2-碘-5’-乙基甲酰氨基-2’,3’-O-异丙基亚基腺苷 | 162936-24-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 2-碘-5’-乙基甲酰氨基-2’,3’-O-异丙基亚基腺苷
• 英文名称: N-ethyl-1'-deoxy-1'-(6-amino-2-iodo-9H-purin-9-yl)-2',3'-O-isopropylidene-β-D-ribofuranuronamide
• 英文别名: (3Ar,4R,6S,6aS)-4-(6-amino-2-iodopurin-9-yl)-N-ethyl-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxamide
• CAS: 162936-24-5
• 化学式: C₁₅H₁₉IN₆O₄
• 分子量: 474.258
• InChiKey: SRBUDLXECXRPCA-LOKDSWTASA-N

物化性质

• 熔点：
  204-206°C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-碘-5’-乙基甲酰氨基-2’,3’-O-异丙基亚基腺苷 在 甲酸 、 二碘甲烷 、 三乙胺 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.5h， 生成 2-iodo-N⁶-methoxy-5'-N-ethylcarboxamidoadenosine
  参考文献：
  名称：

  N⁶-Methoxy-2-alkynyladenosine Derivatives as Highly Potent and Selective Ligands at the Human A₃ Adenosine Receptor

  摘要：

  A new series of N-6-methoxy-2-(ar)alkynyladenosine derivatives has been synthesized and tested at the human recombinant adenosine receptors. Binding studies demonstrated that the new compounds possess high affinity and selectivity for the A(3) subtype. Among them, compounds bearing an N-methylcarboxamido substituent in the 4'-position showed the highest A(3) affinity and selectivity. In particular, the N-6-methoxy-2-p-acetylphenylethynylMECA (40; K-i A(3) = 2.5 nM, A(3) selectivity versus A(1) = 21 500 and A(2A) = 4200) results in one of the most potent and selective agonists at the human A(3) adenosine receptor reported so far. Furthermore, functional assay, performed with selected new compounds, revealed that the presence of an alkylcarboxamido group in the 4'-position seems to be essential to obtain full agonists at the A(3) subtype. Finally, results of molecular docking analysis were in agreement with binding and functional data and could explain the high affinity and potency of the new compounds.

  DOI：

  10.1021/jm060963u
• 作为产物：
  描述：

  (3aR,4R,6S,6aS)-4-[6-(benzotriazol-1-yloxy)-2-iodopurin-9-yl]-N-ethyl-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxamide 在 氨 作用下， 以 水 、 乙腈 为溶剂， 反应 3.0h， 以96%的产率得到2-碘-5’-乙基甲酰氨基-2’,3’-O-异丙基亚基腺苷
  参考文献：
  名称：

  Linear and convergent approaches to 2-substituted adenosine-5′-N-alkylcarboxamides

  摘要：

  Herein we report both linear and convergent pathways for the preparation of 2-alkynyl substituted adenosine-5'-N-ethylcarboxamides via the versatile synthetic intermediate, 2-iodoadenosine-5'-N-ethylcarboxamide (13). The linear approach afforded 13 in an overall yield of 30% from guanosine over eight synthetic steps. The convergent approach was shorter, but proceeded in lower yield (five steps, 20% yield). Both approaches compare favourably with previously reported syntheses of 13, which has been prepared in 15% yield from guanosine over nine steps. 2-Iodoadenosine-5'-N-ethylcarboxamide (13) was subsequently converted to HENECA (2) and PHPNECA (3) to exemplify the utility of this approach for the preparation of potent A(2A) adenosine receptor agonists. The linear approach was also amenable to the synthesis of 2-fluoropurine ribosides, which were subsequently elaborated into 2-alkylaminoadenosine-5'-N-ethylcarboxamides. Furthermore, both of these synthetic approaches are readily amenable to the synthesis of adenosine analogues with varied 2-, 6- and 5'-substitution patterns. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.08.057

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
• Synthesis and Biological Activity of a New Series of <i>N</i>⁶-Arylcarbamoyl, 2-(Ar)alkynyl-<i>N</i>⁶-arylcarbamoyl, and <i>N</i>⁶-Carboxamido Derivatives of Adenosine-5‘-<i>N</i>-ethyluronamide as A₁ and A₃ Adenosine Receptor Agonists
  作者：Pier Giovanni Baraldi、Barbara Cacciari、Maria José Pineda de Las Infantas、Romeo Romagnoli、Giampiero Spalluto、Rosaria Volpini、Stefano Costanzi、Sauro Vittori、Gloria Cristalli、Neli Melman、Kyung-Sun Park、Xiao-duo Ji、Kenneth A. Jacobson

  DOI：10.1021/jm980147p

  日期：1998.8.1

  tested for affinity at A1 and A2A adenosine receptors in rat brain membranes and at cloned rat A3 receptors expressed in CHO cells. The derivatives contained the 5' substituent found in the potent, nonselective agonist 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-D-ribofuranuronamide++ + (NECA). While the carboxamido derivatives (9-13) showed affinity for A1 receptors, the urea derivatives (30-45) showed

  一系列新的 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-D-ribofurauronamide++ +-在嘌呤 6 位带有 N-芳基脲或 N-芳基甲酰胺基团已经合成了在 2 位与卤素或炔基链结合的 N-芳基脲和 N-芳基脲，并测试了对大鼠脑膜中 A1 和 A2A 腺苷受体以及在 CHO 细胞中表达的克隆大鼠 A3 受体的亲和力。该衍生物包含在强效非选择性激动剂 1-(6-amino-9H-purin-9-yl)-1-deoxy-N-ethyl-beta-D-ribofuranuronamide++ (NECA) 中发现的 5' 取代基。虽然甲酰胺衍生物 (9-13) 对 A1 受体表现出亲和力，但尿素衍生物 (30-45) 对 A3 腺苷受体亚型表现出不同程度的亲和力和选择性。特别是在 6 位带有对磺酰氨基苯基脲的衍生物，与参考化合物 1-
• Synthesis of [1,2-3H]ethylamine hydrochloride and [3H]-labeled apadenoson for a human ADME study
  作者：Yang Hong、Samuel J. Bonacorsi、Yuan Tian、Sharon Gong、Donglu Zhang、W. Griffith Humphreys、Balu Balasubramanian、Edward H. Cheesman、Zhiqin Zhang、James F. Castner、Paul D. Crane

  DOI：10.1002/jlcr.1495

  日期：2008.2

  Tritium-labeled [1,2-3H]ethylamine hydrochloride was prepared through a multiple-step sequence in high radioactive specificity. The labeled amine was isolated in high purity following cartridge filtration and used subsequently in the synthesis of [N-ethyl-1,2-3H]apadenoson, an adenosine A2a receptor agonist. The overall yield for this transformation was 56% and the radiochemical purity of the final product was greater than 99%. Copyright © 2008 John Wiley & Sons, Ltd.

  氚标记的[1,2-3H]乙胺盐酸盐是通过高放射性特异性的多步序列制备的。经过滤芯过滤，分离出高纯度的标记胺，随后用于合成腺苷 A2a 受体激动剂 [N-ethyl-1,2-3H]apadenoson。这次转化的总收率为 56%，最终产物的放射化学纯度超过 99%。Copyright © 2008 John Wiley & Sons, Ltd. All Rights Reserved.
• [EN] METHODS FOR PREPARING 2-ALKYNYLADENOSINE DERIVATIVES<br/>[FR] PROCEDES PERMETTANT DE PREPARER DES DERIVES DE 2-ALCYNYLADENOSINE
  申请人：BRISTOL MEYERS SQUIBB PHARMA C

  公开号：WO2004104017A3

  公开（公告）日：2005-03-24
• 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.