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

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 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
• 英文别名: 1-[4-(4-amino-3-{4-[2-(morpholin-4-yl)ethoxy]phenyl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)phenyl]-3-(5-tert-butyl-1,2-oxazol-3-yl)urea；1-[4-[4-Amino-3-[4-(2-morpholin-4-ylethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]phenyl]-3-(5-tert-butyl-1,2-oxazol-3-yl)urea；1-[4-[4-amino-3-[4-(2-morpholin-4-ylethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]phenyl]-3-(5-tert-butyl-1,2-oxazol-3-yl)urea
• 化学式: C₃₁H₃₅N₉O₄
• 分子量: 597.677
• InChiKey: SKDBXDGKLQALIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  44
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-吗啉乙醇 在 四(三苯基膦)钯 、 5%-palladium/activated carbon 、 氢气 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 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
  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

文献信息

• 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。
• [EN] NOVEL INHIBITOR FOR FLT3 KINASE AND USES THEREOF<br/>[FR] NOUVEL INHIBITEUR DE LA KINASE FLT3 ET SON UTILISATION<br/>[ZH] FLT3激酶的新型抑制剂及其用途
  申请人：PRECEDO PHARMACEUTICALS CO LTD

  公开号：WO2017206962A1

  公开（公告）日：2017-12-07

  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。
• Discovery of 1-(4-(4-Amino-3-(4-(2-morpholinoethoxy)phenyl)-1<i>H</i>-pyrazolo[3,4-<i>d</i>]pyrimidin-1-yl)phenyl)-3-(5-(<i>tert</i>-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
  作者：Aoli Wang、Xixiang Li、Cheng Chen、Hong Wu、Ziping Qi、Chen Hu、Kailin Yu、Jiaxin Wu、Juan Liu、Xiaochuan Liu、Zhenquan Hu、Wei Wang、Wenliang Wang、Wenchao Wang、Li Wang、Beilei Wang、Qingwang Liu、Lili Li、Jian Ge、Tao Ren、Shanchun Zhang、Ruixiang Xia、Jing Liu、Qingsong Liu

  DOI：10.1021/acs.jmedchem.7b00840

  日期：2017.10.26

  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.
• 1-(4-(4-AMINO-3-PHENYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-1-YL)-PHENYL)-UREA DERIVATIVES AS FLT3 KINASE INHIBITORS FOR TREATING CANCER
  申请人：Precedo Pharmaceuticals Co., Ltd.

  公开号：EP3466952B1

  公开（公告）日：2021-03-03