3-iodo-1-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine | 330793-99-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-iodo-1-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• 英文别名: 3-iodo-1-(4-nitrophenyl)pyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 330793-99-2
• 化学式: C₁₁H₇IN₆O₂
• 分子量: 382.12
• InChiKey: SSELDJQDQBTJOE-UHFFFAOYSA-N

物化性质

• 沸点：
  500.7±50.0 °C(Predicted)
• 密度：
  2.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-iodo-1-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 在 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 16.0h， 生成 1-(4-aminophenyl)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  Discovery of 1-(4-(4-Amino-3-(4-(2-morpholinoethoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl)-3-(5-(tert-butyl)isoxazol-3-yl)urea (CHMFL-FLT3-213) as a Highly Potent Type II FLT3 Kinase Inhibitor Capable of Overcoming a Variety of FLT3 Kinase Mutants in FLT3-ITD Positive AML

  摘要：

  FLT3-ITD mutant has been observed in about 30% of AML patients and extensively studied as a drug discovery target. On the basis of our previous study that ibrutinib (9) exhibited selective and moderate inhibitory activity against FLT3-ITD positive AML cells, through a structure-guided drug design approach, we have discovered a new type II FLT3 kinase inhibitor, compound 14 (CHMFL-FLT3-213), which exhibited highly potent inhibitory effects against FLT3TTD mutant and associated oncogenic mutations (including FLT3-D835Y/H/V, FLT3-ITD-D835Y/I/N/A/G/Del, and FLT3-ITD-F691L). In the cellular context 14 strongly affected FLT3-TTD mediated signaling pathways and induced apoptosis by arresting cell cycle into G0/G1 phase. In the in vivo studies 14 demonstrated an acceptable bioavaOability (F = 19%) and significantly suppressed the tumor growth in MV4-11 cell inoculated xenograft model (15 mg kg(-1) day(-1), TGI = 97%) without exhibiting obvious toxicity. Compound 14 might be a potential drug candidate for FLT3-TTD positive AML.

  DOI：

  10.1021/acs.jmedchem.7b00840
• 作为产物：
  描述：

  对氟硝基苯 、 3-碘-4-氨基吡唑并[3,4-d]嘧啶 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以6 g的产率得到3-iodo-1-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  FLT3激酶的新型抑制剂及其用途

  摘要：

  本发明提供FLT3激酶的新型抑制剂，其包括式(I)的化合物或其药学可接受的盐、溶剂化物、异构体、酯、酸、代谢物、或前药。本发明还提供包括式(I)化合物的药物组合物，以及其用于预防或治疗与FLT3相关的病症的用途和方法，特别是与突变型FLT3激酶(尤其是FLT3/ITD突变型激酶)相关的病症。

  公开号：

  CN107459521B
• 作为试剂：
  描述：

  3-碘-4-氨基吡唑并[3,4-d]嘧啶 、 Dicaesio carbonate 、 对氟硝基苯 、 乙酸铵 在 氮 、 ice 、 水 、 3-iodo-1-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 作用下， 以 N,N-二甲基甲酰胺 、 水 、 乙腈 为溶剂， 反应 21.08h， 以to give 2.55 g (87%)的产率得到3-iodo-1-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  Pyrazolopyrimidines as therapeutic agents

  摘要：

  本发明涉及式(I)的吡唑吡咯啉衍生物，其中取代基在此定义，它们可用作激酶抑制剂，因此可用于影响血管生成及与血管生成相关的疾病和病况。

  公开号：

  US06921763B2

文献信息

• Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors
  申请人：Chen Wei

  公开号：US08377946B1

  公开（公告）日：2013-02-19

  Disclosed herein are compounds of Formula (II) that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

  本文披露的是与布鲁顿酪氨酸激酶（Btk）形成共价键的化合物（II）的公式。还描述了Btk的不可逆抑制剂。披露了制备这些化合物的方法。还披露了包括这些化合物的药物组合物。披露了使用Btk抑制剂的方法，单独或与其他治疗剂一起，用于治疗自身免疫疾病或症状、异种免疫疾病或症状、包括淋巴瘤在内的癌症，以及炎症性疾病或症状。
• PYRAZOLO[3,4-d]PYRIMIDINE AND PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS AS KINASE INHIBITORS
  申请人：CHEN Wei

  公开号：US20130172314A1

  公开（公告）日：2013-07-04

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

  本文披露了一些与布鲁顿酪氨酸激酶（Btk）形成共价键的化合物。还描述了Btk的不可逆抑制剂。披露了制备这些化合物的方法。还披露了包括这些化合物的制药组合物。披露了使用Btk抑制剂的方法，单独或与其他治疗剂一起治疗自身免疫性疾病或病况、异种免疫性疾病或病况、癌症（包括淋巴瘤）和炎症性疾病或病况。
• PYRAZOLO[3,4-d]PYRIMIDINE AND PYRAZOLO[2,3-d]PYRIMIDINE COMPOUNDS AS KINASE INHIBITORS
  申请人：Pharmacyclics, Inc.

  公开号：US20150018336A1

  公开（公告）日：2015-01-15

  Disclosed herein are compounds that form covalent bonds with Bruton's tyrosine kinase (Btk). Also described are irreversible inhibitors of Btk. Methods for the preparation of the compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the Btk inhibitors are disclosed, alone or in combination with other therapeutic agents, for the treatment of autoimmune diseases or conditions, heteroimmune diseases or conditions, cancer, including lymphoma, and inflammatory diseases or conditions.

  本文披露了一些与布鲁顿酪氨酸激酶（Btk）形成共价键的化合物。同时，还描述了Btk的不可逆抑制剂。公开了制备这些化合物的方法。还公开了包括这些化合物的药物组合物。公开了使用Btk抑制剂的方法，单独或与其他治疗剂联合使用，用于治疗自身免疫性疾病或病况，异种免疫性疾病或病况，包括淋巴瘤的癌症和炎症性疾病或病况。
• NOVEL INHIBITOR FOR FLT3 KINASE AND USES THEREOF
  申请人：Precedo Pharmaceuticals Co., Ltd.

  公开号：EP3466952A1

  公开（公告）日：2019-04-10

  The present invention provides a novel inhibitor of FLT3 kinase, comprising a compound of formula (I) or a pharmaceutically acceptable salt, solvate, isomer, ester, acid, metabolite or prodrug thereof. The present invention also provides a pharmaceutical composition comprising the compound of formula (I), as well as the use and method for preventing or treating FLT3-related conditions, especially conditions related to mutant FLT3 kinase (particularly, FLT3/ITD mutant kinase).

  本发明提供了一种新型的FLT3激酶抑制剂，包括式（I）化合物或其药学上可接受的盐、溶液剂、异构体、酯、酸、代谢物或原药。本发明还提供了一种包含式（I）化合物的药物组合物，以及预防或治疗FLT3相关病症，特别是与突变FLT3激酶（尤其是FLT3/ITD突变激酶）相关病症的用途和方法。
• Inhibitor of FLT3 kinase and use thereof
  申请人：PRECEDO PHARMACEUTICALS CO., LTD

  公开号：US10975082B2

  公开（公告）日：2021-04-13

  The present invention provides a novel inhibitor of FLT3 kinase, comprising a compound of formula (I) or a pharmaceutically acceptable salt, solvate, isomer, ester, acid, metabolite or prodrug thereof. The present invention also provides a pharmaceutical composition comprising the compound of formula (I), as well as the use and method for preventing or treating FLT3-related conditions, especially conditions related to mutant FLT3 kinase (particularly, FLT3/ITD mutant kinase).

  本发明提供了一种新型的FLT3激酶抑制剂，包括式（I）化合物或其药学上可接受的盐、溶液剂、异构体、酯、酸、代谢物或原药。本发明还提供了一种包含式（I）化合物的药物组合物，以及预防或治疗FLT3相关病症，特别是与突变FLT3激酶（尤其是FLT3/ITD突变激酶）相关病症的用途和方法。