2-[((2S)-1-ethylpyrrolidin-2-yl)methoxy]-6-bromonaphthalene | 851762-66-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[((2S)-1-ethylpyrrolidin-2-yl)methoxy]-6-bromonaphthalene
• 英文别名: (2S)-2-[(6-bromonaphthalen-2-yl)oxymethyl]-1-ethylpyrrolidine
• CAS: 851762-66-8
• 化学式: C₁₇H₂₀BrNO
• 分子量: 334.256
• InChiKey: WNARYWNZFKOVDK-INIZCTEOSA-N

物化性质

• 沸点：
  428.2±15.0 °C(Predicted)
• 密度：
  1.300±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[((2S)-1-ethylpyrrolidin-2-yl)methoxy]-6-bromonaphthalene 、 二氯甲烷 、 potassium acetate 、 、 、 3-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carbonitrile 、 potassium carbonate 、 在 3-{6-[((2S)-1-ethylpyrrolidin-2-yl)methoxy](2-naphthyl)}-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile 、 1,1′-bis(diphenylphosphinoferrocene) 、 silica gel 、 methanol-dichloromethane 作用下， 以 N,N-二甲基甲酰胺 、 乙酸乙酯 为溶剂， 反应 19.0h， 以to afford the title compound (1.05 g., 16% yield)的产率得到3-{6-[((2S)-1-ethylpyrrolidin-2-yl)methoxy](2-naphthyl)}-1-perhydro-2H-pyran-2-yl-1H-indazole-5-carbonitrile
  参考文献：
  名称：

  Methods of treating diseases and disorders by targeting multiple kinases

  摘要：

  本发明涉及使用单一药剂，该药剂能同时靶向两个或更多的激酶，从而大大避免对治疗的抵抗。本发明提供了一种方法，用于使用、管理和治疗与两个或更多激酶活动相关的各种疾病或状况的个体，包括单一药剂的使用，单独或与其他治疗该疾病或状况的疗法联合使用。

  公开号：

  US20050107386A1
• 作为产物：
  描述：

  6-溴-2-萘酚 、 (S)-1-ethyl-2-hydroxymethylpyrrolidine 在 bis(1,1-dimethylethyl)-1,2-diazenedicarboxylate 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 以100%的产率得到2-[((2S)-1-ethylpyrrolidin-2-yl)methoxy]-6-bromonaphthalene
  参考文献：
  名称：

  Methods of treating diseases and disorders by targeting multiple kinases

  摘要：

  本发明涉及使用单一药剂，这些药剂是同时靶向两个或更多激酶的化合物，从而大大避免对治疗的抵抗。该发明提供了用于治疗与两个或更多激酶活性相关的各种疾病或病况的方法，包括给予一个或多个单一药剂的给药、管理和治疗，可以单独使用，也可以与其他治疗同一疾病或病况的疗法结合使用。

  公开号：

  US20050107386A1
• 作为试剂：
  描述：

  6-溴-2-萘酚 、 (S)-1-ethyl-2-hydroxymethylpyrrolidine 、 三苯基膦 、 、 在 2-[((2S)-1-ethylpyrrolidin-2-yl)methoxy]-6-bromonaphthalene 、 三苯基氧化膦 、 resultant filtrate 、 silica gel 、 methanol-dichloromethane 作用下， 以 四氢呋喃 为溶剂， 反应 0.42h， 以to afford the title compound (11.0 g., >100% yield)的产率得到2-[((2S)-1-ethylpyrrolidin-2-yl)methoxy]-6-bromonaphthalene
  参考文献：
  名称：

  Methods of treating diseases and disorders by targeting multiple kinases

  摘要：

  本发明涉及使用单一药剂，该药剂能同时靶向两个或更多的激酶，从而大大避免对治疗的抵抗。本发明提供了一种方法，用于使用、管理和治疗与两个或更多激酶活动相关的各种疾病或状况的个体，包括单一药剂的使用，单独或与其他治疗该疾病或状况的疗法联合使用。

  公开号：

  US20050107386A1

文献信息

• Indazole compounds and methods of use thereof
  申请人：Bhagwat S. Shripad

  公开号：US20060004043A1

  公开（公告）日：2006-01-05

  This invention is directed to Indazole Compounds or pharmaceutically acceptable salts, solvates and hydrates thereof. The Indazole Compounds have utility in the treatment or prevention of a wide range of diseases and disorders that are responsive to the inhibition, modulation or regulation of kinases, such as inflammatory diseases, abnormal angiogenesis and diseases related thereto, cancer, atherosclerosis, a cardiovascular disease, a renal disease, an autoimmune condition, macular degeneration, disease-related wasting, an asbestos-related condition, pulmonary hypertension, diabetes, obesity, pain and others. Thus, methods of treating or preventing such diseases and disorders are also disclosed, as are pharmaceutical compositions comprising one or more of the Indazole Compounds. This invention is based, in part, upon the discovery of a novel class of 5-triazolyl substituted indazole molecules that have potent activity with respect to the modulation of protein kinases. Thus, the invention encompasses orally active molecules as well as parenterally active molecules which can be used at lower doses or serum concentrations for treating diseses or disorders associated with protein kinase signal transduction.

  本发明涉及吲唑化合物或其药学上可接受的盐、溶剂合物和水合物。这些吲唑化合物在治疗或预防广泛的疾病和紊乱方面具有实用性，这些疾病和紊乱对激酶的抑制、调节或调控具有反应性，例如炎症性疾病、异常血管生成及相关疾病、癌症、动脉硬化、心血管疾病、肾脏疾病、自身免疫疾病、黄斑变性、与疾病有关的消耗、石棉相关疾病、肺动脉高压、糖尿病、肥胖症、疼痛和其他疾病。因此，本发明还揭示了治疗或预防此类疾病和紊乱的方法，以及包含一种或多种吲唑化合物的药物组成物。本发明部分基于发现一类新型的5-三唑基取代吲唑分子，它们在蛋白激酶调节方面具有强效活性。因此，本发明包括口服活性分子以及可用于治疗与蛋白激酶信号转导相关的疾病或紊乱的肠外活性分子，其剂量或血清浓度较低。
• INDAZOLE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Bhagwat Shripad S.

  公开号：US20090099178A1

  公开（公告）日：2009-04-16

  This invention is directed to Indazole Compounds or pharmaceutically acceptable salts, solvates and hydrates thereof. The Indazole Compounds have utility in the treatment or prevention of a wide range of diseases and disorders that are responsive to the inhibition, modulation or regulation of kinases, such as inflammatory diseases, abnormal angiogenesis and diseases related thereto, cancer, atherosclerosis, a cardiovascular disease, a renal disease, an autoimmune condition, macular degeneration, disease-related wasting, an asbestos-related condition, pulmonary hypertension, diabetes, obesity, pain and others. Thus, methods of treating or preventing such diseases and disorders are also disclosed, as are pharmaceutical compositions comprising one or more of the Indazole Compounds. This invention is based, in part, upon the discovery of a novel class of 5-triazolyl substituted indazole molecules that have potent activity with respect to the modulation of protein kinases. Thus, the invention encompasses orally active molecules as well as parenterally active molecules which can be used at lower doses or serum concentrations for treating diseases or disorders associated with protein kinase signal transduction.

  本发明涉及吲唑化合物或其药学上可接受的盐、溶剂合物和水合物。这些吲唑化合物在治疗或预防许多对激酶的抑制、调节或调控具有反应性的疾病和障碍方面具有用途，例如炎症性疾病、异常血管生成及相关疾病、癌症、动脉粥样硬化、心血管疾病、肾脏疾病、自身免疫疾病、黄斑变性、与疾病相关的消耗、石棉相关疾病、肺动脉高压、糖尿病、肥胖症、疼痛等。因此，本发明还揭示了治疗或预防这些疾病和障碍的方法，以及包含一种或多种吲唑化合物的制药组合物。本发明部分基于发现一类新型的5-三唑基取代吲唑分子，这些分子在调节蛋白激酶方面具有强效活性。因此，本发明包括口服活性分子和经肠道给药的活性分子，可用于治疗与蛋白激酶信号转导相关的疾病或障碍，且可用较低剂量或血清浓度。
• Indazole compounds and methods of use thereof as protein kinase inhibitors
  申请人：SIGNAL PHARMACEUTICALS, INC.

  公开号：EP2065383A1

  公开（公告）日：2009-06-03

  This invention is directed to Indazole Compounds or pharmaceutically acceptable salts, solvates and hydrates thereof. The Indazole Compounds have utility in the treatment or prevention of a wide range of diseases and disorders that are responsive to the inhibition, modulation or regulation of kinases, such as inflammatory diseases, abnormal angiogenesis and diseases related thereto, cancer, atherosclerosis, a cardiovascular disease, a renal disease, an autoimmune condition, macular degeneration, disease-related wasting, an asbestos-related condition, pulmonary hypertension, diabetes, obesity, pain and others. Thus, methods of treating or preventing such diseases and disorders are also disclosed, as are pharmaceutical compositions comprising one or more of the Indazole Compounds. This invention is based, in part, upon the discovery of a novel class of 5-triazolyl substituted indazole molecules that have potent activity with respect to the modulation of protein kinases. Thus, the invention encompasses orally active molecules as well as parenterally active molecules which can be used at lower doses or serum concentrations for treating diseses or disorders associated with protein kinase signal transduction.

  本发明涉及吲唑化合物或其药学上可接受的盐、溶液剂和水合物。吲唑化合物可用于治疗或预防对激酶的抑制、调节或调控有反应的多种疾病和失调，如炎症性疾病、异常血管生成及其相关疾病、癌症、动脉粥样硬化、心血管疾病、肾脏疾病、自身免疫性疾病、黄斑变性、与疾病相关的消瘦、与石棉相关的疾病、肺动脉高压、糖尿病、肥胖症、疼痛等。因此，本发明还公开了治疗或预防此类疾病和失调的方法，以及包含一种或多种吲唑化合物的药物组合物。本发明部分基于对一类新型 5-三唑取代的吲唑分子的发现，该类分子在调节蛋白激酶方面具有强效活性。因此，本发明包括口服活性分子和肠外活性分子，这些分子可以较低的剂量或血清浓度用于治疗与蛋白激酶信号转导有关的疾病或紊乱。
• INDAZOLE COMPOUNDS AND METHODS OF USE THEREOF AS PROTEIN KINASE INHIBITORS
  申请人：Signal Pharmaceuticals LLC

  公开号：EP1692128A1

  公开（公告）日：2006-08-23
• EP1791831A4
  申请人：——

  公开号：EP1791831A4

  公开（公告）日：2009-07-08