4-methyl-6-nitro-2,10-dihydro-9-oxa-1,2,4a-triazaphenanthren-3-one | 1613721-72-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-methyl-6-nitro-2,10-dihydro-9-oxa-1,2,4a-triazaphenanthren-3-one
• 英文别名: 4-Methyl-6-nitro-2,10-dihydro-9-oxa-1,2,4a-triaza-phenanthren-3-one；1-methyl-9-nitro-3,5-dihydro-1H-[1,2,4]triazino[3,4-c][1,4]benzoxazin-2-one
• CAS: 1613721-72-4
• 化学式: C₁₁H₁₀N₄O₄
• 分子量: 262.225
• InChiKey: SWJHILGNHUIKHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  99.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-methyl-6-nitro-2,10-dihydro-9-oxa-1,2,4a-triazaphenanthren-3-one 在 tetra-N-butylammonium tribromide 、 氯化铵 、 溶剂黄146 、 锌 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 29.5h， 生成 3-(7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triazaphenanthren-6-ylamino)azetidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of Selective and Orally Bioavailable Protein Kinase Cθ (PKCθ) Inhibitors from a Fragment Hit

  摘要：

  Protein kinase C theta (PKC theta) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKC theta inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.

  DOI：

  10.1021/jm500669m
• 作为产物：
  描述：

  6-硝基-2H-1,4-苯并噁嗪-3(4H)-酮 在 劳森试剂 、 potassium carbonate 、 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 8.5h， 生成 4-methyl-6-nitro-2,10-dihydro-9-oxa-1,2,4a-triazaphenanthren-3-one
  参考文献：
  名称：

  Discovery of Selective and Orally Bioavailable Protein Kinase Cθ (PKCθ) Inhibitors from a Fragment Hit

  摘要：

  Protein kinase C theta (PKC theta) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKC theta inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.

  DOI：

  10.1021/jm500669m

文献信息

• TRIAZINONE COMPOUNDS
  申请人：Wang Jianfei

  公开号：US20140206663A1

  公开（公告）日：2014-07-24

  The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

  本发明提供了一种公式(I)的化合物，其中变量如本文所述定义。所述化合物的药用盐、前药、生物活性代谢物、立体异构体和同分异构体。本发明的化合物可用于治疗免疫学和肿瘤学疾病。
• Substituted 2,10-dihydro-9-oxa-1,2,4A-triazaphenanthren-3-ones and uses thereof
  申请人：George Dawn M.

  公开号：US09115151B2

  公开（公告）日：2015-08-25

  The invention provides a compound of Formula (I) pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.

  本发明提供了公式（I）的化合物，其包括药物可接受的盐、前药、生物活性代谢物、立体异构体和同分异构体，其中所述变量在此定义。本发明的化合物可用于治疗免疫和肿瘤疾病。
• US9115151B2
  申请人：——

  公开号：US9115151B2

  公开（公告）日：2015-08-25
• [EN] TRIAZINONE COMPOUNDS<br/>[FR] COMPOSÉS TRIAZINONES
  申请人：ABBVIE INC

  公开号：WO2014089904A1

  公开（公告）日：2014-06-19

  The invention provides a compound of Formula (I), pharmaceutically acceptable salts, pro-drugs, biologically active metabolites, stereoisomers and isomers thereof wherein the variable are defined herein. The compounds of the invention are useful for treating immunological and oncological conditions.
• Discovery of Selective and Orally Bioavailable Protein Kinase Cθ (PKCθ) Inhibitors from a Fragment Hit
  作者：Dawn M. George、Eric C. Breinlinger、Michael Friedman、Yang Zhang、Jianfei Wang、Maria Argiriadi、Pratima Bansal-Pakala、Martine Barth、David B. Duignan、Prisca Honore、QingYu Lang、Scott Mittelstadt、Dominique Potin、Lian Rundell、Jeremy J. Edmunds

  DOI：10.1021/jm500669m

  日期：2015.1.8

  Protein kinase C theta (PKC theta) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKC theta inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.