.0 °C(Predicted)
• 密度：
  1.621±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  87.5
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934100090

反应信息

• 作为反应物：
  描述：

  1-(4-溴-1,3-噻唑-2-基)哌啶-4-甲酰胺 、 4-三氟甲氧基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 水 为溶剂， 反应 0.5h， 生成 1-(4-(4-(trifluoromethoxy)phenyl)thiazol-2-yl)piperidine-4-carboxamide
  参考文献：
  名称：

  Discovery, Synthesis, and Biological Evaluation of Novel SMN Protein Modulators

  摘要：

  Spinal muscular atrophy (SMA) is an autosomal recessive disorder affecting the expression or function of survival motor neuron protein (SMN) due to the homozygous deletion or rare point mutations in the survival motor neuron gene 1 (SMN1). The human genome includes a second nearly identical gene called SMN2 that is retained in SMA. SMN2 transcripts undergo alternative splicing with reduced levels of SMN, Up-regulation of SMN2 expression, modification of its splicing, or inhibition of proteolysis of the truncated protein derived from SMN2 have been discussed as potential therapeutic strategies for SMA. In this manuscript, we detail the discovery of a series of arylpiperidines as novel modulators of SMN protein. Systematic hit-to-lead efforts significantly improved potency and efficacy of the series in the primary and orthogonal assays. Structure-property relationships including microsomal stability, cell permeability, and in vivo pharmacokinetics (PK) studies were also investigated. We anticipate that a lead candidate chosen from this series may serve as a useful probe for exploring the therapeutic benefits of SMN protein up-regulation in SMA animal models and a starting point for clinical development.

  DOI：

  10.1021/jm200497t
• 作为产物：
  描述：

  哌啶-4-甲酰胺 、 2,4-二溴噻唑 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以85%的产率得到1-(4-溴-1,3-噻唑-2-基)哌啶-4-甲酰胺
  参考文献：
  名称：

  [EN] ARYLTHIAZOLYL PIPERIDINES AND RELATED COMPOUNDS AS MODULATORS OF SURVIVAL MOTOR NEURON (SMN) PROTEIN PRODUCTION
  [FR] ARYLTHIAZOLYL PIPÉRIDINES ET COMPOSÉS ASSOCIÉS COMME MODULATEURS DE LA PRODUCTION DE PROTÉINE DE NEURONE MOTEUR DE SURVIE (SMN)

  摘要：

  本文提供了取代基为芳基的噻唑-2-基哌啶和相关化合物，可用作调节存活运动神经元（SMN）蛋白产生的调节剂。虽然不受任何特定理论的约束，但人们认为本文提供的取代基为芳基的噻唑-2-基哌啶和相关化合物可增加存活运动神经元蛋白的SMN2形式的产生。这些化合物适用于治疗脊髓性肌萎缩症。本文还提供了含有载体和本文所述的一种或多种取代基为芳基的噻唑-2-基哌啶或相关化合物的药物组合物。本公开还提供了治疗脊髓性肌萎缩症的方法。

  公开号：

  WO2011130515A1

文献信息

• [EN] ARYLTHIAZOLYL PIPERIDINES AND RELATED COMPOUNDS AS MODULATORS OF SURVIVAL MOTOR NEURON (SMN) PROTEIN PRODUCTION<br/>[FR] ARYLTHIAZOLYL PIPÉRIDINES ET COMPOSÉS ASSOCIÉS COMME MODULATEURS DE LA PRODUCTION DE PROTÉINE DE NEURONE MOTEUR DE SURVIE (SMN)
  申请人：US HEALTH

  公开号：WO2011130515A1

  公开（公告）日：2011-10-20

  Aryl substituted thiazol-2-yl-piperidines and related compounds useful as modulators of survival motor neuron (SMN) protein production are provided herein. Without being bound to any particular theory it is believed the aryl substituted thiazol-2-yl-piperidines and related compounds provided herein act to increase production of the SMN2 form of survival motor neuron protein. These compounds are useful for treating spinal muscular atrophy. Pharmaceutical compositions containing a carrier and one or more of the aryl substituted thiazol-2-yl-piperidine or related compounds described herein are also provided. Methods of treating spinal muscular atrophy are also provided by this disclosure.

  本文提供了取代基为芳基的噻唑-2-基哌啶和相关化合物，可用作调节存活运动神经元（SMN）蛋白产生的调节剂。虽然不受任何特定理论的约束，但人们认为本文提供的取代基为芳基的噻唑-2-基哌啶和相关化合物可增加存活运动神经元蛋白的SMN2形式的产生。这些化合物适用于治疗脊髓性肌萎缩症。本文还提供了含有载体和本文所述的一种或多种取代基为芳基的噻唑-2-基哌啶或相关化合物的药物组合物。本公开还提供了治疗脊髓性肌萎缩症的方法。
• ARYLTHIAZOLYL PIPERIDINES AND RELATED COMPOUNDS AS MODULATORS OF SURVIVAL MOTOR NEURON (SMN) PROTEIN PRODUCTION
  申请人：Marugan Juan Jose

  公开号：US20130096160A1

  公开（公告）日：2013-04-18

  Aryl substituted thiazol-2-yl-piperidines and related compounds useful as modulators of survival motor neuron (SMN) protein production are provided herein. Without being bound to any particular theory it is believed the aryl substituted thiazol-2-yl-piperidines and related compounds provided herein act to increase production of the SMN2 form of survival motor neuron protein. These compounds are useful for treating spinal muscular atrophy. Pharmaceutical compositions containing a carrier and one or more of the aryl substituted thiazol-2-yl-piperidine or related compounds described herein are also provided. Methods of treating spinal muscular atrophy are also provided by this disclosure.

  本文提供了取代芳基噻唑-2-基哌啶和相关化合物，可用作生存运动神经元（SMN）蛋白质产生的调节剂。不受任何特定理论的约束，据信本文提供的取代芳基噻唑-2-基哌啶和相关化合物可增加生存运动神经元蛋白质的SMN2形式的产生。这些化合物可用于治疗脊髓性肌萎缩症。本文还提供了含有载体和本文所述的一个或多个取代芳基噻唑-2-基哌啶或相关化合物的制药组合物。本文还提供了治疗脊髓性肌萎缩症的方法。
• Discovery, Synthesis, and Biological Evaluation of Novel SMN Protein Modulators
  作者：Jingbo Xiao、Juan J. Marugan、Wei Zheng、Steve Titus、Noel Southall、Jonathan J. Cherry、Matthew Evans、Elliot J. Androphy、Christopher P. Austin

  DOI：10.1021/jm200497t

  日期：2011.9.22

  Spinal muscular atrophy (SMA) is an autosomal recessive disorder affecting the expression or function of survival motor neuron protein (SMN) due to the homozygous deletion or rare point mutations in the survival motor neuron gene 1 (SMN1). The human genome includes a second nearly identical gene called SMN2 that is retained in SMA. SMN2 transcripts undergo alternative splicing with reduced levels of SMN, Up-regulation of SMN2 expression, modification of its splicing, or inhibition of proteolysis of the truncated protein derived from SMN2 have been discussed as potential therapeutic strategies for SMA. In this manuscript, we detail the discovery of a series of arylpiperidines as novel modulators of SMN protein. Systematic hit-to-lead efforts significantly improved potency and efficacy of the series in the primary and orthogonal assays. Structure-property relationships including microsomal stability, cell permeability, and in vivo pharmacokinetics (PK) studies were also investigated. We anticipate that a lead candidate chosen from this series may serve as a useful probe for exploring the therapeutic benefits of SMN protein up-regulation in SMA animal models and a starting point for clinical development.