3'-DMTBS-5'-O-(4,4'-二甲氧基三苯甲基)-N2-异丁酰基酰基胞苷 | 81256-89-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: 3'-DMTBS-5'-O-(4,4'-二甲氧基三苯甲基)-N2-异丁酰基酰基胞苷
• 中文别名: 5'-O-[双(4-甲氧基苯基)苯甲基]-3'-O-[(叔丁基)二甲基硅基]-N2-异丁酰基鸟苷；5'-O-[双(4-甲氧基苯基)苯甲基]-3'-O-[(叔丁基)二甲基硅基]-N-(2-甲基-1-氧代丙基)鸟苷；3'-DMTBS-5'-O-(4,4'-二甲氧基三苯甲基)-N2-异丁酰基酰基鸟苷
• 英文名称: N-(9-((2R,3R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-((tert-butyldimethylsilyl)oxy)-3-hydroxytetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)isobutyramide
• 英文别名: 5'-DMT-3'-TBDMS-ibu-rG；N-[9-[(2R,3R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[tert-butyl(dimethyl)silyl]oxy-3-hydroxyoxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• CAS: 81256-89-5
• 化学式: C₄₁H₅₁N₅O₈Si
• 分子量: 769.97
• InChiKey: XAIQBZNFPUNWMQ-CJEGOSRCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.39
• 重原子数：
  55
• 可旋转键数：
  14
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  155
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3'-DMTBS-5'-O-(4,4'-二甲氧基三苯甲基)-N2-异丁酰基酰基胞苷 在 吡啶 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-(9-((2R,4R,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-((tert-butyldimethylsilyl)oxy)-3-oxotetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)isobutyramide
  参考文献：
  名称：

  [EN] CYCLIC DI-NUCLEOTIDE COMPOUNDS AS STING AGONISTS
  [FR] COMPOSÉS DI-NUCLÉOTIDIQUES CYCLIQUES UTILISÉS EN TANT QU'AGONISTES DE STING

  摘要：

  提供一类多环化合物，其一般式为(I)，其中定义了Base1、Base2、Y、Ya、Xa、Xa1、Xb、Xb1、Xc、Xc1、Xd、Xd1、R1、R1a、R2、R2a、R3a、R4、R5、R5a、R6、R6a、R7、R7a、R8、R8a和R9，这些化合物可能作为I型干扰素的诱导剂，特别是作为STING活性剂。还提供了化合物(I)的合成和使用过程。

  公开号：

  WO2020117624A1
• 作为产物：
  描述：

  鸟苷 在 吡啶 、 咪唑 、 三甲基氯硅烷 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 10.58h， 生成 3'-DMTBS-5'-O-(4,4'-二甲氧基三苯甲基)-N2-异丁酰基酰基胞苷
  参考文献：
  名称：

  COMPOUNDS FOR TREATING BACTERIAL INFECTIONS

  摘要：

  本发明涉及一类新型鸟嘌呤核苷酸类似物，其抑制RelA和Relseq的合成活性，并具有抗细菌活性。本发明还涉及包括这些化合物的药物组合物，以及利用这些化合物或组合物来对抗细菌和治疗细菌感染的方法。

  公开号：

  US20110086813A1

文献信息

• Modified phosphotriester method for chemical synthesis of ribooligonucleotides. Part I. Synthesis of riboundecaadenylate and two fragments constituting the sequence of R-17 translation control signal
  作者：Wing L. Sung、Saran A. Narang

  DOI：10.1139/v82-021

  日期：1982.1.15

  A modified phosphotriester method has been successfully applied for the chemical synthesis of ribooligonucleotides. The starting material is a fully protected ribomononucleoside containing a 3′-phosphotriester group 5. The coupling reaction is performed using mesitylenesulfonyl tetrazole and purification of the product achieved using reversed phase column chromatography. The effectiveness of this method has been demonstrated by achieving an efficient and rapid synthesis of r-A₇, r-A₁₁, r5′-AAACAUGAGGA-3′, and r5′-UUACCCAUGU-3′ (R-17, translation control sequence).

  一种改良的磷酸三酯方法已成功应用于核糖寡核苷酸的化学合成。起始物是含有3'-磷酸三酯基团的完全保护的核糖单核苷酸。偶联反应使用二甲苯磺酰四唑进行，并通过反相柱层析纯化产物。该方法的有效性已通过成功合成r-A₇、r-A₁₁、r5′-AAACAUGAGGA-3′和r5′-UUACCCAUGU-3′（R-17，翻译控制序列）来证明。
• Enzymatic Preparation of 2′–5′,3′–5′-Cyclic Dinucleotides, Their Binding Properties to Stimulator of Interferon Genes Adaptor Protein, and Structure/Activity Correlations
  作者：Barbora Novotná、Lenka Vaneková、Martin Zavřel、Miloš Buděšínský、Milan Dejmek、Miroslav Smola、Ondrej Gutten、Zahra Aliakbar Tehrani、Markéta Pimková Polidarová、Andrea Brázdová、Radek Liboska、Ivan Štěpánek、Zdeněk Vavřina、Tomáš Jandušík、Radim Nencka、Lubomír Rulíšek、Evžen Bouřa、Jiří Brynda、Ondřej Páv、Gabriel Birkuš

  DOI：10.1021/acs.jmedchem.9b01062

  日期：2019.12.12

  (NFκB) signaling cascades. In this work, we describe an enzymatic preparation of 2′–5′,3′–5′-cyclic dinucleotides (2′3′CDNs) with use of cyclic GMP–AMP synthases (cGAS) from human, mouse, and chicken. We profile substrate specificity of these enzymes by employing a small library of nucleotide-5′-triphosphate (NTP) analogues and use them to prepare 33 2′3′CDNs. We also determine affinity of these CDNs to

  环状二核苷酸是环状GMP-AMP合酶（cGAS）-干扰素基因刺激（STING）途径的第二信使，在识别肿瘤细胞和病毒或细菌感染中起着重要作用。它们与STING衔接蛋白结合并通过TANK结合激酶1（TBK1）/干扰素调节因子3（IRF3）和核因子-κB（IκB）激酶（IKK）/核因子-κB（NFκB）抑制剂触发细胞因子的表达信号级联。在这项工作中，我们描述了使用人，小鼠和鸡的环状GMP-AMP合成酶（cGAS）酶法制备2'-5'，3'-5'-环二核苷酸（2'3'CDNs）的方法。我们通过使用一个小的核苷酸5'-三磷酸（NTP）类似物文库来分析这些酶的底物特异性，并使用它们来制备33个2'3'CDN。我们还确定了这些CDN对基于细胞和生化分析的五种不同STING单倍型的亲和力，并描述了它们对所有STING单倍型的最佳活性所需的特性。接下来，我们研究它们对人外周血单核细胞（PBMC）诱导的细胞因子
• [EN] CYCLIC DINUCLEOTIDES AS STING AGONISTS<br/>[FR] DINUCLÉOTIDES CYCLIQUES EN TANT QU'AGONISTES DE STING
  申请人：JANSSEN BIOTECH INC

  公开号：WO2018098203A1

  公开（公告）日：2018-05-31

  Disclosed are compounds, compositions and methods for treating viral infections, diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I) as follows: [Formula (I) should be inserted here] wherein R1A, R1B, R1c, B1, R2A, and R2B are defined herein.

  揭示了用于治疗受STING调节影响的病毒感染、疾病、综合症或紊乱的化合物、组合物和方法。这些化合物由以下式（I）表示：[应在此处插入式（I）]其中R1A、R1B、R1c、B1、R2A和R2B在此处被定义。
• [EN] CYCLIC DINUCLEOTIDES AS STING AGONISTS<br/>[FR] DINUCLÉOTIDES CYCLIQUES UTILISÉS EN TANT QU'AGONISTES DE STING
  申请人：JANSSEN BIOTECH INC

  公开号：WO2018138685A3

  公开（公告）日：2018-10-04
• ppGpp analogues inhibit synthetase activity of Rel proteins from Gram-negative and Gram-positive bacteria
  作者：Ezequiel Wexselblatt、Jehoshua Katzhendler、Raspudin Saleem-Batcha、Guido Hansen、Rolf Hilgenfeld、Gad Glaser、Roee R. Vidavski

  DOI：10.1016/j.bmc.2010.04.064

  日期：2010.6.15

  A prominent feature of the stringent response is the accumulation of two unusual phosphorylated derivatives of GTP and GDP (pppGpp: 5'-triphosphate-3'-diphosphate, and ppGpp: 5'-3'-bis-diphosphate), collectively called (p) ppGpp, within a few seconds after the onset of amino-acid starvation. The synthesis of these 'alarmone' compounds is catalyzed by RelA homologues. Other features of the stringent response include inhibition of stable RNA synthesis and modulation of transcription, replication, and translation. (p) ppGpp accumulation is important for virulence induction, differentiation and antibiotic resistance. We have synthesized a group of (p) ppGpp analogues and tested them as competitive inhibitors of Rel proteins in vitro. 2'-Deoxyguanosine-3'-5'-di(methylene bisphosphonate) [compound (10)] was found as an inhibitor that reduces ppGpp formation in both Gram-negative and Gram-positive bacteria. In silico docking together with competitive inhibition analysis suggests that compound (10) inhibits activity of Rel proteins by competing with GTP/GDP for its binding site.As Rel proteins are completely absent in mammalians, this appears to be a very attractive approach for the development of novel antibacterial agents. (C) 2010 Elsevier Ltd. All rights reserved.