2-辛炔基腺苷 | 90596-75-1

• 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-辛炔基腺苷
• 中文别名: 2(1H)-吡啶酮,3-羟基-1-(1-甲基乙基)-
• 英文名称: YT-146
• 英文别名: 2-(1-octyn-1-yl)adenosine；YT 146；2-octynyladenosine；2-(1-octynyl)adenosine；(2R,3R,4S,5R)-2-(6-amino-2-oct-1-ynylpurin-9-yl)-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 90596-75-1
• 化学式: C₁₈H₂₅N₅O₄
• 分子量: 375.428
• InChiKey: NVGGIHKSKVAPEY-XKLVTHTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  140
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-辛炔基腺苷 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 7.0h， 以60%的产率得到2-(1-octyn-1-yl)adenine
  参考文献：
  名称：

  核苷和核苷酸。103. 2-炔基腺苷：具有有效降压作用的新型一类选择性腺苷A2受体激动剂。

  摘要：

  描述了一系列2-炔基腺苷在A1和A2腺苷受体上的合成和受体结合活性。在含三乙胺的N，N-二甲基甲酰胺中，在双（三苯基膦）二氯化钯和碘化亚铜的存在下，钯催化的2-碘腺苷（4a）与各种末端炔的交叉偶联反应生成2-炔基腺苷（5a-r）。一种经济的合成方法，用于制备9a（2,3,5-三-O-乙酰基-1-β-D-呋喃呋喃糖基）-6-氯-2-碘代嘌呤++ +（2），这是4a的前体，也包括在内。2-（1-辛炔-1-基）腺苷（5e）和2-（1-乙炔-1-基）腺苷（9）的几种转化反应以及6-氯嘌呤衍生物11和8的相似交叉偶联反应还报道了带有1-辛炔的-溴腺苷（13）。在大鼠脑中针对A1和A2腺苷受体结合活性进行测试的许多这类2-炔基腺苷对A2腺苷受体具有选择性。其中，2-（1-己炔-1-基）腺苷（5c）对A1和A2受体的亲和力最高，Ki值分别为126.5和2.8 nM。讨论了这一系列化合物的结构活性关系，包

  DOI：

  10.1021/jm00080a007
• 作为产物：
  描述：

  1-辛炔 在 bis-triphenylphosphine-palladium(II) chloride 、 ammonium hydroxide 、 copper(l) iodide 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 22.0h， 生成 2-辛炔基腺苷
  参考文献：
  名称：

  Nucleosides and nucleotides. 107. 2-(Cycloalkylalkynyl)adenosines: adenosine A2 receptor agonists with potent antihypertensive effects

  摘要：

  Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (K(i) ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100-mu-g/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3" position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.

  DOI：

  10.1021/jm00090a017

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-
• NOVEL 2-ALKYNYL-N9-PROPARGYLADENINE AND MEDICINAL USE THEREOF
  申请人：Endo Kazuki

  公开号：US20130245046A1

  公开（公告）日：2013-09-19

  In the present invention, a novel 2-alkynyl-N9-propargyladenine represented by formula (I) wherein R 1 represents a halogen atom, a furyl group, or a triazolyl group; R 2 and R 3 each represents a hydrogen atom or a C1-8 alkyl group, or form a cycloalkyl group by bonding to each other; and X represents a hydrogen atom or a hydroxyl group, or a pharmaceutically acceptable salt thereof, has a stronger and longer-lasting effect as a therapeutic agent for Parkinsonian syndromes.

  本发明涉及一种新型2-炔基-N9-丙炔基腺嘌呤，其化学式为（I），其中R1代表卤素原子、呋喃基或三唑基；R2和R3分别代表氢原子或C1-8烷基，或通过相互结合形成环烷基；X代表氢原子或羟基，或其药学上可接受的盐。该化合物作为帕金森综合症治疗剂具有更强和更持久的效果。
• Adenosine derivatives and use thereof
  申请人：Konno Takashi

  公开号：US20050130930A1

  公开（公告）日：2005-06-16

  2-(6-Cyano-1-hexyn-1-yl)adenosine, 2-(6-cyano-1-hexyn-1-yl)adenosine 5′-monophosphate, or salts thereof; and drugs containing the same as an active ingredient. The compounds have excellent effects of lowering ocular tension, promoting blood flow in retina, and protecting optic nerve failure and are highly soluble in water. Owing to these characteristics, the compounds are useful as drugs such as remedies for glaucoma and ocular hypertension.

  2-(6-氰基-1-己炔-1-基)腺苷、2-(6-氰基-1-己炔-1-基)腺苷5'-磷酸或其盐；以及含有其作为活性成分的药物。这些化合物具有降低眼压、促进视网膜血流、保护视神经功能失调的优异效果，并且在水中高度溶解。由于这些特性，这些化合物可用作药物，例如治疗青光眼和眼内压的药物。
• Pyrazine Derivatives Useful as Adenosine Receptor Antagonists
  申请人：Vidal Juan Bernat

  公开号：US20090042891A1

  公开（公告）日：2009-02-12

  The present disclosure relates to a compound of formula (I) wherein: A is an optionally substituted monocyclic or polycyclic aryl or heteroaryl group; B is an optionally substituted monocyclic nitrogen-containing heteroaryl group; and either a) R 1 and R 2 are chosen from a hydrogen atom and specified substituents, or b) R 2 , R 1 and the —NH— group to which R 1 is attached, form a moiety chosen from the moiety of formulae (IIa) and (IIb): or a pharmaceutically acceptable salt thereof, or a N-oxide thereof. The present disclosure also relates to a method for treating a subject afflicted with a pathological condition or disease susceptible to amelioration by antagonism of the A 2B adenosine receptor.

  本公开涉及一种式（I）的化合物，其中：A是可选取的取代的单环或多环芳基或杂芳基基团；B是可选取的取代的单环含氮杂芳基基团；并且要么a）R1和R2选择自氢原子和指定的取代基，要么b）R2、R1和R1附着的—NH—基团形成式（IIa）和（IIb）的基团：或其药学上可接受的盐或其N-氧化物。本公开还涉及一种治疗患有病理状况或疾病，易于通过拮抗A2B腺苷受体而改善的受试者的方法。
• PYRAZINE DERIVATIVES USEFUL AS ADENOSINE RECEPTOR ANTAGONISTS
  申请人：Vidal Juan Bernat

  公开号：US20100273757A1

  公开（公告）日：2010-10-28

  The present invention provides a compound of formula (I) wherein: A represents an optionally substituted monocyclic or polycyclic aryl or heteroaryl group B represents an optionally substituted monocyclic nitrogen-containing heteroaryl group; and either a) R 1 and R 2 represent hydrogen or specified substituents, or b) R 2 , R 1 and the —NH— group to which R 1 is attached, form a moiety selected from the moiety of formulae (IIa) and (IIb): (IIa) These compounds are useful as antagonists of the A2B receptor, for instance in the treatment of asthma.

  本发明提供了一种式为（I）的化合物，其中：A代表可选取代的单环或多环芳基或杂芳基基团；B代表可选取代的单环含氮杂芳基基团；并且要么a）R1和R2代表氢或指定的取代基，要么b）R2，R1和R1连接的—NH—基团形成从式（IIa）和（IIb）中选择的基团：（IIa）这些化合物可用作A2B受体拮抗剂，例如在哮喘治疗中。