2-{[(dimethylamino)methylidene]amino}-3,5-dihydro-7-iodo-3-[(pivaloyloxy)methyl]-4H-pyrrolo[3,2-d]pyrimidin-4-one | 396650-33-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 2-{[(dimethylamino)methylidene]amino}-3,5-dihydro-7-iodo-3-[(pivaloyloxy)methyl]-4H-pyrrolo[3,2-d]pyrimidin-4-one
• 英文别名: 2N-((N,N-dimethylamino)methylidene)-9-iodo-1N-(pivaloyloxy)methyl-9-deazaguanine；[2-(dimethylaminomethylideneamino)-7-iodo-4-oxo-5H-pyrrolo[3,2-d]pyrimidin-3-yl]methyl 2,2-dimethylpropanoate
• CAS: 396650-33-2
• 化学式: C₁₅H₂₀IN₅O₃
• 分子量: 445.26
• InChiKey: ORZDVHSCYHLRQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  90.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-{[(dimethylamino)methylidene]amino}-3,5-dihydro-7-iodo-3-[(pivaloyloxy)methyl]-4H-pyrrolo[3,2-d]pyrimidin-4-one 在 bis-triphenylphosphine-palladium(II) chloride 、 palladium on activated charcoal copper(l) iodide 、 氢气 、 sodium hydride 、 potassium carbonate 、 苯硫酚 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 15.0h， 生成 9-[5',5'-difluoro-5'-(diethylphosphono)pentyl]-2-N-(N,N-dimethylaminomethylidene)-1N-(pivaloyloxy)methyl-9-deazaguanine
  参考文献：
  名称：

  9-脱氮鸟嘌呤衍生物的合成和生物学评估，该衍生物通过接头与二氟亚甲基膦酸连接，作为PNP的多底物类似物抑制剂。

  摘要：

  根据X射线晶体学数据，将9-（5'，5'-二氟-5'-膦戊基）-9-脱氮鸟嘌呤（DFPP-DG）设计为针对嘌呤核苷磷酸化酶（PNP）的多底物类似物抑制剂获得9-（5'，5'-二氟-5'-膦戊基）鸟嘌呤（DFPP-G）与小牛脾PNP的二元复合物。通过9-脱氮-9-碘鸟嘌呤衍生物和ω-炔基二氟亚甲基膦酸酯之间的Sonogashira-偶联反应实现的接头长度调节DFPP-DG及其类似化合物，这是关键反应。DFPP-DG是一种非常有效的PNP抑制剂，与小牛脾脏和人红细胞PNP相比，表观抑制常数（在1 mM磷酸盐存在下）的抑制常数分别为4.4和8.1 nM。它的类似物之一，hom-DFPP-DG，

  DOI：

  10.1016/j.bmcl.2007.05.054
• 作为产物：
  描述：

  2-<<(N,N-Dimethylamino)methylene>amino>-4(3H)-oxo-3-<(pivaloyloxy)methyl>-5H-pyrrolo<3,2-d>pyrimidine 在 N-碘代丁二酰亚胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.17h， 以95%的产率得到2-{[(dimethylamino)methylidene]amino}-3,5-dihydro-7-iodo-3-[(pivaloyloxy)methyl]-4H-pyrrolo[3,2-d]pyrimidin-4-one
  参考文献：
  名称：

  9-卤代9-脱氮鸟嘌呤N 7-（2'-脱氧核糖核苷）的合成

  摘要：

  描述了N 7-糖基化的9-脱氮鸟嘌呤1a以及其9-溴和9-碘衍生物1b，c的合成。区域选择性9-卤化用Ñ溴代琥珀酰亚胺（NBS）和Ñ碘代丁二酰亚胺（NIS）的混合物在所述保护的核碱基完成4A {[（二甲基氨基）亚甲基]氨基} -3,5-二氢-3 - - [（新戊酰氧基（2- ）甲基] -4 H-吡咯并[3,2- d ]嘧啶-4-一）。4a – c的碱基碱基阴离子糖基化与2-deoxy-3,5- di - O-（p -toluoyl）-α-D- erythro-戊呋喃糖基氯（5）提供了受完全保护的中间体6a – c（方案2）。将它们用0.01M NaOMe脱保护，得到糖去保护的衍生物8a – c（方案3）。在较高浓度（0.1M NaOMe）下，新戊酰氧基甲基基团也被除去，得到7a – c，同时浓。水 NH 3溶液提供了核苷1a – c。在D 2 O中，糖的构象总是偏向S（67-61％）。

  DOI：

  10.1002/hlca.200490224

文献信息

• pH-Independent triplex formation: hairpin DNA containing isoguanine or 9-deaza-9-propynylguanine in place of protonated cytosine
  作者：Frank Seela、Khalil I. Shaikh

  DOI：10.1039/b610930f

  日期：——

  (2), 7-bromo-7-deaza-2'-deoxyisoguanosine (2) as well as the propynylated 9-deazaguanine N7-(2'-deoxyribonucleoside) were prepared. For this the phosphoramidites 9a, b of the nucleoside 1 and, the phosphoramidites 19, 20 of compound 3b were synthesized. They were employed in solid-phase oligonucleotide synthesis to yield the protected 31-mer oligonucleotides. The deblocking of the allyl-protected oligonucleotides

  制备了包含2'-脱氧异鸟苷（2），7-溴-7-脱氮基2'-脱氧异鸟苷（2）以及丙烯酰化的9-脱氮鸟嘌呤N7-（2'-脱氧核糖核苷）的三链体形成寡核苷酸（TFO）。为此，合成了核苷1的亚磷酰胺9a，b以及化合物3b的亚磷酰胺19、20。它们被用于固相寡核苷酸合成中以产生受保护的31聚体寡核苷酸。通过Pd（0）[PPh3] 4-PPh3，然后用25％aq。水溶液进行含1的烯丙基保护的寡核苷酸的解封闭。NH3。通过紫外熔融曲线分析研究了31聚体单链分子内三链体的形成。在单链31-mer寡核苷酸中，dCH（+）-dG-dC基础三联体中的质子化dC被2'-脱氧异鸟苷（1），7-bromo-7-deaza-2'取代 -deoxyisoguanosine（2）和9-deaza-9-propynylguanine N7-（2'-deoxyribonucleoside）（3b）。用化合物1和3b取代质子化的
• NANOPARTICLE NUCLEIC ACID BINDING COMPOUND CONJUGATES FORMING I-MOTIFS
  申请人：Seela Frank

  公开号：US20100290992A1

  公开（公告）日：2010-11-18

  The present invention concerns the field of nanoparticle bioconjugates which form an i-motif or an i-motif related structure (compositions) without or with at least one further nucleic acid binding compound. The i-motif base pairs can be charged or non-charged. Their assembly can be controlled by the pH value or temperature. At least one of these nucleic acid binding compounds has to be attached at least to a nanoparticle. The methods provide compositions used for DNA driven programmable nanoparticle assemblies, electronic circuits, diagnostic detection tools, biosensors, memory storage devices, diagnostic devices for biomolecule sequencing and detection, drug delivery, application in tumour diagnostics and treatment, nanomachines, nanofabrication, nanocatalysis, nanoarrays, and nanoscaled enzyme reactors.

  本发明涉及纳米颗粒生物共轭物的领域，其形成了一个i-结构或与i-结构相关的结构（组成物），没有或至少有一种进一步的核酸结合化合物。i-结构碱基对可以带电或不带电。它们的组装可以通过pH值或温度进行控制。这些核酸结合化合物中至少有一种必须至少附着在一个纳米颗粒上。该方法提供了用于DNA驱动的可编程纳米颗粒组装、电子电路、诊断检测工具、生物传感器、存储器设备、用于生物分子测序和检测的诊断设备、药物传递、应用于肿瘤诊断和治疗、纳米机器、纳米制造、纳米催化、纳米阵列和纳米级酶反应器的组成物。
• Structural-based design and synthesis of novel 9-deazaguanine derivatives having a phosphate mimic as multi-substrate analogue inhibitors for mammalian PNPs
  作者：Sadao Hikishima、Mariko Hashimoto、Lucyna Magnowska、Agnieszka Bzowska、Tsutomu Yokomatsu

  DOI：10.1016/j.bmc.2010.01.062

  日期：2010.3

  9-(5',5'-Difluoro-5'-phosphonopentyl)-9-deazaguanine (DFPP-DG) was designed as a multi-substrate analogue inhibitor against purine nucleoside phosphorylase (PNP) on the basis of X-ray crystallographic data obtained for a binary complex of 9-(5',5'-difluoro-5'-phosphonopentyl)guanine (DFPP-G) with calf-spleen PNP. DFPP-DG and its analogous compounds were synthesized by the Sonogashira coupling reaction between a 9-deaza-9-iodoguanine derivative and omega-alkynyldifluoromethylene phosphonates as a key reaction. The experimental details focused on the synthetic chemistry along with some insights into the physical and biological properties of newly synthesized DFPP-DG derivatives are disclosed. (C) 2010 Elsevier Ltd. All rights reserved.
• WO2008/17507
  申请人：——

  公开号：——

  公开（公告）日：——
• Trimeric purine nucleoside phosphorylase: Exploring postulated one-third-of-the-sites binding in the transition state
  作者：Beata Wielgus-Kutrowska、Katarzyna Breer、Mariko Hashimoto、Sadao Hikishima、Tsutomu Yokomatsu、Marta Narczyk、Alicja Dyzma、Agnieszka Girstun、Krzysztof Staroń、Agnieszka Bzowska

  DOI：10.1016/j.bmc.2012.08.045

  日期：2012.11

  Transition-state analogue inhibitors, immucillins, were reported to bind to trimeric purine nucleoside phosphorylase (PNP) with the stoichiometry of one molecule per enzyme trimer [ Miles, R. W.; Tyler, P. C.; Furneaux, R. H.; Bagdassarian, C. K.; Schramm, V. L. Biochem. 1998, 37, 8615]. In attempts to observe and better understand the nature of this phenomenon we have conducted calorimetric titrations of the recombinant calf PNP complexed with immucillin H. However, by striking contrast to the earlier reports, we have not observed negative cooperativity and we got the stoichiometry of three immucillin molecules per enzyme trimer. Similar results were obtained from fluorimetric titrations, and for other inhibitors bearing features of the transition state. However, we observed apparent cooperativity between enzyme subunits and apparent lower stoichiometry when we used the recombinant enzyme not fully purified from hypoxanthine, which is moped from Escherichia coli cells. Results presented here prove that one-third-of-the-sites binding does not occur for trimeric PNP, and give the highly probable explanation why previous experiments were interpreted in terms of this phenomenon. (C) 2012 Elsevier Ltd. All rights reserved.