4-amino-5-iodo-7-[2,3,5-tris-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine | 1252858-34-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡咯并嘧啶核苷和核苷酸
• 英文名称: 4-amino-5-iodo-7-[2,3,5-tris-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine
• 英文别名: 2',3',5'-tri-O-TBS-7-iodotubercidin；4-amino-5-iodo-7-[2,3,5-tris-O-(tert-butyldimethylsilyl)-β-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine；4-Amino-5-iodo-7-[2,3,5-tris-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine；7-[(2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[[tert-butyl(dimethyl)silyl]oxymethyl]oxolan-2-yl]-5-iodopyrrolo[2,3-d]pyrimidin-4-amine
• CAS: 1252858-34-6
• 化学式: C₂₉H₅₅IN₄O₄Si₃
• 分子量: 734.941
• InChiKey: BMNJUAMOVKICNS-HUBRGWSESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.32
• 重原子数：
  41
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  93.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-amino-5-iodo-7-[2,3,5-tris-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 4-amino-7-(β-D-ribofuranosyl)-5-(thiazol-2-yl)-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Synthesis and Significant Cytostatic Activity of 7-Hetaryl-7-deazaadenosines

  摘要：

  A series of 7-aryl- and 7-hetaryl-7-deazaadenosines were prepared by the cross-coupling reactions of unprotected or protected 7-iodo-7-deazaadenosines with (het)arylboronic acids, stannanes, or zinc halides. Nucleosides bearing 5-membered heterocycles at the position 7 exerted potent in vitro antiproliferative effects against a broad panel of hematological and solid tumor cell lines. Cell cycle analysis indicated profound inhibition of RNA synthesis and induction of apoptosis in treated cells. Intracellular conversion to triphosphates has been detected with active compounds. The triphosphate metabolites showed only a weak inhibitory effect on human RNA polymerase II, suggesting potentially other mechanisms for the inhibition of RNA synthesis and quick onset of apoptosis. Initial in vivo evaluation demonstrated an effect of 7-(2-thienyl)-7-deazaadenine ribonucleoside on the survival rate in syngeneic P388D1 mouse leukemia model.

  DOI：

  10.1021/jm2005173
• 作为产物：
  描述：

  在 甲醇 作用下， 以40%的产率得到4-amino-5-iodo-7-[2,3,5-tris-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-7H-pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Synthesis and Significant Cytostatic Activity of 7-Hetaryl-7-deazaadenosines

  摘要：

  A series of 7-aryl- and 7-hetaryl-7-deazaadenosines were prepared by the cross-coupling reactions of unprotected or protected 7-iodo-7-deazaadenosines with (het)arylboronic acids, stannanes, or zinc halides. Nucleosides bearing 5-membered heterocycles at the position 7 exerted potent in vitro antiproliferative effects against a broad panel of hematological and solid tumor cell lines. Cell cycle analysis indicated profound inhibition of RNA synthesis and induction of apoptosis in treated cells. Intracellular conversion to triphosphates has been detected with active compounds. The triphosphate metabolites showed only a weak inhibitory effect on human RNA polymerase II, suggesting potentially other mechanisms for the inhibition of RNA synthesis and quick onset of apoptosis. Initial in vivo evaluation demonstrated an effect of 7-(2-thienyl)-7-deazaadenine ribonucleoside on the survival rate in syngeneic P388D1 mouse leukemia model.

  DOI：

  10.1021/jm2005173

文献信息

• The Structure-Based Design of SARS-CoV-2 nsp14 Methyltransferase Ligands Yields Nanomolar Inhibitors
  作者：Tomáš Otava、Michal Šála、Fengling Li、Jindřich Fanfrlík、Kanchan Devkota、Sumera Perveen、Irene Chau、Paknoosh Pakarian、Pavel Hobza、Masoud Vedadi、Evzen Boura、Radim Nencka

  DOI：10.1021/acsinfecdis.1c00131

  日期：2021.8.13

  In this study, we have focused on the structure-based design of the inhibitors of one of the two SARS-CoV-2 methyltransferases (MTases), nsp14. This MTase catalyzes the transfer of the methyl group from S-adenosyl-l-methionine (SAM) to cap the guanosine triphosphate moiety of the newly synthesized viral RNA, yielding the methylated capped RNA and S-adenosyl-l-homocysteine (SAH). As the crystal structure

  在这项研究中，我们重点关注两种 SARS-CoV-2 甲基转移酶 (MTase) 之一 nsp14 的抑制剂的基于结构的设计。该 MTase 催化甲基从S-腺苷-l-甲硫氨酸 (SAM) 转移，以对新合成的病毒 RNA 的三磷酸鸟苷部分进行加帽，产生甲基化加帽 RNA 和S-腺苷-l-高半胱氨酸 (SAH)。由于SARS-CoV-2 nsp14的晶体结构未知，我们利用其与SARS-CoV nsp14的高度同源性，建立了其同源模型，这使我们能够鉴定出腺嘌呤核碱基修饰的新型SAH衍生物作为抑制剂这个重要的病毒目标。我们在体外合成并测试了所设计的化合物，并表明这些衍生物对这种关键酶具有前所未有的抑制活性。对接研究很好地解释了由连接子连接的芳香部分对 SAH 7-脱氮类似物的 7 位的贡献。
• NOVEL 7-DEAZAPURINE NUCLEOSIDES FOR THERAPEUTIC USES
  申请人：Bourderioux Aurelie

  公开号：US20150218201A1

  公开（公告）日：2015-08-06

  The invention provides compounds of formula I, wherein R1, R2 and R3 have values defined in the specification and a pharmaceutically acceptable salt thereof; or an optical isomer thereof; or a mixture of optical isomers, as well as compositions comprising such compounds and therapeutic methods that utilize such compounds and/or compositions.

  本发明提供了式子I的化合物，其中R1、R2和R3的值在规范中定义，并且其药学上可接受的盐；或其光学异构体；或其光学异构体的混合物，以及包含这些化合物的组合物和利用这些化合物和/或组合物的治疗方法。
• 7-deazapurine nucleosides for therapeutic uses
  申请人：Bourderioux Aurelie

  公开号：US09321800B2

  公开（公告）日：2016-04-26

  The invention provides compounds of formula I, wherein R1, R2 and R3 have values defined in the specification and a pharmaceutically acceptable salt thereof; or an optical isomer thereof; or a mixture of optical isomers, as well as compositions comprising such compounds and therapeutic methods that utilize such compounds and/or compositions.

  本发明提供了公式I的化合物，其中R1，R2和R3的值在规范中定义，并且其药学上可接受的盐；或其光学异构体；或光学异构体的混合物，以及包括这些化合物的组合物和利用这些化合物和/或组合物的治疗方法。
• [EN] NOVEL 7-DEAZAPURINE NUCLEOSIDES FOR THERAPEUTIC USES<br/>[FR] NOUVEAUX NUCLÉOSIDES 7-DÉAZAPURINE À DES FINS THÉRAPEUTIQUES
  申请人：ACAD OF SCIENCE CZECH REPUBLIC

  公开号：WO2010121576A3

  公开（公告）日：2011-06-16