1,1-dimethylethyl 5-bromo-4-[(3-{[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)amino]sulfonyl}phenyl)amino]-7H-pyrrolo[2,3-d]pyrimidine-7-carboxylate | 1351094-63-7

• 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: 1,1-dimethylethyl 5-bromo-4-[(3-{[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)amino]sulfonyl}phenyl)amino]-7H-pyrrolo[2,3-d]pyrimidine-7-carboxylate
• 英文别名: Tert-butyl 5-bromo-4-[3-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]sulfamoyl]anilino]pyrrolo[2,3-d]pyrimidine-7-carboxylate
• CAS: 1351094-63-7
• 化学式: C₂₃H₂₈BrN₅O₆S
• 分子量: 582.475
• InChiKey: FXZLUPLOBCFNPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  141
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl 5-bromo-4-[(3-{[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)amino]sulfonyl}phenyl)amino]-7H-pyrrolo[2,3-d]pyrimidine-7-carboxylate 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 palladium on activated charcoal 盐酸 、 氢气 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 乙腈 为溶剂， 反应 16.25h， 生成 N-methyl-3-{[5-(1-methylethyl)-1H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzenesulfonamide hydrochloride
  参考文献：
  名称：

  [EN] COMPOUNDS AND METHODS
  [FR] COMPOSÉS ET PROCÉDÉS

  摘要：

  揭示了具有化学式（I）的化合物，其中X、Y、Z、R1、R2和R3如本文所定义，并公开了制备和使用这些化合物的方法。

  公开号：

  WO2011149827A1
• 作为产物：
  描述：

  5-溴-4-氯-7H-吡咯并[2,3-d]嘧啶 在 4-二甲氨基吡啶 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 0.25h， 生成 1,1-dimethylethyl 5-bromo-4-[(3-{[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)amino]sulfonyl}phenyl)amino]-7H-pyrrolo[2,3-d]pyrimidine-7-carboxylate
  参考文献：
  名称：

  Identification of Purines and 7-Deazapurines as Potent and Selective Type I Inhibitors of Troponin I-Interacting Kinase (TNNI3K)

  摘要：

  A series of cardiac troponin I-interacting kinase (TNNI3K) inhibitors arising from 34(9H-purin-6-yl)amino)-N-methyl-benzenesulfonamide (1) is disclosed along with fundamental structure function relationships that delineate the role of each element of 1 for TNNI3K recognition. An X-ray structure of 1 bound to TNNI3K confirmed its Type I binding mode and is used to rationalize the structure activity relationship and employed to design potent, selective, and orally bioavailable TNNI3K inhibitors. Identification of the 7-deazapurine heterocycle as a superior template (vs purine) and its elaboration by introduction of C4-benzenesulfonamide and C7- and C8-7-deazapurine substituents produced compounds with substantial improvements in potency (>1000-fold), general kinase selectivity (10-fold improvement), and pharmacokinetic properties (>10-fold increase in poDNAUC). Optimal members of the series have properties suitable for use in in vitro and in vivo experiments aimed at elucidating the role of TNNI3K in cardiac biology and serve as leads for developing novel heart failure medicines.

  DOI：

  10.1021/acs.jmedchem.5b00931