N-(9-((2R,3R,5S)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3-hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide | 84138-86-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-(9-((2R,3R,5S)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3-hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide
• 英文别名: N6-Benzoyl-5'-O-(dimethoxytrityl)-3'-deoxyadenosine；N-[9-[(2R,3R,5S)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-hydroxyoxolan-2-yl]purin-6-yl]benzamide
• CAS: 84138-86-3
• 化学式: C₃₈H₃₅N₅O₆
• 分子量: 657.726
• InChiKey: MLTMJWMWEVDUAV-FNLMIIKUSA-N

物化性质

• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  49
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  9

制备方法与用途

N-苯甲酰基-5′-O-[双(4-甲氧基苯基)苯基甲基]-3′-脱氧腺苷是一种嘌呤核苷类似物，具有广泛的抗肿瘤活性，特别针对惰性淋巴系统恶性肿瘤。其抗癌机制主要依赖于抑制DNA合成和诱导细胞凋亡等过程[1]。

反应信息

• 作为反应物：
  描述：

  N-(9-((2R,3R,5S)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3-hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide 在 4-二甲氨基吡啶 四氮唑 、 碘 、 三乙胺 、 N,N-二异丙基乙胺 、 苯磺酸 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 1.75h， 生成
  参考文献：
  名称：

  O-Alkyl-5',5'-dinucleoside phosphates as prodrugs of 3'-azidothymidine and cordycepin

  摘要：

  The syntheses of two O-alkyl-5',5'-dinucleoside phosphotriesters 2a and 2b as combined prodrugs of the antiviral drug AZT (1) and the antibiotic agent cordycepin (3) are described. 2a,b were obtained as a 1:1 diastereomeric mixture. The absolute configuration of the isolated diastereomers was determined by NOE NMR experiments and correlated with the migration characteristics on silica gel as well as the P-31-NMR chemical shift. The conformational features of 2b(R) and 2b(S) were determined m deuteriated dodecylphosphocholine micelles in aqueous solution using 2D-NOESY spectra and shown to be dependent on the configuration at phosphorus. Additionally, all new compounds were tested for their antiviral activities in HIV-1-infected CEM C113 and H9 cell systems. Although all compounds were able to significantly inhibit the HIV-1-induced cytopathogenic effect, only the phosphodiester 12 gave a selectivity index (SI(RT) = 2000) comparable to the reference compound AZT (1) (SI(RT) = 3000).

  DOI：

  10.1021/jo00052a053
• 作为产物：
  描述：

  N-{9-[(2R,3R,5S)-5-((R)-1,2-Dihydroxy-ethyl)-3-hydroxy-tetrahydro-furan-2-yl]-9H-purin-6-yl}-benzamide 在 吡啶 、 sodium tetrahydroborate 、 sodium periodate 作用下， 反应 14.5h， 生成 N-(9-((2R,3R,5S)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-3-hydroxytetrahydrofuran-2-yl)-9H-purin-6-yl)benzamide
  参考文献：
  名称：

  Arslan, Tuncer; Abraham, Anil T.; Hecht, Sidney M., Nucleosides and Nucleotides, 1998, vol. 17, # 1-3, p. 515 - 530

  摘要：

  DOI：

文献信息

• Improved procedure for the preparation of deoxynucleoside phosphoramidites: Arylphosphoramidites as new convenient intermediates for oligodeoxynucleotide synthesis
  作者：Jean-Louis Fourrey、Jeannette Varenne

  DOI：10.1016/s0040-4039(01)81480-5

  日期：1984.1

  A simplified procedure for the preparation of deoxynucleoside methyl- and arylphosphoramidites is described. Both types of phosphoramidites can be conveniently activated by N-methylaniline trifluoracetate for their use in oligodeoxynucleotide synthesis.

  描述了一种制备脱氧核苷甲基-和芳基磷酰胺的简化方法。两种类型的亚磷酰胺都可以方便地被N-甲基苯胺三氟乙酸酯活化，以用于寡聚脱氧核苷酸的合成。
• LOCKED NUCLEIC ACID CYCLIC DINUCLEOTIDE COMPOUNDS AND USES THEREOF
  申请人：ADURO BIOTECH, INC.

  公开号：US20190185511A1

  公开（公告）日：2019-06-20

  The present invention provides highly active locked nucleic acid cyclic-dinucleotide (LNA-CDN) immune stimulators that activate DCs via the cytoplasmic receptor known as STING (Stimulator of Interferon Genes). In particular, the LNA-CDNs of the present invention are provided in the form of a composition comprising one or more cyclic dinucleotides that induce human STING-dependent type I interferon production, wherein the cyclic dinucleotides present in the composition have at least one 2′, 4′ locked nucleic acids within the cyclic dinucleotide.

  本发明提供了高活性的锁定核酸环二核苷酸（LNA-CDN）免疫刺激剂，通过细胞质受体STING（干扰素基因刺激剂）激活DCs。具体而言，本发明的LNA-CDNs以一种组合物的形式提供，该组合物包括一种或多种诱导人类STING依赖型I型干扰素产生的环二核苷酸，其中组合物中的环二核苷酸至少有一个2′, 4′锁定核酸。
• [EN] CYCLIC DI-NUCLEOTIDE COMPOUNDS AS STING AGONISTS<br/>[FR] COMPOSÉS DI-NUCLÉOTIDIQUES CYCLIQUES EN TANT QU'AGONISTES DE STING
  申请人：MERCK SHARP & DOHME

  公开号：WO2017027645A1

  公开（公告）日：2017-02-16

  A class of polycyclic compounds of general formula (II), of general formula (II'), or of general formula (II"), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3a, R4, R4a, R5, R6, R6a, R7, R7a, R8, and R8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

  提供一类多环化合物，其一般化学式为(II)，一般化学式为(II')或一般化学式为(II")，其中在此处定义了Base1、Base2、Y、Ya、Xa、Xa1、Xb、Xb1、Xc、Xc1、Xd、Xd1、R1、R1a、R2、R2a、R3a、R4、R4a、R5、R6、R6a、R7、R7a、R8和R8a，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。还提供了合成和使用这些化合物的方法。
• Phosphonate inhibitors of HCV
  申请人：Boojamra G. Constantine

  公开号：US20080107628A1

  公开（公告）日：2008-05-08

  A compound of Formula I, Formula II, Formula III, or Formula IV: or a pharmaceutically acceptable salt, solvate, and/or ester thereof, therapeutic compositions containing such compounds, and therapeutic methods that include the administration of such compounds.

  一种具有I式、II式、III式或IV式的化合物，或其药学上可接受的盐、溶剂和/或酯，包含这种化合物的治疗组合物，以及包括给予这种化合物的治疗方法。
• Novel Poxin Stable cGAMP‐Derivatives Are Remarkable STING Agonists
  作者：Samuele Stazzoni、Daniel F. R. Böhmer、Fabian Hernichel、Dilara Özdemir、Aikaterini Pappa、David Drexler、Stefan Bauernfried、Gregor Witte、Mirko Wagner、Simon Veth、Karl‐Peter Hopfner、Veit Hornung、Lars M. König、Thomas Carell

  DOI：10.1002/anie.202207175

  日期：2022.10.4

  Dideoxy-cyclic-dinucleotide analogs of cGAS/STING second messenger 2′,3′-cGAMP are prepared using a new and concise synthetic combination of phosphoramidite and phosphotriester chemistry. The dideoxy analogs are found to exhibit remarkable in cellulo and in vitro properties, are stable against degradation by poxvirus immune nucleases, and exhibit superior tumor growth control in a mouse model.

  cGAS/STING 第二信使 2′，3′-cGAMP 的二脱氧环二核苷酸类似物是使用亚磷酰胺和磷酸三酯化学的新颖简洁的合成组合制备的。发现双脱氧类似物在纤维素和体外特性中表现出显着的特性，对痘病毒免疫核酸酶的降解保持稳定，并且在小鼠模型中表现出卓越的肿瘤生长控制。