2-amino-4-((1R,2S,3R,4S)-2,3,4-trihydroxycyclopentylamino)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile | 1643690-47-4

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 2-amino-4-((1R,2S,3R,4S)-2,3,4-trihydroxycyclopentylamino)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• 英文别名: 2-amino-4-[[(1R,2S,3R,4S)-2,3,4-trihydroxycyclopentyl]amino]-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
• CAS: 1643690-47-4
• 化学式: C₁₂H₁₄N₆O₃
• 分子量: 290.282
• InChiKey: FDLNIALCQCFXKJ-CRYJXSNHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  164
• 氢给体数：
  6
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  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 、 苄基三乙基氯化铵 、 N,N-二甲基苯胺 、 三乙胺 、 三氯氧磷 作用下， 以 乙腈 、 正丁醇 为溶剂， 反应 39.0h， 生成 2-amino-4-((1R,2S,3R,4S)-2,3,4-trihydroxycyclopentylamino)-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile
  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

文献信息

• Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)
  作者：Sabin Llona-Minguez、Simon P Mackay

  DOI：10.3762/bjoc.10.135

  日期：——

  A convergent and stereoselective synthesis of chiral cyclopentyl- and cyclohexylamine derivatives of nucleoside Q precursor (PreQ0) has been accomplished. This synthetic route allows for an efficient preparation of 4-substituted analogues with interesting three-dimensional character, including chiral cyclopentane-1,2-diol and -1,2,3-triol derivatives. This unusual substitution pattern provides a useful

  已经完成了核苷 Q 前体 (PreQ0) 的手性环戊基和环己胺衍生物的收敛和立体选择性合成。这种合成路线允许有效制备具有有趣的三维特征的 4 取代类似物，包括手性 cyclopentane-1,2-diol 和 -1,2,3-triol 衍生物。这种不寻常的取代模式为发现新的生物活性分子提供了一个有用的起点。