8-benzyloxyguanosine | 3868-36-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 8-benzyloxyguanosine
• 英文别名: 8-(Benzyloxy)guanosine；2-amino-9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-8-phenylmethoxy-1H-purin-6-one
• CAS: 3868-36-8
• 化学式: C₁₇H₁₉N₅O₆
• 分子量: 389.368
• InChiKey: RNSGUQLXDMZREX-SDBHATRESA-N

物化性质

• 熔点：
  >190°C (dec.)
• 密度：
  1.80±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜（微溶）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  164
• 氢给体数：
  5
• 氢受体数：
  8

制备方法与用途

8-苯基甲氧基)鸟苷是一种鸟苷类似物，而某些鸟苷类似物具有免疫刺激活性，在一些动物模型中还能诱导I型干扰素产生，从而发挥抗病毒作用。研究表明，这些类似物的功能活性依赖于Toll样受体7（TLR7）的激活。

反应信息

• 作为反应物：
  描述：

  8-benzyloxyguanosine 在 palladium on carbon 、 氢气 、 溶剂黄146 、 sodium nitrite 作用下， 以 水 为溶剂， 生成 7,9-二氢-9-beta-D-呋喃核糖基-1H-嘌呤-2,6,8(3H)-三酮
  参考文献：
  名称：

  Oxidation of 9-β-d-ribofuranosyl uric acid by one-electron oxidants versus singlet oxygen and its implications for the oxidation of 8-oxo-7,8-dihydroguanosine

  摘要：

  Uric acid, a cellular antioxidant, undergoes oxidation in the presence of one-electron oxidants as well as singlet oxygen. In the present work, the oxidation pathways and products formed from oxidation of the uric acid nucleoside are compared to the more commonly studied uric acid free base. A wider distribution of products, including allantoin, urea, caffolide, and 5-carboxamido-5-hydroxyhydantoin nucleosides, are formed when the N9 position of uric acid is glycosylated. The oxidation pathways share some features in common with the oxidation of 8-oxo-7,8-dihydroguanosine, but the additional spectrum of products implies that the combination of oxidative and deaminative damage to guanosine may lead to a more complex set of DNA lesions than originally described. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2010.11.123
• 作为产物：
  描述：

  鸟苷 在 溴 作用下， 以 二甲基亚砜 为溶剂， 反应 42.0h， 生成 8-benzyloxyguanosine
  参考文献：
  名称：

  Reactivity toward Singlet Oxygen of a 7,8-Dihydro-8-oxoguanosine ("8-Hydroxyguanosine") Formed by Photooxidation of a Guanosine Derivative

  摘要：

  Total quenching (k(r) + k(q)) and chemical reaction rates (k(r)) for the removal of singlet oxygen by 2,3',5'-tris((tert-butyldimethylsilyl)oxy)guanos (1) and its oxidation product, 2',3',5'-tris((tert-butyldimethylsilyl)oxy)-7,8-dihydro-8-oxoguanosine (2), were determined by the time-resolved infrared luminescence technique and competition experiments, respectively. Compound 2 is two orders of magnitude more reactive with singlet oxygen than 1. A mechanism for the formation of 2 from 1 with singlet oxygen is proposed.

  DOI：

  10.1021/ja00129a004

文献信息

• Spiroiminodihydantoin as an Oxo-Atom Transfer Product of 8-Oxo-2‘-deoxyguanosine Oxidation by Chromium(V)
  作者：Peter G. Slade、Nigel D. Priestley、Kent D. Sugden

  DOI：10.1021/ol701667t

  日期：2007.10.1

  Oxidation of the DNA lesion 8-oxo-2'-deoxyguanosine by the two electron oxidants N,N'-ethylenebis(salicylideneanimato)oxochromium(V) (Cr(V)-salen) and bis(2-ethyl-2-hydroxybutyrato)oxochromium(V) (Cr(V)-ehba) at neutral pH forms spiroiminodihydantoin by an oxo-atom transfer mechanism. The chromium complexes are models of a DNA oxidation pathway caused by the carcinogen chromate.

  DNA损伤8-oxo-2'-deoxyguanosine被两种电子氧化剂N，N'-亚乙基双（水杨基亚氨基）氧铬（V）（Cr（V）-salen）和双（2-乙基-2-羟基丁酰）氧化在中性pH值上的oxochromium（V）（Cr（V）-ehba）通过氧原子转移机制形成spiroiminodihydantoin。铬配合物是由致癌物铬酸盐引起的DNA氧化途径的模型。
• Structure-based design of guanosine analogue inhibitors targeting GTP cyclohydrolase IB towards a new class of antibiotics
  作者：George N. Samaan、Naduni Paranagama、Ayesha Haque、David A. Hecht、Manal A. Swairjo、Byron W. Purse

  DOI：10.1016/j.bmcl.2019.126818

  日期：2020.1

  distinct from the human homologue GCYH-IA. A comparison of the crystal structures of GCYH-IA and -IB with the nM inhibitor 8-oxo-GTP bound shows that the active site of GCYH-IB is larger and differently shaped. Based on this structural information, we designed and synthesized a small set of 8-oxo-G derivatives with ether linkages at O6 and O8 expected to displace water molecules from the expanded active

  GTP环水解酶（GCYH-I）是叶酸生物合成途径中的一种酶，以前尚未被用作抗生素靶标，尽管包括淋病奈瑟菌在内的几种病原体都使用某种形式的GCYH-IB酶，其结构与人的同源基因不同GCYH-IA。GCYH-IA和-IB与nM抑制剂8-oxo-GTP结合的晶体结构的比较表明，GCYH-IB的活性位点更大且形状不同。基于此结构信息，我们设计和合成了少量的在O6和O8带有醚键的8-氧代-G衍生物，这些衍生物有望将水分子从GCYH-IB的扩展活性位点转移出来。这些化合物中最有效的G3对GCYH-IB具有选择性，
• Use of 8-substituted guanine derivatives in the manufacture of a medicament.
  申请人：SCRIPPS CLINIC AND RESEARCH FOUNDATION

  公开号：EP0112632A2

  公开（公告）日：1984-07-04

  Compositions and methods for their use in modulating animal cellular responses are disclosed. The compositions include as an active agent an effective amount of an 8-substituted guanine derivative bonded 9-1' to an aldose having 5 or 6 carbon atoms in the aldose chain. The composition includes a diluent amount of a physiologically tolerable carrier. The guanine derivative is free of electrically charged functionality, while the 8-substituent has an electron withdrawing inductive effect greater than that of hydrogen and contains fewer than about 15 atoms. Animal cellular responses are modulated by contacting the cells with a composition of this invention.

  本发明公开了用于调节动物细胞反应的组合物和方法。 组合物包括有效量的8-取代鸟嘌呤衍生物作为活性剂，该衍生物以9-1'键与在醛糖链中具有5或6个碳原子的醛糖键合。 组合物包括生理上可耐受的载体稀释剂。 鸟嘌呤衍生物不带电荷官能团，而8-取代基的电子撤回感应效应大于氢的电子撤回感应效应，并且含有少于约15个原子。 通过用本发明的组合物接触细胞，可调节动物细胞反应。
• Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response
  申请人：Idera Pharmaceuticals, Inc.

  公开号：EP2341059A1

  公开（公告）日：2011-07-06

  The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.

  本发明提供了作为 TLRs 拮抗剂的新型免疫调节寡核苷酸（IRO）及其使用方法。这些IRO具有独特的序列，可抑制或抑制TLR介导的对TLR配体或TLR激动剂的信号传导。这些方法可用于预防和治疗癌症、自身免疫性疾病、气道炎症、炎症性疾病、传染性疾病、皮肤病、过敏、哮喘或由病原体引起的疾病。
• Stabilized immune modulatory RNA (SIMRA) compounds
  申请人：Idera Pharmaceuticals, Inc.

  公开号：EP2348112A2

  公开（公告）日：2011-07-27

  The invention relates to the therapeutic use of novel stabilized oligoribonucleotides as immune modulatory agents for immune therapy applications. Specifically, the invention provides novel RNA-based oligoribonucleotides with improved nuclease and RNase stability and that have immune modulatory activity through TLR7 and/or TLRB.

  本发明涉及新型稳定化寡核苷酸作为免疫调节剂在免疫治疗中的应用。具体而言，本发明提供了新型 RNA 基寡核苷酸，其核酸酶和 RNase 稳定性得到改善，并通过 TLR7 和/或 TLRB 具有免疫调节活性。