5,7-Diamino-pyrazolo<1,5-a>pyrimidin | 95650-17-2

• 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: 5,7-Diamino-pyrazolo<1,5-a>pyrimidin
• 英文别名: 5,7-Diamino-pyrazolo[1,5-a]pyrimidin；Pyrazolo[1,5-a]pyrimidine-5,7-diamine
• CAS: 95650-17-2
• 化学式: C₆H₇N₅
• mdl: MFCD16619828
• 分子量: 149.155
• InChiKey: GLWUDZAXMREBCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  二乙基丙烷二亚氨酸酯二盐酸盐 、 3-氨基吡唑 以 乙醇 为溶剂， 反应 5.0h， 以63%的产率得到5,7-Diamino-pyrazolo<1,5-a>pyrimidin
  参考文献：
  名称：

  Synthese von 5,7-Diaminopyrazolo[1,5-a]pyrimidinen

  摘要：

  DOI：

  10.1002/ardp.19853180116

文献信息

• [EN] 4-[[(7-AMINOPYRAZOLO[1,5-A]PYRIMIDIN-5-YL)AMINO]METHYL]PIPERIDIN-3-OL COMPOUNDS AS CDK INHIBITORS<br/>[FR] COMPOSÉS DE 4-[[(7-AMINOPYRAZOLO[1,5-A]PYRIMIDIN-5-YL)AMINO]MÉTHYL]PIPÉRIDIN-3-OL UTILISÉS EN TANT QU'INHIBITEURS DE CDK
  申请人：CARRICK THERAPEUTICS LTD

  公开号：WO2019057825A1

  公开（公告）日：2019-03-28

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 4-[[(7-aminopyrazolo[1,5- a]pyrimidin-5-yl)amino]methyl]piperidin-3-ol compounds (referred to herein as "APPAMP 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; cardiovascular disorders (including atherosclerosis); and autoimmune disorders (including rheumatoid arthritis). 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4-[[(7-氨基吡唑[1,5-a]嘧啶-5-基)氨基]甲基]哌啶-3-醇化合物（以下简称为“APPAMP化合物”），该化合物在某种程度上抑制（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种化合物的药物组合物，以及使用这种化合物和组合物在体外和体内抑制CDK；以及治疗包括的疾病：与CDK相关的疾病；由于细胞周期依赖性激酶（CDK）的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CDK上游途径激活相关的疾病；通过抑制CDK改善的疾病；增殖性疾病；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；心血管疾病（包括动脉粥样硬化）；以及自身免疫性疾病（包括类风湿性关节炎）。可选地，治疗还包括与另一活性剂（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）的治疗（例如，同时或顺序治疗）。
• [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）。
• [EN] 4-[[(7-AMINOPYRAZOLO[1,5-A]PYRIMIDIN-5-YL)AMINO]METHYL]PIPERIDIN-3-OL COMPOUNDS AND THEIR THERAPEUTIC USE<br/>[FR] COMPOSÉS DE 4-[[(7-AMINOPYRAZOLO[1,5-A]PYRIMIDIN-5-YL)AMINO]MÉTHYL]PIPÉRIDIN-3-OL ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：CARRICK THERAPEUTICS LTD

  公开号：WO2021122745A1

  公开（公告）日：2021-06-24

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain H-APPAMP compounds (referred to herein as "H-APPAMP compounds") that, inter alia, inhibit cyclin-dependent protein kinases (CDKs), especially CDK12 and/or CDK13, and are selective, for example, for CDK12 and/or CDK13 as compared to CDK7. In addition to selectively inhibiting CDK12 and/or CDK13, the compounds also act as selective Cyclin K degraders thereby removing the key signaling mechanism required for CDK12 and/or CDK13 activation; this confers additional cellular potency and selectivity. 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, especially CDK12 and/or CDK13; and to treat disorders including: disorders that are associated with CDK, especially CDK12 and/or CDK13; disorders that result from an inappropriate activity of a CDK, especially CDK12 and/or CDK13; disorders that are associated with CDK mutation, especially CDK12 and/or CDK13mutation; disorders that are associated with CDK overexpression, especially CDK12 and/or CDK13 overexpression; disorders that are associated with upstream pathway activation of CDK, especially CDK12 and/or CDK13; disorders that are ameliorated by the inhibition of CDK, especially CDK12 and/or CDK13; proliferative disorders; cancer; viral infections (including HIV); neurodegenerative disorders (including Alzheimer's disease and Parkinson's disease); ischaemia; renal diseases; cardiovascular disorders (including atherosclerosis); autoimmune disorders (including rheumatoid arthritis); and disorders caused by dysfunction of translation in cells (including muscular dystrophy). 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, an anti-androgen, a Her2 blocker, a cytotoxic chemotherapeutic agent, an agent stimulating the immune system, a checkpoint inhibitor, a DMA repair inhibitor, 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H-APPAMP化合物（以下简称为“H-APPAMP化合物”），其中包括抑制细胞周期依赖性蛋白激酶（CDKs），特别是CDK12和/或CDK13，并且具有选择性，例如与CDK7相比，对CDK12和/或CDK13有选择性。除了选择性地抑制CDK12和/或CDK13外，这些化合物还作为选择性的Cyclin K降解物，从而去除了CDK12和/或CDK13激活所需的关键信号机制；这赋予了额外的细胞效力和选择性。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，无论是在体外还是在体内，来抑制CDK，特别是CDK12和/或CDK13；以及治疗包括以下疾病的疾病：与CDK有关的疾病，特别是与CDK12和/或CDK13有关的疾病；由于CDK不恰当活性导致的疾病，特别是由于CDK12和/或CDK13不恰当活性导致的疾病；与CDK突变有关的疾病，特别是与CDK12和/或CDK13突变有关的疾病；与CDK过度表达有关的疾病，特别是与CDK12和/或CDK13过度表达有关的疾病；与CDK上游途径激活有关的疾病，特别是与CDK12和/或CDK13上游途径激活有关的疾病；通过抑制CDK改善的疾病，特别是通过抑制CDK12和/或CDK13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；心血管疾病（包括动脉粥样硬化）；自身免疫性疾病（包括类风湿性关节炎）；以及由细胞中翻译功能失调引起的疾病（包括肌肉萎缩症）的疾病。可选地，治疗进一步包括与另一活性药剂的治疗（例如同时或顺序治疗），该药剂可以是芳香化酶抑制剂、抗雌激素、抗雄激素、Her2阻断剂、细胞毒化疗药物、刺激免疫系统的药剂、检查点抑制剂、DNA修复抑制剂等。
• 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：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。