N-(3-bromo-2-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-4-cyclopropyl-2-methylbenzamide | 1198765-14-8

• 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: N-(3-bromo-2-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-4-cyclopropyl-2-methylbenzamide
• 英文别名: N-[3-bromo-2-(tert-butyldimethylsilanyloxymethyl)phenyl]-4-cyclopropyl-2-methylbenzamide；N-[3-bromo-2-[[tert-butyl(dimethyl)silyl]oxymethyl]phenyl]-4-cyclopropyl-2-methylbenzamide
• CAS: 1198765-14-8
• 化学式: C₂₄H₃₂BrNO₂Si
• 分子量: 474.513
• InChiKey: VEWRRQHBCWHFQQ-UHFFFAOYSA-N

物化性质

• 沸点：
  474.8±45.0 °C(Predicted)
• 密度：
  1.228±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.41
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(3-bromo-2-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-4-cyclopropyl-2-methylbenzamide 在 2,2,6,6-四甲基哌啶 、 正丁基锂 、 甲基磺酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 2.17h， 生成 2-[3-bromo-2-(tert-butyldimethylsilanyloxymethyl)phenyl]-6-cyclopropyl-2H-isoquinolin-1-one
  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：

  4-溴-2-甲基苯甲酸 在 potassium phosphate 、 氯化亚砜 、 lithium hydroxide monohydrate 、 水 、 palladium diacetate 、 potassium carbonate 、 三环己基膦 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 23.0h， 生成 N-(3-bromo-2-(((tert-butyldimethylsilyl)oxy)methyl)phenyl)-4-cyclopropyl-2-methylbenzamide
  参考文献：
  名称：

  [EN] SUBSTITUTED 1H-PYRROLOPYRIDINONE DERIVATIVES AS KINASE INHIBITORS
  [FR] DÉRIVÉS DE 1H-PYRROLOPYRIDINONE SUBSTITUÉS EN TANT QU'INHIBITEURS DE KINASE

  摘要：

  公开号：

  WO2014125408A3

文献信息

• Inhibitors of Bruton's Tyrosine Kinase
  申请人：Berthel Steven

  公开号：US20100222325A1

  公开（公告）日：2010-09-02

  This application discloses 5-phenyl-1H-pyridin-2-one, 6-phenyl-2H-pyridazin-3-one, and 5-Phenyl-1H-pyrazin-2-one derivatives according to generic Formulae I-III: wherein, variables Q, R, X, X′, Y 1 , Y 2 , Y 2′ , Y 3 , Y 4 , Y 5 , m, and n are defined 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 Formulae I-III and at least one carrier, diluent or excipient.

  该应用程序根据通用公式I-III披露了5-苯基-1H-吡啶-2-酮，6-苯基-2H-吡啶-3-酮和5-苯基-1H-吡嗪-2-酮衍生物： 其中，变量Q、R、X、X'、Y1、Y2、Y2'、Y3、Y4、Y5、m和n的定义如本文所述，这些化合物抑制Btk。本文披露的化合物对调节Btk的活性并治疗与过度Btk活性相关的疾病有用。这些化合物进一步有助于治疗与异常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。还披露了含有公式I-III化合物和至少一种载体、稀释剂或赋形剂的组合物。
• [EN] ISOQUINOLONES AS BTK INHIBITORS<br/>[FR] UTILISATION D'ISOQUINOLONES COMME INHIBITEURS DE BTK
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2017123695A1

  公开（公告）日：2017-07-20

  The present invention encompasses compounds of the formula (I) wherein the groups R1, R2, R3, R4 and R5 are defined herein, which are suitable for the treatment of diseases related to Bruton's tyrosine kinase (BTK), and processes for making these compounds, pharmaceutical preparations containing these compounds, and their methods of use.

  本发明涵盖了式(I)化合物，其中R1、R2、R3、R4和R5基团如本文所定义，适用于治疗与布鲁顿氨基酸激酶（BTK）相关的疾病，以及制备这些化合物的过程、含有这些化合物的药物制剂，以及它们的使用方法。
• [EN] SUBSTITUTED 1H-PYRROLOPYRIDINONE DERIVATIVES AS KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE 1H-PYRROLOPYRIDINONE SUBSTITUÉS EN TANT QU'INHIBITEURS DE KINASE
  申请人：AURIGENE DISCOVERY TECH LTD

  公开号：WO2014125408A3

  公开（公告）日：2014-12-18
• Structure-Based Drug Design of RN486, a Potent and Selective Bruton’s Tyrosine Kinase (BTK) Inhibitor, for the Treatment of Rheumatoid Arthritis
  作者：Yan Lou、Xiaochun Han、Andreas Kuglstatter、Rama K. Kondru、Zachary K. Sweeney、Michael Soth、Joel McIntosh、Renee Litman、Judy Suh、Buelent Kocer、Dana Davis、Jaehyeon Park、Sandra Frauchiger、Nolan Dewdney、Hasim Zecic、Joshua P. Taygerly、Keshab Sarma、Junbae Hong、Ronald J. Hill、Tobias Gabriel、David M. Goldstein、Timothy D. Owens

  DOI：10.1021/jm500305p

  日期：2015.1.8

  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.