2-((叔丁基二甲基甲硅烷基氧基)甲基)-3-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苯胺 | 1147531-06-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-((叔丁基二甲基甲硅烷基氧基)甲基)-3-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苯胺
• 英文名称: 2-(tert-butyldimethylsilanyloxymethyl)-3-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenylamine
• 英文别名: 2-(tert-butyldimethylsilyloxy)methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline；2-(((tert-Butyldimethylsilyl)oxy)methyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline；2-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline
• CAS: 1147531-06-3
• 化学式: C₁₉H₃₄BNO₃Si
• 分子量: 363.38
• InChiKey: RDPWWGOPOPTYHD-UHFFFAOYSA-N

物化性质

• 沸点：
  449.0±40.0 °C(Predicted)
• 密度：
  0.99±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.09
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  53.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  2-((叔丁基二甲基甲硅烷基氧基)甲基)-3-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苯胺 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 N-[2-(tert-butyldimethylsilanyloxymethyl)-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-4-dimethylaminobenzamide
  参考文献：
  名称：

  Structure-Based Drug Design of RN486, a Potent and Selective Bruton’s Tyrosine Kinase (BTK) Inhibitor, for the Treatment of Rheumatoid Arthritis

  摘要：

  Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012, 341, 90), which was selected for advanced preclinical characterization based on its favorable properties.

  DOI：

  10.1021/jm500305p
• 作为产物：
  描述：

  2-溴-6-硝基苯甲醇 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 铁粉 、 氯化铵 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 7.0h， 生成 2-((叔丁基二甲基甲硅烷基氧基)甲基)-3-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苯胺
  参考文献：
  名称：

  Structure-Based Drug Design of RN486, a Potent and Selective Bruton’s Tyrosine Kinase (BTK) Inhibitor, for the Treatment of Rheumatoid Arthritis

  摘要：

  Structure-based drug design was used to guide the optimization of a series of selective BTK inhibitors as potential treatments for Rheumatoid arthritis. Highlights include the introduction of a benzyl alcohol group and a fluorine substitution, each of which resulted in over 10-fold increase in activity. Concurrent optimization of drug-like properties led to compound 1 (RN486) ( J. Pharmacol. Exp. Ther. 2012, 341, 90), which was selected for advanced preclinical characterization based on its favorable properties.

  DOI：

  10.1021/jm500305p

文献信息

• BTK protein kinase inhibitors
  申请人：Dewdney Nolan James

  公开号：US20090105209A1

  公开（公告）日：2009-04-23

  This application discloses pyridine and pyrimidine compounds according to formula I wherein R 1 , R 2 , R 3 , R 4 , R 5 , X 1 and A are as described herein which inhibit Btk. The compounds disclosed herein are useful to modulate the activity of Btk and treat diseases associated with excessive Btk activity. The compounds are further useful to treat inflammatory and auto immune diseases associated with aberrant B-cell proliferation such as rheumatoid arthritis. Also disclosed are compositions containing compounds of formula I and at least one carrier, diluent or excipient.

  这个申请公开了根据公式I的吡啶和嘧啶化合物，其中R1、R2、R3、R4、R5、X1和A如本文所述，可抑制Btk。所公开的化合物有助于调节Btk的活性，并治疗与Btk活性过度相关的疾病。这些化合物进一步用于治疗与异常B细胞增殖相关的炎症和自身免疫疾病，如类风湿性关节炎。还公开了包含公式I化合物和至少一种载体、稀释剂或助剂的组合物。
• [EN] PYRIDINONES/PYRAZINONES, METHOD OF MAKING, AND METHOD OF USE THEREOF<br/>[FR] PYRIDINONES/PYRAZINONES, LEUR PROCÉDÉ DE FABRICATION ET LEUR MÉTHODE D'UTILISATION
  申请人：GILEAD CONNECTICUT INC

  公开号：WO2012031004A1

  公开（公告）日：2012-03-08

  Pyridone and pyrazinone compounds of Formula (I) including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  Formula (I)中的吡啶酮和吡嗪酮化合物，包括其立体异构体、互变异构体和药学上可接受的盐，用于抑制Btk激酶，并用于治疗由Btk激酶介导的炎症等免疫紊乱。公开了使用Formula I化合物进行哺乳动物细胞中的体外、体内和体内诊断以及治疗此类疾病或相关病理条件的方法。
• PYRIDINONES/PYRAZINONES, METHOD OF MAKING, AND METHOD OF USE THEREOF
  申请人：Currie Kevin S.

  公开号：US20130281432A1

  公开（公告）日：2013-10-24

  Pyridone and pyrazinone compounds of Formula I including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  本发明涉及公式I的吡啶酮和吡嗪酮化合物，包括立体异构体，互变异构体以及其药物可接受的盐。这些化合物对于抑制Btk激酶以及治疗由Btk激酶介导的免疫性疾病，如炎症，具有用途。本发明还公开了使用公式I化合物进行体外、原位和体内诊断和治疗哺乳动物细胞中的这些疾病或相关病理条件的方法。
• PRIMARY CARBOXAMIDES AS BTK INHIBITORS
  申请人：ABBVIE INC.

  公开号：US20150005279A1

  公开（公告）日：2015-01-01

  The invention provides compounds 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，其可以是药物可接受的盐、前药、生物活性代谢物、立体异构体和同分异构体，其中变量在此定义。该发明的化合物可用于治疗免疫和肿瘤病症。
• Pyridinones/pyrazinones, method of making, and method of use thereof
  申请人：Currie Kevin S.

  公开号：US09249123B2

  公开（公告）日：2016-02-02

  Pyridone and pyrazinone compounds of Formula I including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  本发明涉及公式I的吡啶酮和吡嗪酮化合物，包括立体异构体，互变异构体和其药学上可接受的盐，用于抑制Btk激酶，并用于治疗由Btk激酶介导的炎症等免疫性疾病。还揭示了使用公式I化合物在哺乳动物细胞中进行体外，体内和原位诊断和治疗此类疾病或相关病理条件的方法。