3-iodo-1-(3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine | 1418272-74-8

• 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-(3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
• 英文别名: 3-Iodo-1-(3-nitrophenyl)pyrazolo[3,4-d]pyrimidin-4-amine
• CAS: 1418272-74-8
• 化学式: C₁₁H₇IN₆O₂
• 分子量: 382.12
• InChiKey: PWFNDMZAMYEZPI-UHFFFAOYSA-N

物化性质

• 沸点：
  493.5±45.0 °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-(3-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine 在 甲醇 、 四(三苯基膦)钯 、 potassium carbonate 、 tin(ll) chloride 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 14.0h， 生成 1-(3-aminophenyl)-3-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  Discovery of (R)-1-(3-(4-Amino-3-(3-chloro-4-(pyridin-2-ylmethoxy)phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (CHMFL-EGFR-202) as a Novel Irreversible EGFR Mutant Kinase Inhibitor with a Distinct Binding Mode

  摘要：

  On the basis of Ibrutinib's core pharmacophore, which was moderately active to EGFR T790M mutant, we discovered novel epidermal growth factor receptor (EGFR) inhibitor compound 19 (CHMFL-EGFR-202), which potently inhibited EGFR primary mutants (L858R, del19) and drug-resistant mutant L858R/T790M. Compound 19 displayed a good selectivity profile among 468 kinases/mutants tested in the KINOMEscan assay (S score (1) = 0.02). In particular, it did not exhibit apparent activities against INSR and IGF1R kinases. The X-ray crystal structure revealed that this class of inhibitors formed a covalent bond with Cys797 in a distinct "DFG-in-C-helix-out" inactive EGFR conformation. Compound 19 displayed strong antiproliferative effects against EGFR mutant-driven nonsmall cell lung cancer (NSCLC) cell lines such as H1975, PC9, HCC827, and H3255 but not the wild-type EGFR expressing cells. In the H1975 and PC9 cell-inoculated xenograft mouse models, compound 19 exhibited dose-dependent tumor growth suppression efficacy without obvious toxicity. Compound 19 might be a potential drug candidate for EGFR mutant-driven NSCLC.

  DOI：

  10.1021/acs.jmedchem.6b01907
• 作为产物：
  描述：

  间氟硝基苯 、 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， 以81.6%的产率得到3-iodo-1-(3-nitrophenyl)-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

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：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。
• US8377946B1
  申请人：——

  公开号：US8377946B1

  公开（公告）日：2013-02-19
• US9273051B2
  申请人：——

  公开号：US9273051B2

  公开（公告）日：2016-03-01
• US9546172B2
  申请人：——

  公开号：US9546172B2

  公开（公告）日：2017-01-17
• [EN] PYRAZOLO [3, 4-D] PYRIMIDINE AND PYRROLO [2, 3-D] PYRIMIDINE COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS PYRAZOLO [3, 4-D] PYRIMIDINES ET PYRROLO [2, 3-D] PYRIMIDINES EN TANT QU'INHIBITEURS DE KINASE
  申请人：PHARMACYCLICS INC

  公开号：WO2013102059A1

  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.