6-((4-chloro-1,3,5-triazine-2-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazine-3(4H)-one | 1373771-92-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 6-((4-chloro-1,3,5-triazine-2-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazine-3(4H)-one
• 英文别名: 6-[(4-chloro-1,3,5-triazin-2-yl)amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one
• CAS: 1373771-92-6
• 化学式: C₁₂H₁₁ClN₆O₂
• 分子量: 306.711
• InChiKey: KRPIXNCVDZLCRK-UHFFFAOYSA-N

物化性质

• 密度：
  1.466±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-((4-chloro-1,3,5-triazine-2-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazine-3(4H)-one 、 苯酚,4-氨基-2,6-二甲氧基- 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 以65%的产率得到dMe-MT-SYK-03
  参考文献：
  名称：

  Modeling comparative selectivity profiles of kinase inhibitors using FEP/MD protocol

  摘要：

  Free energy perturbation (FEP)-based molecular modeling simulation of 5-fluoropyrimidine and 1,3,5-triazine derivatives followed by their synthesis and experimental evaluation have been carried out to estimate kinase selectivity profile. 5-Fluoropyrimidine derivatives show similar binding affinity for c-Src, Btk and Jakl kinases, while 1,3,5-triazine derivatives demonstrate c-Src kinase selectivity.

  DOI：

  10.1016/j.mencom.2017.07.009
• 作为产物：
  描述：

  2,4-二氯-1,3,5-三嗪 、 6-氨基-2,2-二甲基-2H-吡啶[3,2-B][1,4]恶嗪-3(4H)-酮 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以80%的产率得到6-((4-chloro-1,3,5-triazine-2-yl)amino)-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazine-3(4H)-one
  参考文献：
  名称：

  Rational design and synthesis of novel Syk-kinase inhibitors

  摘要：

  Molecular modeling and subsequent synthesis of novel Syk-kinase inhibitors, 7H-pyrrolo[2,3-d]pyrimidine and 1,3,5-triazine derivatives, have been carried out. The best of the obtained compounds demonstrated to inhibit Syk-kinase activity at IC50 = 230 +/- 10 nM.

  DOI：

  10.1016/j.mencom.2012.03.006

文献信息

• Crystal salt form of 2,2-dimethyl-6-((4-((3,4,5-trimethoxyphenyl)amino)-1,3,5-triazine-2-yl)amino)-2H-pyrido[3,2-b][1,4]oxazine-3(4H)-one for human use
  申请人：LIMITED “MOLECULAR TECHNOLOGIES”

  公开号：US10745414B2

  公开（公告）日：2020-08-18

  The invention is relevant to chemistry of organic compounds, pharmacology and medicine, and is related to prevention and treatment of musculoskeletal diseases in human and animals associated with the disorder of bone and/or cartilage metabolism, particularly with such musculoskeletal diseases as osteoporosis, osteoarthritis and osteochondrosis, using a new salt form of 2,2-dimethyl-6-((4-((3,4,5-trimethoxyphenyl)amino)-1,3,5-triazine-2-yl)amino)-2H-pyrido[3,2-b][1,4]oxazine-3(4H)-one. A salt of this compound with 4-methylbenzenesulfonic acid including its hydrates, solvates and polymorphic modifications of the salt, hydrates and solvates is featured with acceptable pharmacokinetic parameters and increased efficiency in the inhibition of Src-family kinases and Syk kinase, as well as other therapeutically significant kinases. This invention also covers pharmaceutical compositions containing therapeutically effective amount of the salt according to the invention.

  本发明与有机化合物化学、药理学和医学有关，涉及预防和治疗与骨和/或软骨代谢紊乱有关的人类和动物的肌肉骨骼疾病、特别是骨质疏松症、骨关节炎和骨软化症等肌肉骨骼疾病，使用 2,2-二甲基-6-((4-((3,4,5-三甲氧基苯基)氨基)-1,3,5-三嗪-2-基)氨基)-2H-吡啶并[3,2-b][1,4]恶嗪-3(4H)-酮的新盐形式。该化合物与 4-甲基苯磺酸的盐 包括其水合物、溶解物以及盐、水合物和溶解物的多晶型修饰物，其特点是具有可接受的药代动力学参数，并提高了对 Src 家族激酶和 Syk 激酶以及其他具有治疗意义的激酶的抑制效率。本发明还包括含有治疗有效量的根据本发明的盐的药物组合物。
• NOVEL CRYSTALLINE SALT FORM OF 2,2-DIMETHYL-6-((4-((3,4,5-TRIMETHOXYPHENYL)AMINO)-1,3,5-TRIAZIN-2-YL)AMINO)-2H-PYRIDO[3,2-B][1,4]OXAZIN-3(4H)-ONE FOR MEDICAL APPLICATION
  申请人：Limited "Molecular Technologies"

  公开号：EP3456720B1

  公开（公告）日：2021-06-30
• A NEW CRYSTAL SALT FORM OF 2,2-DIMETHYL-6-((4-((3,4,5-TRIMETHOXYPHENYL)AMINO)-1,3,5-TRIAZINE-2-YL)AMINO)-2H PYRIDO[3,2-B][1,4]OXAZINE-3(4H)-ONE FOR HUMAN USE
  申请人：LIMITED "MOLECULAR TECHNOLOGIES"

  公开号：US20190292198A1

  公开（公告）日：2019-09-26

  The invention is relevant to chemistry of organic compounds, pharmacology and medicine, and is related to prevention and treatment of musculoskeletal diseases in human and animals associated with the disorder of bone and/or cartilage metabolism, particularly with such musculoskeletal diseases as osteoporosis, osteoarthritis and osteochondrosis, using a new salt form of 2,2-dimethyl-6-((4-((3,4,5-trimethoxyphenyl)amino)-1,3,5-triazine-2-yl)amino)-2H-pyrido[3,2-b][1,4]oxazine-3(4H)-one. A salt of this compound with 4-methylbenzenesulfonic acid including its hydrates, solvates and polymorphic modifications of the salt, hydrates and solvates is featured with acceptable pharmacokinetic parameters and increased efficiency in the inhibition of Src-family kinases and Syk kinase, as well as other therapeutically significant kinases. This invention also covers pharmaceutical compositions containing therapeutically effective amount of the salt according to the invention.
• [EN] NOVEL CHEMICAL COMPOUNDS DERIVED FROM 2,4-DIAMINO-1,3,5-TRIAZINE FOR THE PROPHYLAXIS AND TREATMENT OF HUMAN AND ANIMAL DISEASES<br/>[FR] NOUVEAUX COMPOSÉS CHIMIQUES DÉRIVÉS DE 2,4-DIAMINO-1,3,5-TRIAZINE AFIN DE PRÉVENIR ET TRAITER DES MALADIES D'HUMAINS ET D'ANIMAUX<br/>[RU] НОВЫЕ ХИМИЧЕСКИЕ СОЕДИНЕНИЯ ПРОИЗВОДНЫЕ 2,4-ДИАМИНО-1,3,5-ТРИАЗИНА ДЛЯ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ ЗАБОЛЕВАНИЙ ЧЕЛОВЕКА И ЖИВОТНЫХ
  申请人：OBSHCHESTVO S OGRANICHENNOY OTVETSTVENNOSTYU MOLEKULYARNYE T

  公开号：WO2015047124A1

  公开（公告）日：2015-04-02

  Изобретение касается терапии аллергических, аутоиммунных, онкологических и прочих заболеваний с помощью новых семейств химических соединений, обладающих повышенной эффективностью в ингибировании SYK-киназы и ее мутантных форм, а также других терапевтически значимых киназ, повышенной селективностью и биодоступностью.