(S)-5-(4-(3-methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并三嗪类
• 英文名称: (S)-5-(4-(3-methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine
• 英文别名: 5-[4-[(3S)-3-methylmorpholin-4-yl]-6-[(4-methylsulfonylpiperazin-1-yl)methyl]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-4-(trifluoromethyl)pyridin-2-amine
• 化学式: C₂₃H₂₉F₃N₈O₃S
• 分子量: 554.596
• InChiKey: AFUFOYSAHFAROX-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (S)-5-(4-(3-methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine 在 三乙胺 作用下， 以 四氢呋喃 、 氯仿 为溶剂， 反应 5.0h， 生成 (S)-methyl (5-(4-(3-methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate mesylate
  参考文献：
  名称：

  PYRROLO[2,1-F][1,2,4]TRIAZINE COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF

  摘要：

  本发明涉及一种吡咯并[2,1-f][1,2,4]三嗪化合物，其异构体或药学上可接受的盐、酯或水合物，以及其制备方法和应用。吡咯并[2,1-f][1,2,4]三嗪化合物具有一般式(I)表示的结构。一般式(I)表示的吡咯并[2,1-f][1,2,4]三嗪化合物可以抑制磷脂酰肌醇-3激酶（PI3K）信号通路，因此可用于制备用于治疗磷脂酰肌醇-3激酶相关疾病如癌症的药物。

  公开号：

  US20150141644A1
• 作为产物：
  描述：

  methyl 1-amino-5-carbamoyl-1H-pyrrole-3-carboxylate 在 4-二甲氨基吡啶 、 copper(II) choride dihydrate 、 dimethyl sulfide borane 、 potassium carbonate 、 sodium hydroxide 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.5h， 生成 (S)-5-(4-(3-methylmorpholino)-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine
  参考文献：
  名称：

  Identification of methyl (5-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-4-morpholinopyrrolo[2,1-f][1,2,4]triazin-2-yl)-4-(trifluoromethyl)pyridin-2-yl)carbamate (CYH33) as an orally bioavailable, highly potent, PI3K alpha inhibitor for the treatment of advanced solid tumors

  摘要：

  In various human cancers, PI3Ks pathway is ubiquitously dysregulated and thus become a promising anti-cancer target. To discover new potent and selective PI3K inhibitors as potential anticancer drugs, new pyrrolo[2,1-f][1,2,4]triazines were designed, leading to the discovery of compound 37 (CYH33), a selective PI3Kα inhibitor (IC₅₀ = 5.9 nM, β/α, δ/α,γ/α = 101-, 13-, 38-fold). Western blot analysis confirmed that compound 37 could inhibit phosphorylation of AKT in human cancer cells to modulate the cellular PI3K/AKT/mTOR pathway. And further evaluation in vivo against SKOV-3 xenograft models demonstrated that a dose-dependent antitumor efficacy was achieved.

  DOI：

  10.1016/j.ejmech.2020.112913

文献信息

• Pyrrolo[2,1-f][1,2,4]triazine compound, and preparation method and application thereof
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：US09447101B2

  公开（公告）日：2016-09-20

  The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.

  本发明涉及一种吡咯并[2,1-f][1,2,4]三嗪化合物、其异构体或其药学上可接受的盐、酯或水合物，以及其制备方法和应用。该吡咯并[2,1-f][1,2,4]三嗪化合物具有通式(I)所表示的结构。通式(I)所表示的吡咯并[2,1-f][1,2,4]三嗪化合物能够抑制磷脂酰肌醇-3激酶（PI3K）信号通路，因此可用于制备治疗磷脂酰肌醇-3激酶相关疾病如癌症的药物。
• PYRROLO[2,1-F[1,2,4]TRIAZINE COMPOUNDS, PREPARATION METHODS AND APPLICATIONS THEREOF
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：US20170000800A1

  公开（公告）日：2017-01-05

  The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.
• US9447101B2
  申请人：——

  公开号：US9447101B2

  公开（公告）日：2016-09-20
• US9724352B2
  申请人：——

  公开号：US9724352B2

  公开（公告）日：2017-08-08
• PYRROLO[2,1-F][1,2,4]TRIAZINE COMPOUND, AND PREPARATION METHOD AND APPLICATION THEREOF
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：US20150141644A1

  公开（公告）日：2015-05-21

  The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.

  本发明涉及一种吡咯并[2,1-f][1,2,4]三嗪化合物，其异构体或药学上可接受的盐、酯或水合物，以及其制备方法和应用。吡咯并[2,1-f][1,2,4]三嗪化合物具有一般式(I)表示的结构。一般式(I)表示的吡咯并[2,1-f][1,2,4]三嗪化合物可以抑制磷脂酰肌醇-3激酶（PI3K）信号通路，因此可用于制备用于治疗磷脂酰肌醇-3激酶相关疾病如癌症的药物。