N-(7-acetyl-5-cyano-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)acetamide

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(7-acetyl-5-cyano-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)acetamide
• 英文别名: N-(7-Acetyl-5-cyano-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-D]pyrimidin-2-YL)acetamide；N-(7-acetyl-5-cyano-4-oxo-3H-pyrrolo[2,3-d]pyrimidin-2-yl)acetamide
• 化学式: C₁₁H₉N₅O₃
• 分子量: 259.224
• InChiKey: QUPHWKNIQAJWLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-(7-acetyl-5-cyano-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)acetamide 在 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 6.0h， 生成 2-氨基-4-氯-7h-吡咯并[2,3-d]嘧啶-5-甲腈
  参考文献：
  名称：

  Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Biomarkers

  摘要：

  IKK beta plays a central role in the canonical NF-kB pathway, which has been extensively characterized. The role of IKK alpha in the noncanonical NF-kB pathway, and indeed in the canonical pathway as a complex with IKK beta, is less well understood. One major reason for this is the absence of chemical tools designed as selective inhibitors for IKK alpha over IKK beta. Herein, we report for the first time a series of novel, potent, and selective inhibitors of IKK alpha. We demonstrate effective target engagement and selectivity with IKK alpha in U2OS cells through inhibition of IKK alpha-driven p100 phosphorylation in the noncanonical NF-kB pathway without affecting IKK beta-dependent IKapp-B alpha loss in the canonical pathway. These compounds represent the first chemical tools that can be used to further characterize the role of IKK alpha a in cellular signaling, to dissect this from IKK beta and to validate it in its own right as a target in inflammatory diseases.

  DOI：

  10.1021/acs.jmedchem.7b00484
• 作为产物：
  描述：

  乙酸酐 、 2-氨基-4-氧代-4,7-二氢-3H-吡咯并[2,3-D]嘧啶-5-甲腈 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 3.0h， 以86%的产率得到N-(7-acetyl-5-cyano-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-2-yl)acetamide
  参考文献：
  名称：

  实用的合成古菌碱及其基础

  摘要：

  一种实用的合成路线至7-亚胺甲基氨-7-脱氮（archaeosine），在古细菌的tRNA中观察到的hypermodified核苷，已经被开发出来，其中包括加入羟胺至氰基-7-氰基-7-脱氮的（PREQ 0 -核苷）和随后的Pd催化的氢化反应。从Hocek等人开发的优化的β-选择性糖基化获得PreQ 0-核苷。随后从其前体7-氰基-7-脱氮鸟嘌呤（preQ 0）以高收率合成相应的古植物碱。

  DOI：

  10.1016/j.tet.2018.08.003

文献信息

• The synthesis of 7-deazaguanines as potential inhibitors of guanosine triphosphate cyclohydrolase I
  作者：Colin L Gibson、Salvatore La Rosa、Kyuji Ohta、Peter H Boyle、Fabien Leurquin、Alexandra Lemaçon、Colin J Suckling

  DOI：10.1016/j.tet.2003.11.030

  日期：2004.1

  compounds can be prepared. These methods supplement our previous work that established routes for the synthesis of 7- and 8-substituted 7-deazaguanines. Emphasis is placed on the properties of 2-thioalkyl pyrimidines as intermediates because they provide the basis for a traceless solid-state synthesis of purines, pteridines, and their analogues. Compounds prepared have been assessed in a primary screen for

  作为GTP环水解酶I（生物合成途径中导致二氢叶酸和四氢生物蝶呤的第一个酶）的抑制剂，各种取代的7-脱氮鸟嘌呤是令人感兴趣的。描述了合成在2、6和9位（嘌呤编号）取代的7-脱氮鸟嘌呤的方法，从而可以制备各种各样的化合物。这些方法补充了我们先前的工作，该工作为合成7和8位取代的7-脱氮鸟嘌呤建立了途径。重点放在2-硫代烷基嘧啶作为中间体的性质上，因为它们为嘌呤，蝶啶及其类似物的无痕固态合成提供了基础。已经在初步筛选中评估了制备的化合物抑制GTPCH I的能力，并且已证明8-甲基脱氮鸟嘌呤比尚未描述的任何抑制剂都具有更强的效力。几种化合物似乎已通过GTPCH I进行了转化。借助于模型反应，它们的行为可以在GTPCH I的水解相机理的背景下进行解释。
• Inhibitory Kappa B Kinase α (IKKα) Inhibitors That Recapitulate Their Selectivity in Cells against Isoform-Related Biomarkers
  作者：Nahoum G. Anthony、Jessica Baiget、Giacomo Berretta、Marie Boyd、David Breen、Joanne Edwards、Carly Gamble、Alexander I. Gray、Alan L. Harvey、Sophia Hatziieremia、Ka Ho Ho、Judith K. Huggan、Stuart Lang、Sabin Llona-Minguez、Jia Lin Luo、Kathryn McIntosh、Andrew Paul、Robin J. Plevin、Murray N. Robertson、Rebecca Scott、Colin J. Suckling、Oliver B. Sutcliffe、Louise C. Young、Simon P. Mackay

  DOI：10.1021/acs.jmedchem.7b00484

  日期：2017.8.24

  IKK beta plays a central role in the canonical NF-kB pathway, which has been extensively characterized. The role of IKK alpha in the noncanonical NF-kB pathway, and indeed in the canonical pathway as a complex with IKK beta, is less well understood. One major reason for this is the absence of chemical tools designed as selective inhibitors for IKK alpha over IKK beta. Herein, we report for the first time a series of novel, potent, and selective inhibitors of IKK alpha. We demonstrate effective target engagement and selectivity with IKK alpha in U2OS cells through inhibition of IKK alpha-driven p100 phosphorylation in the noncanonical NF-kB pathway without affecting IKK beta-dependent IKapp-B alpha loss in the canonical pathway. These compounds represent the first chemical tools that can be used to further characterize the role of IKK alpha a in cellular signaling, to dissect this from IKK beta and to validate it in its own right as a target in inflammatory diseases.
• A practical synthesis of archaeosine and its base
  作者：Natsuhisa Oka、Akane Fukuta、Kaori Ando

  DOI：10.1016/j.tet.2018.08.003

  日期：2018.9

  A practical synthetic route to 7-formamidino-7-deazaguanosine (archaeosine), a hypermodified nucleoside observed in archaeal tRNA, has been developed, which involves the addition of hydroxylamine to the cyano group of 7-cyano-7-deazaguanosine (preQ0-nucleoside) and a subsequent Pd-catalyzed hydrogenation. PreQ0-nucleoside was obtained from an optimized β-selective glycosylation developed by Hocek et al

  一种实用的合成路线至7-亚胺甲基氨-7-脱氮（archaeosine），在古细菌的tRNA中观察到的hypermodified核苷，已经被开发出来，其中包括加入羟胺至氰基-7-氰基-7-脱氮的（PREQ 0 -核苷）和随后的Pd催化的氢化反应。从Hocek等人开发的优化的β-选择性糖基化获得PreQ 0-核苷。随后从其前体7-氰基-7-脱氮鸟嘌呤（preQ 0）以高收率合成相应的古植物碱。