(2S,3S,4R,5R)-5-(6-氨基-2-己-1-炔基嘌呤-9-基)-N-乙基-3,4-二羟基四氢呋喃-2-甲酰胺 | 141018-30-6

• 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: (2S,3S,4R,5R)-5-(6-氨基-2-己-1-炔基嘌呤-9-基)-N-乙基-3,4-二羟基四氢呋喃-2-甲酰胺
• 英文名称: HE-NECA
• 英文别名: HENECA；N-ethyl-1'-deoxy-1'-(6-amino-2-hexynyl-9H-purin-9-yl)-β-D-ribofuranuronamide；2-hexynyl-5’-N-ethylcarboxamidoadenosine；2-(1-hexyn-1-yl)adenosine-5'-N-ethyluronamide；2-hexynyl-5'-(N-ethyl-carboxamido)adenosine；2-HE-NECA；2-Hexynyl-NECA；(2S,3S,4R,5R)-5-(6-amino-2-hex-1-ynylpurin-9-yl)-N-ethyl-3,4-dihydroxyoxolane-2-carboxamide
• CAS: 141018-30-6
• 化学式: C₁₈H₂₄N₆O₄
• 分子量: 388.426
• InChiKey: FDEACFAXFCKCHZ-MOROJQBDSA-N

物化性质

• 熔点：
  135-140°C
• 密度：
  1.49±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：20 毫克/毫升

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 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：

  (2S,3S,4R,5R)-5-(6-氨基-2-己-1-炔基嘌呤-9-基)-N-乙基-3,4-二羟基四氢呋喃-2-甲酰胺 在 Lindlar's catalyst 喹啉 、 氢气 作用下， 以 丙酮 为溶剂， 反应 9.0h， 以75%的产率得到(2S,3S,4R,5R)-5-[6-amino-2-[(Z)-hex-1-enyl]purin-9-yl]-N-ethyl-3,4-dihydroxyoxolane-2-carboxamide
  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：

  2',3'-O-isopropylidene-2-(1-hexyn-1-yl)adenosine-5'-N-ethyluronamide 在 三氟乙酸 作用下， 反应 2.0h， 以86%的产率得到(2S,3S,4R,5R)-5-(6-氨基-2-己-1-炔基嘌呤-9-基)-N-乙基-3,4-二羟基四氢呋喃-2-甲酰胺
  参考文献：
  名称：

  核苷和核苷酸。112. 2-（1-己基-1-基）腺苷-5'-脲酰胺：具有有效降压活性的选择性A2腺苷受体激动剂的新进入。

  摘要：

  已经进行了在5'-位上的有效A2腺苷受体激动剂2-（1-己炔-1-基）腺苷（7，2-HA）的化学修饰，以发现更有效和选择性的A2激动剂。对这些类似物在大鼠脑组织中的腺苷A1和A2受体结合亲和力以及自发性高血压大鼠（SHR）的降压作用进行了评估。在这一系列化合物中，2-（1-己炔-1-基）腺苷-5'-N-环丙基脲酰胺（16d）对A2受体的亲和力最强，Ki为2.6 nM，与亲本激动剂2-HA 但是，对A2受体最具选择性的激动剂是2-（1-己炔-1-基）腺苷-5'-N-甲基脲酰胺（16b），Ki为11 nM，选择性为162倍。5'的N-烷基取代基 与母体2-HA相比，-uronamide衍生物似乎没有增强A2结合亲和力，但大大降低了A1亲和力。因此，因此提高了A1 / A2的选择性。还制备了2-HA的其他5'-脱氧-5'-取代的衍生物，例如氯（20），羧酰胺（27、28），磺酰胺（29），脲（3

  DOI：

  10.1021/jm00093a022

文献信息

• 2-Alkynyl derivatives of adenosine and adenosine-5'-N-ethyluronamide as selective agonists at A2 adenosine receptors
  作者：Gloria Cristalli、Alessandra Eleuteri、Sauro Vittori、Rosaria Volpini、Martin J. Lohse、Karl Norbert Klotz

  DOI：10.1021/jm00091a003

  日期：1992.6

  binding at solubilized A2 receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [3H]DPCPX and for the agonist [3H]CCPA gave Ki values in the nanomolar range, and the compounds showed moderate A2 selectivity. In order to improve this selectivity, the corresponding 2-alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and

  在寻找更具选择性的A2受体激动剂的过程中，并基于已知在C2处进行适当的取代可以赋予A2受体选择性的方法，重新合成了2炔基腺苷2a-d，并进行了放射性配体结合，腺苷酸环化酶和血小板聚集研究。化合物2a-d抑制了[3H] NECA与大鼠纹状体膜的A2受体的结合，Ki值为2.8至16.4 nM。2-炔基腺苷在人血小板膜的可溶性A2受体上也表现出高亲和力结合。2-炔基腺苷2a-d与拮抗剂放射性配体[3H] DPCPX和激动剂[3H] CCPA的竞争给出Ki值在纳摩尔范围内，并且这些化合物显示出中等的A2选择性。为了提高这种选择性，相应的腺苷5'的2-炔基衍生物 合成并测试了-N-乙基脲酰胺8a-d。正如预期的那样，5'-N-乙基脲酰胺衍生物保留了A2亲和力，而A1亲和力却减弱了，导致A2选择性提高了10倍。在腺苷酸环化酶测定和血小板聚集研究中观察到相似的模式。在腺苷酸环化酶研究中，对于化合物8a-
• MEDICINAL COMPOSITION FOR PREVENTION OR TREATMENT OF HEPATOPATHY
  申请人：Nippon Shinyaku Co., Ltd.

  公开号：EP0983768A1

  公开（公告）日：2000-03-08

  A medicinal composition containing an adenosine A2 receptor agonist as the active ingredient. It is effective in the prevention or treatment of hepatopathy.

  一种以腺苷 A2 受体激动剂为活性成分的药物组合物。它可有效预防或治疗肝病。
• 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).
• Linear and convergent approaches to 2-substituted adenosine-5′-N-alkylcarboxamides
  作者：Richard C. Foitzik、Shane M. Devine、Nicholas E. Hausler、Peter J. Scammells

  DOI：10.1016/j.tet.2009.08.057

  日期：2009.10

  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.
• SMALL MOLECULE CELLULAR REPROGRAMMING TO GENERATE NEURONAL CELLS
  申请人：The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone

  公开号：EP3039126A2

  公开（公告）日：2016-07-06