3-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine | 476371-68-3

• 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: 3-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine
• 英文别名: 3-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine；3-(1-methylethyl)-1H-Pyrazolo[3,4-d]pyrimidin-4-amine；3-propan-2-yl-2H-pyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 476371-68-3
• 化学式: C₈H₁₁N₅
• 分子量: 177.209
• InChiKey: OGZZORNTKZLPBD-UHFFFAOYSA-N

物化性质

• 沸点：
  395.6±37.0 °C(Predicted)
• 密度：
  1.323±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  80.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine 在 氨 、 四氯化锡 、 三氯氧磷 作用下， 以 甲醇 、 乙腈 为溶剂， 生成 (2S,3R,4S,5R)-2-(4-amino-3-isopropylpyrazolo[3,4-d]pyrimidin-1-yl)-5-hydroxymethyltetrahydrofuran-3,4-diol-5'-triphosphate
  参考文献：
  名称：

  Inhibitor Scaffolds as New Allele Specific Kinase Substrates

  摘要：

  The elucidation of protein kinase signaling networks is challenging due to the large size of the protein kinase superfamily (> 500 human kinases). Here we describe a new class of orthogonal triphosphate substrate analogues for the direct labeling of analogue-specific kinase protein targets. These analogues were constructed as derivatives of the Src family kinase inhibitor PP1 and were designed based on the crystal structures of PP1 bound to HCK and N-6-(benzyl)-ADP bound to c-Src (T338G). 3-Benzylpyrazolopyrimidine triphosphate (3-benzyl-PPTP) proved to be a substrate for a mutant of the MAP kinase p38 (p38-T106G/A157L/L167A). 3-Benzyl-PPTP was preferred by v-Src (T338G) (k(cat)/K-M = 3.2 x 10(6) min(-1) M-1) over ATP or the previously described ATP analogue, N-6 (benzyl) ATP. For the kinase CDK2 (F80G)/cyclin E, 3-benzyl-PPTP demonstrated catalytic efficiency (k(cat)/K-M = 2.6 x 10(4) min(-1) M-1) comparable to ATP (k(cat)/K-M = 5.0 x 10(4) min(-1) M-1) largely due to a significantly better K-M (6.4 muM vs 530 muM). In kinase protein substrate labeling experiments both 3-benzyl-PPTP and 3-phenyl-PPTP prove to be over 4 times more orthogonal than N-6-(benzyl)-ATP with respect to the wild-type kinases found in murine spleenocyte cell lysates. These experiments also demonstrate that [gamma-P-32]-3-benzyl-PPTP is an excellent phosphodonor for labeling the direct protein substrates of CDK2 (F80G)/E in murine spleenocyte cell lysates, even while competing with cellular levels (4 mM) of unlabeled ATP. The fact that this new more highly orthogonal nucleotide is accepted by three widely divergent kinases studied here suggests that it is likely to be generalizable across the entire kinase superfamily.

  DOI：

  10.1021/ja0264798
• 作为产物：
  描述：

  4-氨基吡唑并[3,4-d]嘧啶 在 N-碘代丁二酰亚胺 、 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 74.0h， 生成 3-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine
  参考文献：
  名称：

  [EN] ATG7 INHIBITORS AND THE USES THEREOF
  [FR] INHIBITEURS D'ATG7 ET LEURS UTILISATIONS

  摘要：

  本公开涉及化学实体，其为以下式（I）的化合物：或其药学上可接受的盐，其中R1、R2和Ra具有此处描述的值。根据本公开的化学实体可以用作ATG7的抑制剂。还提供了包括本公开的化学实体的药物组合物以及使用这些组合物治疗癌症的方法。

  公开号：

  WO2018089786A1

文献信息

• NOVEL COMPOUNDS AS MODULATORS OF PROTEIN KINASES
  申请人：NAGARATHNAM Dhanapalan

  公开号：US20120289496A1

  公开（公告）日：2012-11-15

  The present invention provides PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of kinase mediated diseases or disorders with them.

  本发明提供了PI3K蛋白激酶调节剂，其制备方法，含有它们的药物组合物，以及使用它们进行治疗、预防和/或改善激酶介导的疾病或紊乱的方法。
• CHEMICAL COMPOUNDS
  申请人：Axten Jeffrey Michael

  公开号：US20120077828A1

  公开（公告）日：2012-03-29

  The invention is directed to substituted indoline derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R 1 , R 2 , and R 3 are defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, ocular diseases, and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, Type 1 diabetes Parkinson disease, Huntington's disease, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, atherosclerosis, and arrhythmias, and more specifically cancers of the breast, colon, pancreatic, and lung. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

  本发明涉及取代的吲哚啉衍生物。具体而言，本发明涉及按式I所示的化合物：其中R1、R2和R3在此定义。本发明的化合物是PERK的抑制剂，可用于治疗癌症、眼部疾病和与激活的未折叠蛋白质应答途径相关的疾病，如阿尔茨海默病、中风、1型糖尿病帕金森病、亨廷顿病、肌萎缩性侧索硬化、心肌梗死、心血管疾病、动脉硬化和心律失常，更具体地，乳腺癌、结肠癌、胰腺癌和肺癌。因此，本发明进一步涉及包含本发明化合物的药物组合物。本发明还涉及使用本发明化合物或包含本发明化合物的药物组合物抑制PERK活性和治疗相关疾病的方法。
• Compounds as modulators of protein kinases
  申请人：Rhizen Pharmaceuticals SA

  公开号：US10220035B2

  公开（公告）日：2019-03-05

  The present invention provides PI3K protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of kinase mediated diseases or disorders with them.

  本发明提供了 PI3K 蛋白激酶调节剂、制备方法、含有这些调节剂的药物组合物以及用它们治疗、预防和/或改善激酶介导的疾病或紊乱的方法。
• Substituted chromenones as modulators of protein kinases
  申请人：Rhizen Pharmaceuticals SA

  公开号：US10322130B2

  公开（公告）日：2019-06-18

  The present invention provides PI3K protein kinase modulators of formula wherein R, Cy1, R1, R2, L1 and Cy2 are as defined herein. The present invention also relates to methods of preparing compounds of formula (I) to pharmaceutical compositions containing them and to methods of treatment, prevention and/or amelioration of kinase mediated diseases or disorders with them.

  本发明提供式 PI3K 蛋白激酶调节剂，其中 R、Cy1、R1、R2、L1 和 Cy2 如本文所定义。 本发明还涉及制备式（I）化合物的方法、含有式（I）化合物的药物组合物以及用式（I）化合物治疗、预防和/或改善激酶介导的疾病或紊乱的方法。
• ATG7 inhibitors and the uses thereof
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US10865208B2

  公开（公告）日：2020-12-15

  Disclosed are chemical entities which are compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2, and Ra have the values described herein. Chemical entities according to the disclosure can be useful as inhibitors of ATG7. Further provided are pharmaceutical compositions comprising a chemical entity of the disclosure and methods of using the compositions in the treatment of cancer.

  所公开的化学实体为式（I）化合物：或其药学上可接受的盐，其中 R1、R2 和 Ra 具有本文所述的值。根据本公开的化学实体可用作 ATG7 的抑制剂。进一步提供了包含本公开的化学实体的药物组合物，以及使用该组合物治疗癌症的方法。