N-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)acetamide | 1028362-83-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)acetamide
• 英文别名: N-[5-methyl-1-(oxan-2-yl)pyrazol-3-yl]acetamide
• CAS: 1028362-83-5
• 化学式: C₁₁H₁₇N₃O₂
• 分子量: 223.275
• InChiKey: WTDYLYNESLJEHH-UHFFFAOYSA-N

物化性质

• 沸点：
  442.9±45.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)acetamide 在 水 、 potassium hydroxide 作用下， 以 乙醇 为溶剂， 反应 11.0h， 以89%的产率得到5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-amine
  参考文献：
  名称：

  用于双相情感障碍的多靶标化合物：从合理设计到初步药代动力学评估。

  摘要：

  由于双相情感障碍（BD）的复杂性和多因素性质，传统上，单靶标药物只能提供有限的缓解作用，而没有改善疾病的作用。根据多药理学范式，我们试图通过设计两个在多巴胺受体D3（D3R）上具有部分激动剂谱和对糖原合酶激酶3β（GSK-3β）的抑制活性的多目标导向配体来克服这些限制。 。这是两个在结构上不相关的目标，它们在认知和情绪调节中发挥独立但相互联系的作用。两种化合物（7和10）成为有前途的D3R /GSK-3β多靶标配体，在D3R具有纳摩尔活性，对GSK-3β具有低微摩尔抑制作用，从而初步证实了我们策略的可行性。此外，有7个在稳定性和药代动力学研究中显示出有希望的类药物特性。

  DOI：

  10.1002/cmdc.202000210
• 作为产物：
  描述：

  N-(5-甲基-1H-吡唑-3-基)-乙酰胺 、 3,4-二氢-2H-吡喃 在 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以46%的产率得到N-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)acetamide
  参考文献：
  名称：

  用于双相情感障碍的多靶标化合物：从合理设计到初步药代动力学评估。

  摘要：

  由于双相情感障碍（BD）的复杂性和多因素性质，传统上，单靶标药物只能提供有限的缓解作用，而没有改善疾病的作用。根据多药理学范式，我们试图通过设计两个在多巴胺受体D3（D3R）上具有部分激动剂谱和对糖原合酶激酶3β（GSK-3β）的抑制活性的多目标导向配体来克服这些限制。 。这是两个在结构上不相关的目标，它们在认知和情绪调节中发挥独立但相互联系的作用。两种化合物（7和10）成为有前途的D3R /GSK-3β多靶标配体，在D3R具有纳摩尔活性，对GSK-3β具有低微摩尔抑制作用，从而初步证实了我们策略的可行性。此外，有7个在稳定性和药代动力学研究中显示出有希望的类药物特性。

  DOI：

  10.1002/cmdc.202000210

文献信息

• NOVEL COMPOUNDS FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AMYLOID OR AMYLOID-LIKE PROTEINS
  申请人：Froestl Wolfgang

  公开号：US20100144793A1

  公开（公告）日：2010-06-10

  The present invention relates to compounds of the general formula (I) wherein (formula 2) independently represents a single bond or a double bond, represents a linking group A and A′ are each independently a 5- to 7-membered heterocyclic ring, wherein the heterocyclic rings A und A′ are optionally substituted by one or more substituents, selected from C 1-6 alkyl, C 3-6 cycloalkyl, optionally substituted phenyl, optionally substituted heteroaryl, C 1-4 alkylene-(optionally substituted phenyl) and C 1-4 alkylene-(optionally substituted heteroaryl), or two substituents may be joined to form an optionally substituted, saturated, unsaturated or aromatic 5- to 7-membered ring which is fused with the heterocyclic ring A or A′, and wherein the heterocyclic rings A und A′ may contain in addition to the units X, X′, Y and Y′ one or more heteroatoms, selected from N, NR, S and Ol wherein R is selected from H and C 1-4 alkyl; the units X and X′ are each independently a H-bond acceptor; and the units Y and Y′ are each independently a H-bond donor. The compound of formula (I) can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system.

  本发明涉及通式（I）的化合物，其中（式2）独立表示单键或双键，表示连接基团A和A'各自独立是5-至7-成员杂环环，其中杂环环A和A'可以选择性地被一个或多个取代基取代，所述取代基可从C1-6烷基，C3-6环烷基，可选择性取代的苯基，可选择性取代的杂环烷基，C1-4烷基烯基（可选择性取代的苯基）和C1-4烷基烯基（可选择性取代的杂环基）中选择，或者两个取代基可以连接形成一个可选择性取代的饱和、不饱和或芳香的5-至7-成员环，其与杂环环A或A'融合，杂环环A和A'除了包含单位X、X'、Y和Y'外，还可以包含一个或多个来自N、NR、S和Ol的杂原子，其中R从H和C1-4烷基中选择；单位X和X'各自独立地是H键受体；单位Y和Y'各自独立地是H键供体。通式（I）的化合物可用于治疗与淀粉样蛋白相关的一类疾病和异常，如阿尔茨海默病，以及与淀粉样蛋白相关的疾病或病况。本发明的化合物还可用于治疗与视觉系统组织中病理异常/变化相关的眼部疾病。
• N-(METHYL) -1H-PYRAZOL-3-AMINE, N-(METHYL)-PYRIDIN-2-AMINE AND N-(METHYL)-THIAZOL-2-AMINE DERIVATIVES FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AMYLOID OR AMYLOID-LIKE PROTEINS, LIKE E.G. ALZHEIMER'S
  申请人：Froestl Wolfgang

  公开号：US20100183513A1

  公开（公告）日：2010-07-22

  The present invention relates to novel compounds of formula (II) that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating, or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.

  本发明涉及式（II）的新化合物，可用于治疗与淀粉样蛋白相关的一组紊乱和异常，如阿尔茨海默病，以及与淀粉样蛋白类似的蛋白质相关的疾病或病况。本发明的化合物还可用于治疗与视觉系统组织的病理性异常/变化相关的眼部疾病。本发明还涉及包含这些化合物的制药组合物，并且涉及使用这些化合物制备用于治疗或预防与淀粉样和/或淀粉样类似蛋白质相关的疾病或病况的药物。还公开了一种治疗或预防与淀粉样和/或淀粉样类似蛋白质相关的疾病或病况的方法。
• NOVEL COMPOUND FOR THE TREATMENT OF DISEASES ASSOCIATED WITH AMYLOID OR AMYLOID-LIKE PROTEINS
  申请人：FROESTL Wolfgang

  公开号：US20120309791A1

  公开（公告）日：2012-12-06

  The present invention relates to novel compounds of formula (II) that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating, or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed

  本发明涉及公式（II）的新化合物，可用于治疗与淀粉样蛋白相关的一组疾病和异常，例如阿尔茨海默病，以及与淀粉样蛋白类似蛋白质相关的疾病或病况。本发明的化合物还可用于治疗与视觉系统组织病理异常/变化相关的眼部疾病。本发明还涉及包含这些化合物的制药组合物以及使用这些化合物制备治疗或预防与淀粉样和/或淀粉样类似蛋白质相关的疾病或病况的药物的用途。还公开了一种治疗或预防与淀粉样和/或淀粉样类似蛋白质相关的疾病或病况的方法。
• Compounds for the treatment of diseases associated with amyloid or amyloid-like proteins
  申请人：Froestl Wolfgang

  公开号：US08673940B2

  公开（公告）日：2014-03-18

  The present invention relates to novel compounds of formula (II) that can be employed in the treatment of a group of disorders and abnormalities associated with amyloid protein, such as Alzheimer's disease, and of diseases or conditions associated with amyloid-like proteins. The compounds of the present invention can also be used in the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system. The present invention further relates to pharmaceutical compositions comprising these compounds and to the use of these compounds for the preparation of medicaments for treating, or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins. A method of treating or preventing diseases or conditions associated with amyloid and/or amyloid-like proteins is also disclosed.

  本发明涉及式（II）的新化合物，可用于治疗与淀粉样蛋白相关的一组疾病和异常，如阿尔茨海默病，以及与淀粉样蛋白类似蛋白质相关的疾病或病况。本发明的化合物还可用于治疗与视觉系统组织中的病理异常/变化相关的眼部疾病。本发明还涉及包含这些化合物的制药组合物，并且涉及使用这些化合物制备用于治疗或预防与淀粉样和/或淀粉样类似蛋白质相关的疾病或病况的药物。还公开了一种治疗或预防与淀粉样和/或淀粉样类似蛋白质相关的疾病或病况的方法。
• N-(Methyl)-pyridin-2-amine derivatives for the treatment of diseases associated with amyloid or amyloid-like proteins
  申请人：AC Immune S.A.

  公开号：EP2108644B1

  公开（公告）日：2016-07-20