6-氯-4-(环己基甲氧基)-1H-吡唑并[3,4-d]嘧啶 | 1017246-05-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 中文名称: 6-氯-4-(环己基甲氧基)-1H-吡唑并[3,4-d]嘧啶
• 英文名称: 6-chloro-4-(cyclohexylmethoxy)-1H-pyrazolo[3,4-d]pyrimidine
• CAS: 1017246-05-7
• 化学式: C₁₂H₁₅ClN₄O
• mdl: MFCD25748164
• 分子量: 266.73
• InChiKey: RSUAPEJWBFNULK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.583
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-氯-4-(环己基甲氧基)-1H-吡唑并[3,4-d]嘧啶 、 磺胺 在 三氟乙酸 作用下， 以 2,2,2-三氟乙醇 为溶剂， 以28%的产率得到4-((4-(cyclohexylmethoxy)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)benzenesulfonamide
  参考文献：
  名称：

  Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines

  摘要：

  Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 44(6-([1,1'-bipheny1]-3-y1)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0.044 mu M) but was similar to 2000-fold less active toward CDK1 (IC50 86 mu M). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2.

  DOI：

  10.1021/acs.jmedchem.6b01254
• 作为产物：
  描述：

  4-(cyclohexylmethoxy)-1H-pyrazolo[3,4-d]pyrimidin-6-amine 在 氯化亚砜 、 lithium chloride 、 亚硝酸异戊酯 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 19.0h， 以60%的产率得到6-氯-4-(环己基甲氧基)-1H-吡唑并[3,4-d]嘧啶
  参考文献：
  名称：

  Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines

  摘要：

  Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 44(6-([1,1'-bipheny1]-3-y1)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0.044 mu M) but was similar to 2000-fold less active toward CDK1 (IC50 86 mu M). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2.

  DOI：

  10.1021/acs.jmedchem.6b01254

文献信息

• WO2008/39359
  申请人：——

  公开号：——

  公开（公告）日：——
• BICYCLIC PYRIMIDINE KINASE INHIBITORS
  申请人：Connolly Peter J.

  公开号：US20090076037A1

  公开（公告）日：2009-03-19

  The present invention is directed to novel bicyclic pyrimidine compounds of Formula (I) or a form or composition thereof and the use thereof as inhibitors of ATP-protein kinase interactions.
• US8314234B2
  申请人：——

  公开号：US8314234B2

  公开（公告）日：2012-11-20
• [EN] BICYCLIC PYRIMIDINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PYRIMIDINE KINASE BICYCLIQUE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2008039359A2

  公开（公告）日：2008-04-03

  [EN] The present invention is directed to novel bicyclic pyrimidine compounds of Formula (I) or a form or composition thereof, and the use thereof as inhibitors of ATP-protein kinase interactions.
  [FR] La présente invention concerne des nouveaux composés de pyrimidine bicyclique de formule (I) ou leur forme ou composition, et leur utilisation en tant qu'inhibiteurs d'interactions avec l'ATP-protéine kinase.
• Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines
  作者：Christopher R. Coxon、Elizabeth Anscombe、Suzannah J. Harnor、Mathew P. Martin、Benoit Carbain、Bernard T. Golding、Ian R. Hardcastle、Lisa K. Harlow、Svitlana Korolchuk、Christopher J. Matheson、David R. Newell、Martin E. M. Noble、Mangaleswaran Sivaprakasam、Susan J. Tudhope、David M. Turner、Lan Z. Wang、Stephen R. Wedge、Christopher Wong、Roger J. Griffin、Jane A. Endicott、Céline Cano

  DOI：10.1021/acs.jmedchem.6b01254

  日期：2017.3.9

  Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 44(6-([1,1'-bipheny1]-3-y1)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0.044 mu M) but was similar to 2000-fold less active toward CDK1 (IC50 86 mu M). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2.