4-((7-(cyclohexylmethoxy)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)amino)benzenesulfonamide | 1606157-60-1

• 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: 4-((7-(cyclohexylmethoxy)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-yl)amino)benzenesulfonamide
• 英文别名: 4-[[7-(cyclohexylmethoxy)-2H-triazolo[4,5-d]pyrimidin-5-yl]amino]benzenesulfonamide
• CAS: 1606157-60-1
• 化学式: C₁₇H₂₁N₇O₃S
• 分子量: 403.465
• InChiKey: HQGOXGMCHYWWCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  157
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  7-(cyclohexylmethoxy)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine 在 氯化亚砜 、 三氟乙酸 、 lithium chloride 、 亚硝酸异戊酯 作用下， 以 2,2,2-三氟乙醇 、 N,N-二甲基乙酰胺 为溶剂， 反应 19.0h， 生成 4-((7-(cyclohexylmethoxy)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-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

文献信息

• Trifluoroacetic Acid in 2,2,2-Trifluoroethanol Facilitates S_NAr Reactions of Heterocycles with Arylamines
  作者：Benoit Carbain、Christopher R. Coxon、Honorine Lebraud、Kristopher J. Elliott、Christopher J. Matheson、Elisa Meschini、Amy R. Roberts、David M. Turner、Christopher Wong、Celine Cano、Roger J. Griffin、Ian R. Hardcastle、Bernard T. Golding

  DOI：10.1002/chem.201304336

  日期：2014.2.17

  explore diverse sets of reaction conditions, and problems with product purification. In contrast, product isolation from TFA‐TFE reactions is straightforward: evaporation of the reaction mixture, basification and chromatography affords analytically pure material. A total of 45 examples are described with seven discrete heterocyclic scaffolds and 2‐, 3‐ and 4‐substituted anilines giving product yields

  小分子药物的发现需要可靠的合成方法，以将氨基化合物连接到杂环支架上。三氟乙酸-2,2,2-三氟乙醇（TFA-TFE）是实现S N的有效组合苯胺与杂环（例如嘌呤和嘧啶）之间的Ar反应被离去基团（氟，氯，溴或烷基磺酰基）取代。该方法提供了多种化合物，这些化合物含有与激酶有效抑制有关的“激酶特权片段”。TFE由于其低亲核性，易于去除和溶解极性底物的能力而成为有利的溶剂。此外，TFE可以通过使离去基团溶剂化来协助Meisenheimer-Jackson中间体的分解。TFA是必要且有效的酸性催化剂，它可以通过N质子化作用活化杂环，而不会通过转化为苯胺类物质而使苯胺失活。TFA-TFE方法与各种官能团兼容，并补充了有机金属替代品，由于试剂的昂贵，经常需要探索各种反应条件以及产物纯化的问题，这通常是不利的。相比之下，从TFA-TFE反应中分离产物非常简单：反应混合物的蒸发，碱化和色谱分离得到分析纯的物质
• 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.