6-溴-4-氯-7H-吡咯并嘧啶 | 784150-41-0

• 物质功能分类: 医药中间体 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 中文名称: 6-溴-4-氯-7H-吡咯并嘧啶
• 中文别名: 6-溴-4-氯-7H-吡咯并[2,3-d]嘧啶
• 英文名称: 6-bromo-4-chloro-7H-pyrrolo[2,3-d]pyrimidine
• CAS: 784150-41-0
• 化学式: C₆H₃BrClN₃
• 分子量: 232.467
• InChiKey: NJPXMLQSSKQIJH-UHFFFAOYSA-N

物化性质

• 密度：
  1.996±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  6-溴-4-氯-7H-吡咯并嘧啶 在 silver trifluoromethanesulfonate 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 N-methyl-3-{[6-(3-methylphenyl)-1H-pyrrolo[2,3-d]pyrimidin-4-yl]amino}benzenesulfonamide
  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
• 作为产物：
  描述：

  4-氯-7-(苯基磺酰基)-7h-吡咯并[2,3-d]嘧啶 在 1,2-二溴四氯乙烷 、 potassium tert-butylate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 6-溴-4-氯-7H-吡咯并嘧啶
  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

• Heterocyclic Compounds Useful as RAF Kinase Inhibitors
  申请人：Cossrow Jennifer

  公开号：US20090005359A1

  公开（公告）日：2009-01-01

  The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.

  本发明提供了作为Raf蛋白激酶抑制剂有用的化合物。本发明还提供了这些化合物的组合物，以及治疗Raf介导疾病的方法。
• [EN] PIPERIDINE DERIVATIVES AS INHIBITORS OF UBIQUITIN SPECIFIC PROTEASE 7<br/>[FR] DÉRIVÉS DE PIPÉRIDINE UTILISÉS COMME INHIBITEURS DE LA PROTÉASE SPÉCIFIQUE DE L'UBIQUITINE 7
  申请人：ALMAC DISCOVERY LTD

  公开号：WO2018073602A1

  公开（公告）日：2018-04-26

  The present invention concerns the identification of inhibitors of ubiquitin specific protease 7 (USP7), and methods of use thereof.

  这项发明涉及抑制泛素特异性蛋白酶7（USP7）的识别，以及其使用方法。
• [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。
• [EN] BIARYL COMPOUNDS USEFUL FOR THE TREATMENT OF HUMAN DISEASES IN ONCOLOGY, NEUROLOGY AND IMMUNOLOGY<br/>[FR] COMPOSÉS BIARYLIQUES UTILES POUR LE TRAITEMENT DE MALADIES HUMAINES EN ONCOLOGIE, NEUROLOGIE ET IMMUNOLOGIE
  申请人：BIOGEN IDEC INC

  公开号：WO2015089327A1

  公开（公告）日：2015-06-18

  The present invention provides compounds and compositions thereof which are useful as inhibitors of Bruton's tyrosine kinase and which exhibit desirable characteristics for the same.

  本发明提供了作为Bruton's酪氨酸激酶抑制剂的化合物及其组合物，具有适用于同一目的的理想特性。
• Modification of Pyrrolo[2,3-<i>d</i>]pyrimidines by C-H Borylation Followed by Cross-Coupling or Other Transformations: Synthesis of 6,8-Disubstituted 7-Deazapurine Bases
  作者：Martin Klečka、Lenka Poštová Slavětínská、Michal Hocek

  DOI：10.1002/ejoc.201501177

  日期：2015.12

  6-arylpyrrolo[2,3-d]pyrimidine (6-substituted 8-aryl-7-deazapurine derivatives) was developed based on iridium-catalyzed C–H borylations of pyrrolo[2,3-d]pyrimidines at the 6-position followed by the Suzuki cross-coupling reactions or other functional group transformations of the boronates. Biologically relevant 6-arylpyrrolo[2,3-d]pyrimidin-4-amines (8-aryl-7-deazaadenines) and pyrrolo[2,3-d]pyrimidin-4-ones

  基于铱催化的吡咯并[2,3-d]嘧啶（6-取代的8-芳基-7-脱氮杂嘌呤衍生物）的C-H硼化反应，开发了对4-取代的6-芳基吡咯并[2,3-d]嘧啶（6-取代的8-芳基-7-脱氮杂嘌呤衍生物）的一般途径]嘧啶在 6 位，然后是 Suzuki 交叉偶联反应或硼酸盐的其他官能团转化。生物相关的 6-芳基吡咯并[2,3-d]嘧啶-4-胺（8-芳基-7-脱氮杂腺嘌呤）和吡咯并[2,3-d]嘧啶-4-酮（–7-脱氮杂次黄嘌呤）的合成起始于SEM 保护的 4-甲基硫基-或 4-甲氧基吡咯并[2,3-d]嘧啶。在一锅硼酸化/ Suzuki 偶联反应之后进行去甲基化和去保护以产生脱氮杂次黄嘌呤碱，或者通过将硫化物氧化为砜、胺化和去保护以得到去氮杂腺嘌呤。此外，