2-(5-phenyl)pentyn-1-yl-5'-N-ethylcarboxamidoadenosine | 155036-84-3

• 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: 2-(5-phenyl)pentyn-1-yl-5'-N-ethylcarboxamidoadenosine
• 英文别名: (2S,3S,4R,5R)-5-[6-amino-2-(5-phenylpent-1-ynyl)purin-9-yl]-N-ethyl-3,4-dihydroxyoxolane-2-carboxamide
• CAS: 155036-84-3
• 化学式: C₂₃H₂₆N₆O₄
• 分子量: 450.497
• InChiKey: HJEMREITHZKJMZ-QPXQOZNCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  148
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(5-phenyl)pentyn-1-yl-5'-N-ethylcarboxamidoadenosine 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以62%的产率得到(2S,3S,4R,5R)-5-[6-Amino-2-(5-phenyl-pentyl)-purin-9-yl]-3,4-dihydroxy-tetrahydro-furan-2-carboxylic acid ethylamide
  参考文献：
  名称：

  2-Alkenyl and 2-Alkyl Derivatives of Adenosine and Adenosine-5‘-N-Ethyluronamide:  Different Affinity and Selectivity of E- and Z-Diastereomers at A_2A Adenosine Receptors

  摘要：

  A series of new 2-(ar)alkenyl, both Z- and E-diastereomers, and 2-alkyl derivatives of adenosine-5'-N-ethyluronamide (NECA) and adenosine were synthesized and evaluated for their interaction with the A(1) and A(2A) adenosine receptors, to better understand the conformational requirements of the receptor area interacting with the substituents in the 2- and 5'-positions. Partial reduction of the triple bond in 2-alkynyl derivatives of NECA led to compounds whose activity at the A(2A) receptor subtype was related to Z-E-isomerism, the E-diastereomers being more potent and selective than the Z-ones. Saturation of the side chain markedly reduced compound affinity at adenosine receptors. Specifically, compounds bearing an (E)-alkenyl chain, while maintaining the same affinity at A(2A) receptors as the corresponding alkynyl derivatives, showed an increase in A(2A) vs A(1) selectivity. Hence, the new nucleosides (E)-2-hexenylNECA (12a) and (E)-2-(phenylpenteny1)NECA (12b) exhibited both high A(2A) receptor affinity (K-i = 1.6 and 3.5 nM, respectively) and A(2A) VS A(1) selectivity (157- and 290-fold, respectively). Moreover, 12a displayed potent antiaggregatory activity, similar to that of the reference compound NECA. Comparison between NECA and adenosine derivatives further demonstrated that the 5'-ethylcarboxamido group is critical for the A(2A) affinity. These studies indicated that the orientation of the substituent in the 2-position and the nature of the 5'-group in adenosine derivatives are critical to achieve high affinity and selectivity at the A(2A) adenosine receptor subtype.

  DOI：

  10.1021/jm960376g
• 作为产物：
  描述：

  5-苯基-1-戊炔 在 (Ph₃P₀₂PdCl₂ copper(l) iodide 、 三乙胺 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 生成 2-(5-phenyl)pentyn-1-yl-5'-N-ethylcarboxamidoadenosine
  参考文献：
  名称：

  Potent and Selective Ligands for Adenosine Binding Sites

  摘要：

  A number of selective ligands for the different binding sites of adenosine have been synthesized and tested in several pharmacological models. The aim of these synthetic efforts is both to improve the knowledge of structure-activity relationships in the adenosine-related biological systems and to develop drugs from some of these molecules.

  DOI：

  10.1080/07328319708006189

文献信息

• 2-Aralkynyl and 2-Heteroalkynyl Derivatives of Adenosine-5'-N-Ethyluronamide as Selective A2a Adenosine Receptor Agonists
  作者：Gloria Cristalli、Emidio Camaioni、Sauro Vittori、Rosaria Volpini、Pier Andrea Borea、Annamaria Conti、Silvio Dionisotti、Ennio Ongini、Angela Monopoli

  DOI：10.1021/jm00009a007

  日期：1995.4

  2-heteroaralkynyl derivatives of NECA were synthesized and studied in binding and functional assays to assess their potency for the A2a compared to A1 adenosine receptors. Compounds bearing an aromatic or heteroaromatic ring, conjugated to the triple bond, showed generally weaker activity at the A2a receptor and lower selectivity (A2a vs A1) than the alkylakynyl derivatives previously reported. However,

  合成了一系列NECA的新的2-芳炔基和2-杂芳炔基衍生物，并在结合和功能测定中进行了研究，以评估它们与A1腺苷受体相比对A2a的效力。与先前报道的烷基炔基衍生物相比，带有与三键结合的芳香或杂芳香环的化合物通常对A2a受体的活性更弱，选择性更低（A2a对A1）。但是，（4-甲酰基苯基）-乙炔基衍生物17在低纳摩尔范围内具有亲和力，并且对A2a受体具有高选择性（约160倍）。杂原子的存在改善了血管舒张活性，2-噻唑基乙炔基衍生物30是该系列中最有效的。在三键和苯环之间引入亚甲基有利于A2a结合亲和力，并且发现5-苯基-1-戊炔基衍生物24在A2a受体上是高度有效的和选择性的（约180倍）。关于抗血小板活性，与NECA和N-乙基-1'-脱氧-1'-（6-氨基-2-己炔基9H-嘌呤-9-相比，芳族或杂芳族环的存在降低了效能。 yl）-β-D-核呋喃核糖酰胺（HENECA）。亚甲基的引入仅在该基团与
• Potent and Selective Ligands for Adenosine Binding Sites
  作者：G. Cristalli、E. Camaioni、E. Di Francesco、A. Eleuteri、S. Vittori、R. Volpini

  DOI：10.1080/07328319708006189

  日期：1997.7

  A number of selective ligands for the different binding sites of adenosine have been synthesized and tested in several pharmacological models. The aim of these synthetic efforts is both to improve the knowledge of structure-activity relationships in the adenosine-related biological systems and to develop drugs from some of these molecules.
• 2-Alkenyl and 2-Alkyl Derivatives of Adenosine and Adenosine-5‘-<i>N</i>-Ethyluronamide:  Different Affinity and Selectivity of <i>E</i>- and <i>Z</i>-Diastereomers at A_2A Adenosine Receptors
  作者：Sauro Vittori、Emidio Camaioni、Emanuela Di Francesco、Rosaria Volpini、Angela Monopoli、Silvio Dionisotti、Ennio Ongini、Gloria Cristalli

  DOI：10.1021/jm960376g

  日期：1996.1.1

  A series of new 2-(ar)alkenyl, both Z- and E-diastereomers, and 2-alkyl derivatives of adenosine-5'-N-ethyluronamide (NECA) and adenosine were synthesized and evaluated for their interaction with the A(1) and A(2A) adenosine receptors, to better understand the conformational requirements of the receptor area interacting with the substituents in the 2- and 5'-positions. Partial reduction of the triple bond in 2-alkynyl derivatives of NECA led to compounds whose activity at the A(2A) receptor subtype was related to Z-E-isomerism, the E-diastereomers being more potent and selective than the Z-ones. Saturation of the side chain markedly reduced compound affinity at adenosine receptors. Specifically, compounds bearing an (E)-alkenyl chain, while maintaining the same affinity at A(2A) receptors as the corresponding alkynyl derivatives, showed an increase in A(2A) vs A(1) selectivity. Hence, the new nucleosides (E)-2-hexenylNECA (12a) and (E)-2-(phenylpenteny1)NECA (12b) exhibited both high A(2A) receptor affinity (K-i = 1.6 and 3.5 nM, respectively) and A(2A) VS A(1) selectivity (157- and 290-fold, respectively). Moreover, 12a displayed potent antiaggregatory activity, similar to that of the reference compound NECA. Comparison between NECA and adenosine derivatives further demonstrated that the 5'-ethylcarboxamido group is critical for the A(2A) affinity. These studies indicated that the orientation of the substituent in the 2-position and the nature of the 5'-group in adenosine derivatives are critical to achieve high affinity and selectivity at the A(2A) adenosine receptor subtype.