(3aS,4S,6R,6aR)-6-[6-Amino-2-(3-hydroxy-3-phenyl-prop-1-ynyl)-purin-9-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethylamide | 203794-21-2

• 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: (3aS,4S,6R,6aR)-6-[6-Amino-2-(3-hydroxy-3-phenyl-prop-1-ynyl)-purin-9-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethylamide
• CAS: 203794-21-2
• 化学式: C₂₄H₂₆N₆O₅
• 分子量: 478.508
• InChiKey: YDMLKPFSCANXGQ-GYYCOEDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.05
• 重原子数：
  35.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  146.64
• 氢给体数：
  3.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  (3aS,4S,6R,6aR)-6-[6-Amino-2-(3-hydroxy-3-phenyl-prop-1-ynyl)-purin-9-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethylamide 在 三氟乙酸 作用下， 生成 PHPNECA
  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
• 作为产物：
  描述：

  2-iodo NECA 在 bis-triphenylphosphine-palladium(II) chloride 氢氧化钾 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (3aS,4S,6R,6aR)-6-[6-Amino-2-(3-hydroxy-3-phenyl-prop-1-ynyl)-purin-9-yl]-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid ethylamide
  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

• Adenosine receptor agonists: Synthesis and biological evaluation of the diastereoisomers of 2-(3-hydroxy-3-phenyl-1-propyn-1-yl)NECA
  作者：Emidio Camaioni、Emanuela Di Francesco、Sauro Vittori、Rosaria Volpini、Gloria Cristalli

  DOI：10.1016/s0968-0896(97)00172-7

  日期：1997.12

  Among the recently reported 2-(ar) alkynyl derivatives of 5'-N-ethylcarboxamidoadenosine (NECA), the (R,S)-2-(3-hydroxy-3-phenyl-1-propyn-1-yl)NECA [(R,S)-PHPNECA or SCH 59761] was found to be a very potent agonist at A(1) and A(2A) receptor subtypes, with a K-i of 2.5 nM and 0.9 nM, respectively. Furthermore, this compound showed an inhibitory activity on platelet aggregation 16-fold higher than NECA, being the most potent anti-aggregatory nucleoside reported so far. Since this compound bears a chiral carbon in the side chain, the diastereoisomer separation was undertaken both by chiral HPLC and by a stereospecific synthetic method. Binding assays have shown that the (S)-diastereomer is about fivefold more potent and selective than the (R)-diastereomer as agonist of the A(2A) receptor subtype [(S)-PHPNECA, K(i)A(2A) = 0.5 nM; (R)-PHPNECA, K(i)A(2A) = 2.6 nM]. Functional studies indicated that (S)-PHPNECA possesses marked vasodilating activity and produces a relevant decrease in heart rate. Moreover, the (S)-diastereomer proved to be about ten times more potent than the (R)-diastereomer in inducing cardiovascular effects, in in vivo hemodynamic studies. However, the greatest difference between these two enantiomers resulted in the platelet aggregation test: in fact, the (R)-diastereomer displayed an inhibitory activity similar to that of NECA, whereas the (S)-diastereomer was 37-fold more active than NECA as an inhibitor of rabbit platelet aggregation, induced by ADP. These data suggest that (S)-PHPNECA could be a useful tool to investigate the mode of binding of agonists to the platelet adenosine receptor subtype. (C) 1997 Elsevier Science Ltd.