4-chloro-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid tert-butyl ester | 1351094-00-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid tert-butyl ester
• 英文别名: 1,1-dimethylethyl 4-chloro-1H-pyrrolo[2,3-d]pyrimidine-6-carboxylate；tert-Butyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate；tert-butyl 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylate
• CAS: 1351094-00-2
• 化学式: C₁₁H₁₂ClN₃O₂
• 分子量: 253.688
• InChiKey: ZRISKYMQDIAOHD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 在 四(三苯基膦)钯 、 potassium carbonate 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 4-{4-[(4-tert-butylbenzoylamino)methyl]-3-fluorophenyl}-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (2-dimethylaminoethyl)amide
  参考文献：
  名称：

  [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE
  [FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON

  摘要：

  公开号：

  WO2014064131A3
• 作为产物：
  描述：

  甘氨酸叔丁酯 在 sodium hydride 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 24.0h， 生成 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid tert-butyl ester
  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

文献信息

• [EN] COMPOUNDS AND METHODS<br/>[FR] COMPOSÉS ET PROCÉDÉS
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011149827A1

  公开（公告）日：2011-12-01

  Disclosed are compounds having the Formula (I), wherein X, Y, Z, R1, R2 and R3 are as defined herein, and methods of making and using the same.

  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。
• INHIBITORS OF BRUTON'S TYROSINE KINASE
  申请人：HOFFMANN-LA ROCHE INC.

  公开号：US20150284394A1

  公开（公告）日：2015-10-08

  This application discloses compounds according to generic Formula I wherein all variables 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 Formula I and at least one carrier, diluent or excipient.

  该申请公开了符合通用式I的化合物，其中所有变量的定义如本文所述，这些化合物可以抑制Btk。本文所披露的化合物有助于调节Btk的活性并治疗与过度Btk活性相关的疾病。这些化合物还有助于治疗与异常B细胞增殖相关的炎症和自身免疫性疾病，如类风湿性关节炎。同时公开了含有通用式I化合物和至少一种载体、稀释剂或赋形剂的组合物。
• [EN] INHIBITORS OF BRUTON'S TYROSINE KINASE<br/>[FR] INHIBITEURS DE LA TYROSINE KINASE DE BRUTON
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014064131A3

  公开（公告）日：2014-10-16
• Identification of Purines and 7-Deazapurines as Potent and Selective Type I Inhibitors of Troponin I-Interacting Kinase (TNNI3K)
  作者：Brian G. Lawhorn、Joanne Philp、Yongdong Zhao、Christopher Louer、Marlys Hammond、Mui Cheung、Harvey Fries、Alan P. Graves、Lisa Shewchuk、Liping Wang、Joshua E. Cottom、Hongwei Qi、Huizhen Zhao、Rachel Totoritis、Guofeng Zhang、Benjamin Schwartz、Hu Li、Sharon Sweitzer、Dennis A. Holt、Gregory J. Gatto、Lara S. Kallander

  DOI：10.1021/acs.jmedchem.5b00931

  日期：2015.9.24

  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.