tert-butyl benzyl(5-((2,2-dimethyl-1,3-dioxolan-4-yl)methylamino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)carbamate | 1092444-58-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: tert-butyl benzyl(5-((2,2-dimethyl-1,3-dioxolan-4-yl)methylamino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)carbamate
• 英文别名: tert-butyl N-benzyl-N-[5-[(2,2-dimethyl-1,3-dioxolan-4-yl)methylamino]-3-propan-2-ylpyrazolo[1,5-a]pyrimidin-7-yl]carbamate
• CAS: 1092444-58-0
• 化学式: C₂₇H₃₇N₅O₄
• 分子量: 495.622
• InChiKey: GTUPRFLDLZVXAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  90.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl benzyl(5-((2,2-dimethyl-1,3-dioxolan-4-yl)methylamino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)carbamate 在 盐酸 、 甲醇 作用下， 反应 2.0h， 以98%的产率得到3-(7-(benzylamino)-3-isopropylpyrazolo[1,5-a]pyrimidin-5-ylamino)propane-1,2-diol
  参考文献：
  名称：

  WO2008/151304

  摘要：

  公开号：
• 作为产物：
  描述：

  异戊腈 在 4-二甲氨基吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 sodium 、 溶剂黄146 、 sodium t-butanolate 、 肼 、 lithium diisopropyl amide 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 反应 81.25h， 生成 tert-butyl benzyl(5-((2,2-dimethyl-1,3-dioxolan-4-yl)methylamino)-3-isopropylpyrazolo[1,5-a]pyrimidin-7-yl)carbamate
  参考文献：
  名称：

  WO2008/151304

  摘要：

  公开号：

文献信息

• [EN] PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE<br/>[FR] PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINES EN TANT QU'INHIBITEURS DE CDK ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：CANCER REC TECH LTD

  公开号：WO2015124941A1

  公开（公告）日：2015-08-27

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain pyrazolo[1,5-a]pyrimidine-5,7- diamine compounds (referred to herein as "PPDA compounds") that, inter alia, inhibit (e.g., selectively inhibit) CDK (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.). The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CDK; and to treat disorders including: disorders that are associated with CDK; disorders that result from an inappropriate activity of a cyclin-dependent kinase (CDK); disorders that are associated with CDK mutation; disorders that are associated with CDK overexpression; disorders that are associated with upstream pathway activation of CDK; disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; and cardiovascular disorders (including atherosclerosis). Optionally, the treatment further comprises treatment (e.g., simultaneous or sequential treatment) with a further active agent which is, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.

  本发明一般涉及治疗化合物领域。更具体地，本发明涉及某些吡唑并[1,5-a]嘧啶-5,7-二胺化合物（以下简称为“PPDA化合物”），其在一定程度上抑制（例如，选择性抑制）CDK（例如CDK1、CDK2、CDK4、CDK5、CDK6、CDK7、CDK8、CDK9、CDK10、CDK11、CDK12、CDK13等）。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物和组合物，无论是体外还是体内，来抑制CDK；并用于治疗包括：与CDK相关的疾病；由于细胞周期依赖性激酶（CDK）不适当活性而导致的疾病；与CDK突变相关的疾病；与CDK过表达相关的疾病；与上游通路激活CDK相关的疾病；通过抑制CDK改善的疾病；增生性疾病；癌症；病毒感染（包括HIV）；神经退行性疾病（包括阿尔茨海默病和帕金森病）；缺血；肾脏疾病；和心血管疾病（包括动脉粥样硬化）等疾病。可选地，治疗还进一步包括与另一活性药剂（例如芳香化酶抑制剂、抗雌激素、Her2阻断剂、细胞毒性化疗药物等）一起进行治疗（例如同时或顺序治疗）。
• Selective Inhibitors for Cyclin-Dependent Kinases
  申请人：Jogalekar Ashutosh S.

  公开号：US20100261683A1

  公开（公告）日：2010-10-14

  This invention provides a class of compounds which are useful for specifically inhibiting cyclin-dependent kinases. This class of compounds finds use in treating diseases resulting from inappropriate activity of cyclin-dependent kinases, including cancer, viral infections (e.g., HIV) neurodegenerative disorders (e.g. Alzheimer's disease), and cardiovascular disorders (e.g. atherosclerosis). Moreover, certain members of this class are particularly useful for inhibiting cyclin-dependent kinase 7 and are especially useful for the treatment of breast cancer.

  本发明提供了一类化合物，可用于特异性抑制细胞周期依赖性激酶。这类化合物可用于治疗由于细胞周期依赖性激酶不适当活动引起的疾病，包括癌症、病毒感染（例如HIV）、神经退行性疾病（例如阿尔茨海默病）和心血管疾病（例如动脉硬化）。此外，该类化合物的某些成员特别适用于抑制细胞周期依赖性激酶7，并且特别适用于治疗乳腺癌。
• Pyrazolo[1,5-A]pyrimidine-5,7-diamine compounds as CDK inhibitors and their therapeutic use
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US10414772B2

  公开（公告）日：2019-09-17

  Certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds that inhibit cycline dependent kinase (CDK) (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.) are disclosed. Pharmaceutical compositions comprising these compounds, and the use of these compounds and compositions to inhibit CDK; to treat disorders associated with CDK such as those arising from an inappropriate activity, mutation, overexpression, or upstream pathway activation of CDK; or disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections; neurodegenerative disorders; ischaemia; renal diseases; and cardiovascular disorders are also disclosed. Optionally, the treatment further comprises simultaneous or sequential treatment with a further active agent, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.

  本发明公开了某些吡唑并[1,5-a]嘧啶-5,7-二胺化合物，这些化合物可抑制细胞周期依赖性激酶（CDK）（如CDK1、CDK2、CDK4、CDK5、CDK6、CDK7、CDK8、CDK9、CDK10、CDK11、CDK12、CDK13等）。还公开了包含这些化合物的药物组合物，以及使用这些化合物和组合物抑制 CDK；治疗与 CDK 相关的疾病，如 CDK 的不适当活性、突变、过表达或上游途径激活引起的疾病；或通过抑制 CDK 可改善的疾病；增殖性疾病；癌症；病毒感染；神经退行性疾病；缺血；肾脏疾病；以及心血管疾病。可选地，治疗还包括同时或连续使用另一种活性剂，如芳香化酶抑制剂、抗雌激素、Her2阻断剂、细胞毒性化疗剂等。
• Pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds as CDK inhibitors and their therapeutic use
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：US10927119B2

  公开（公告）日：2021-02-23

  Certain pyrazolo[1,5-a]pyrimidine-5,7-diamine compounds that inhibit cycline dependent kinase (CDK) (e.g., CDK1, CDK2, CDK4, CDK5, CDK6, CDK7, CDK8, CDK9, CDK10, CDK11, CDK12, CDK13, etc.) are disclosed. Pharmaceutical compositions comprising these compounds, and the use of these compounds and compositions to inhibit CDK; to treat disorders associated with CDK such as those arising from an inappropriate activity, mutation, overexpression, or upstream pathway activation of CDK; or disorders that are ameliorated by the inhibition of CDK; proliferative disorders; cancer; viral infections; neurodegenerative disorders; ischaemia; renal diseases; and cardiovascular disorders are also disclosed. Optionally, the treatment further comprises simultaneous or sequential treatment with a further active agent, e.g., an aromatase inhibitor, an anti-estrogen, a Her2 blocker, a cytotoxic chemotherapeutic agent, etc.

  本发明公开了某些吡唑并[1,5-a]嘧啶-5,7-二胺化合物，这些化合物可抑制细胞周期依赖性激酶（CDK）（如CDK1、CDK2、CDK4、CDK5、CDK6、CDK7、CDK8、CDK9、CDK10、CDK11、CDK12、CDK13等）。还公开了包含这些化合物的药物组合物，以及使用这些化合物和组合物抑制 CDK；治疗与 CDK 相关的疾病，如 CDK 的不适当活性、突变、过表达或上游途径激活引起的疾病；或通过抑制 CDK 可改善的疾病；增殖性疾病；癌症；病毒感染；神经退行性疾病；缺血；肾脏疾病；以及心血管疾病。可选地，治疗还包括同时或连续使用另一种活性剂，如芳香化酶抑制剂、抗雌激素、Her2阻断剂、细胞毒性化疗剂等。
• PYRAZOLO[1,5-A]PYRIMIDINE-5,7-DIAMINE COMPOUNDS AS CDK INHIBITORS AND THEIR THERAPEUTIC USE
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：EP3107914B1

  公开（公告）日：2019-01-30