8-(1-hexynyl)-Adenosine

• 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-(1-hexynyl)-Adenosine
• 英文别名: 8-(1-hexyn-1-yl)adenosine；(2R,3R,4S,5R)-2-(6-amino-8-hex-1-ynylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• 化学式: C₁₆H₂₁N₅O₄
• 分子量: 347.374
• InChiKey: IJAPUBHYHCDJEW-RVXWVPLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-己炔 、 腺苷 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 8-(1-hexynyl)-Adenosine
  参考文献：
  名称：

  Introduction of alkynyl chains on C-8 of adenosine led to very selective antagonists of the A 3 adenosine receptor

  摘要：

  Some 8-alkynyladenosines were synthesized and evaluated for their adenosine receptor activity, utilizing radioligand binding studies (A(1), A(2A), A(3)) or adenylyl cyclase activity assays (A(2B)). Furthermore, the maximal induction of guanosine 5 '-(gamma -thio)triphosphate ([S-35]GTP gammaS) binding to G proteins and the inhibition of NECA-stimulated binding, in membranes of CHO cells which express the human A(3) receptor, were used to determine the intrinsic activity of these nucleosides at the A(3) adenosine receptor. The results showed that these new adenosine derivatives are very selective ligands for the A(3) receptor subtype and behave as adenosine antagonists, since they do not stimulate basal [S-35]GTP gammaS binding, but inhibit NECA-stimulated binding. This is the first report that adenosine derivatives, with unmodified ribose moiety, are adenosine receptor antagonists. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00347-x

文献信息

• Efficient Sonogashira Coupling of Unprotected Halonucleosides in Aqueous Solvents Using Water-Soluble Palladium Catalysts
  作者：Joon Hyung Cho、Caitlin D. Prickett、Kevin H. Shaughnessy

  DOI：10.1002/ejoc.201000313

  日期：2010.7

  prompted the continuing development of efficient synthetic methods for their preparation. We report an efficient andenvironmentally benign Sonogashira coupling reaction for alkynylation of unprotected halonucleosides in an aqueous solvent. The combination of Pd(OAc)2, CuI, and TXPTS [trisodium tri(2,4-dimethyl-5-sulfonatophenyl)phosphane] provided an effective catalyst for the alkynylation of 8-bromopurines

  C-炔基化核苷的各种应用促进了其制备的有效合成方法的持续发展。我们报告了一种有效且对环境无害的 Sonogashira 偶联反应，用于在水性溶剂中对未受保护的卤代核苷进行炔基化。Pd(OAc)2、CuI 和 TXPTS [三(2,4-二甲基-5-磺基苯基)膦三钠] 的组合为 H2O/CH3CN 中 8-溴嘌呤和 5-碘尿苷的炔基化提供了有效的催化剂 (1 :1) 产率范围为 42 至 98 %。
• Purine and deazapurine nucleosides: synthetic approaches, molecular modelling and biological activity
  作者：Gloria Cristalli、Stefano Costanzi、Catia Lambertucci、Sara Taffi、Sauro Vittori、Rosaria Volpini

  DOI：10.1016/s0014-827x(03)00019-3

  日期：2003.3

  A number of ligands for the adenosine binding sites has been obtained by using nucleoside convergent and divergent synthesis. Most of our nucleosides have been synthesized by coupling 2,6-dichloropurine (1), 2,6-dichloro-1-deazapurine (2), 2,6-dichloro-3-deazapurine (3) with ribose, 2- and 3-deoxyribose and 2,3-dideoxyribose derivatives. The use of these versatile synthons allowed the introduction of various substituents in 2- and/or 6-positions. The glycosylation site and the anomeric configuration of the obtained nucleosides were assigned on the basis of spectroscopic studies and confirmed by molecular models. A series of potent adenosine receptor ligands has been obtained by using divergent approaches, mostly starting from guanosine. Substitutions in 2, 6, 8, and 5' position of adenosine molecule led to ligands selective for the different adenosine receptor subtypes. Furthermore, we investigated the molecular bases of the different behavior of 2- and 8-alkynyl adenosines, by means of NMR experiments and molecular modeling studies. With docking experiments, we demonstrated that the two class of molecules should have different binding modes that explain their different degree of affinity and the shift of their activity from agonistic (2-substituted derivatives) to antagonistic (8-substituted derivatives).
• SYNTHESIS AND ADENOSINE RECEPTOR AFFINITY AND POTENCY OF 8-ALKYNYL DERIVATIVES OF ADENOSINE
  作者：C. Lambertucci、S. Costanzi、S. Vittori、R. Volpini、G. Cristalli

  DOI：10.1081/ncn-100002509

  日期：2001.3.31

  Adenosine derivatives bearing different (ar)alkynyl chains at the 8-position were synthesized and tested at human adenosine receptors. Binding studies showed that all compounds possess affinity for the A(3) subtype in the high nM range. Moreover, guanosine 5'-O-(3-[S-35]thio)triphosphate binding assay indicated that the 8-alkynyl adenosines behaved as antagonists of NECA at A(3) receptors.
• Introduction of alkynyl chains on C-8 of adenosine led to very selective antagonists of the A 3 adenosine receptor
  作者：Rosaria Volpini、Stefano Costanzi、Catia Lambertucci、Sauro Vittori、K.-N Klotz、Anna Lorenzen、Gloria Cristalli

  DOI：10.1016/s0960-894x(01)00347-x

  日期：2001.7

  Some 8-alkynyladenosines were synthesized and evaluated for their adenosine receptor activity, utilizing radioligand binding studies (A(1), A(2A), A(3)) or adenylyl cyclase activity assays (A(2B)). Furthermore, the maximal induction of guanosine 5 '-(gamma -thio)triphosphate ([S-35]GTP gammaS) binding to G proteins and the inhibition of NECA-stimulated binding, in membranes of CHO cells which express the human A(3) receptor, were used to determine the intrinsic activity of these nucleosides at the A(3) adenosine receptor. The results showed that these new adenosine derivatives are very selective ligands for the A(3) receptor subtype and behave as adenosine antagonists, since they do not stimulate basal [S-35]GTP gammaS binding, but inhibit NECA-stimulated binding. This is the first report that adenosine derivatives, with unmodified ribose moiety, are adenosine receptor antagonists. (C) 2001 Elsevier Science Ltd. All rights reserved.