[4-(8-methylquinazolin-4-yl)piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [4-(8-methylquinazolin-4-yl)piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone
• 英文别名: [4-(8-Methylquinazolin-4-yl)piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone
• 化学式: C₂₂H₂₀F₃N₃O₂
• 分子量: 415.415
• InChiKey: ALRANRPSROSEJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  55.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  8-methyl-4-(1,2,3,6-tetrahydropyridin-4-yl)quinazoline 在 10% palladium hydroxide on charcoal 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、303.99 kPa 条件下， 反应 2.5h， 生成 [4-(8-methylquinazolin-4-yl)piperidin-1-yl]-[4-(trifluoromethoxy)phenyl]methanone
  参考文献：
  名称：

  Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2-d]pyrimidine Based in Vitro Probe BAY-885 for the Kinase ERK5

  摘要：

  The availability of a chemical probe to study the role of a specific domain of a protein in a concentration- and time-dependent manner is of high value. Herein, we report the identification of a highly potent and selective ERK5 inhibitor BAY-885 by high-throughput screening and subsequent structure-based optimization. ERK5 is a key integrator of cellular signal transduction, and it has been shown to play a role in various cellular processes such as proliferation, differentiation, apoptosis, and cell survival. We could demonstrate that inhibition of ERKS kinase and transcriptional activity with a small molecule did not translate into antiproliferative activity in different relevant cell models, which is in contrast to the results obtained by RNAi technology.

  DOI：

  10.1021/acs.jmedchem.8b01606

文献信息

• [EN] IDENTIFICATION AND USE OF ERK5 INHIBITORS<br/>[FR] IDENTIFICATION ET UTILISATION D'INHIBITEURS D'ERK5
  申请人：BAYER AG

  公开号：WO2019170543A1

  公开（公告）日：2019-09-12

  The present invention covers heterocyclic compounds of general formula (I) in which T, U, Y, Z, R1 and R3 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer disorders, as a sole agent or in combination with other active ingredients.

  本发明涵盖了一般式(I)的杂环化合物，其中T、U、Y、Z、R1和R3如本文所定义，制备所述化合物的方法，用于制备所述化合物的中间体化合物，包含所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病，特别是癌症疾病的药物组合物的用途，作为唯一活性成分或与其他活性成分组合使用。
• IDENTIFICATION AND USE OF ERK5 INHIBITORS
  申请人：Bayer Aktiengesellschaft

  公开号：EP3762379A1

  公开（公告）日：2021-01-13
• IDENTIFICATION AND USE OF ERK5 INHIBITOR
  申请人：Bayer Aktiengesellschaft

  公开号：US20210017174A1

  公开（公告）日：2021-01-21

  The present invention covers heterocyclic compounds of general formula (I) in which T, U, Y, Z, R1 and R3 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular of cancer disorders, as a sole agent or in combination with other active ingredients.
• Discovery and Characterization of the Potent and Highly Selective (Piperidin-4-yl)pyrido[3,2-<i>d</i>]pyrimidine Based <i>in Vitro</i> Probe <b>BAY-885</b> for the Kinase ERK5
  作者：Duy Nguyen、Clara Lemos、Lars Wortmann、Knut Eis、Simon J. Holton、Ulf Boemer、Dieter Moosmayer、Uwe Eberspaecher、Joerg Weiske、Christian Lechner、Stefan Prechtl、Detlev Suelzle、Franziska Siegel、Florian Prinz、Ralf Lesche、Barbara Nicke、Katrin Nowak-Reppel、Herbert Himmel、Dominik Mumberg、Franz von Nussbaum、Carl F. Nising、Marcus Bauser、Andrea Haegebarth

  DOI：10.1021/acs.jmedchem.8b01606

  日期：2019.1.24

  The availability of a chemical probe to study the role of a specific domain of a protein in a concentration- and time-dependent manner is of high value. Herein, we report the identification of a highly potent and selective ERK5 inhibitor BAY-885 by high-throughput screening and subsequent structure-based optimization. ERK5 is a key integrator of cellular signal transduction, and it has been shown to play a role in various cellular processes such as proliferation, differentiation, apoptosis, and cell survival. We could demonstrate that inhibition of ERKS kinase and transcriptional activity with a small molecule did not translate into antiproliferative activity in different relevant cell models, which is in contrast to the results obtained by RNAi technology.