5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-甲酰胺 | 35788-21-7

• 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: 5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-甲酰胺
• 英文名称: adenosine 5'-carboxamide
• 英文别名: 1-(aden-9-yl)-1-deoxy-β-D-ribofuranuronamide；1-(6-amino-purin-9-yl)-β-D-1-deoxy-ribofuranuronic acid amide；Adenosin-5'-carboxamid；(2S,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide
• CAS: 35788-21-7
• 化学式: C₁₀H₁₂N₆O₄
• 分子量: 280.243
• InChiKey: BLMHAOGGJQDPLX-LKCKTBJASA-N

物化性质

• 沸点：
  422.96°C (rough estimate)
• 密度：
  1.3705 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  162
• 氢给体数：
  4
• 氢受体数：
  8

制备方法与用途

类别：有毒物品

毒性分级：剧毒

急性毒性：

• 口服（小鼠）LD50：50毫克/公斤
• 腹腔（小鼠）LD50：5毫克/公斤

可燃性危险特性：

• 明火可燃
• 高温分解，燃烧时释放有毒氮氧化物烟雾

储运特性：

• 库房应通风、低温干燥
• 与氧化剂及食品添加剂分开存放

灭火剂：

• 二氧化碳
• 泡沫
• 干粉
• 砂土
• 雾状水

反应信息

• 作为反应物：
  描述：

  5-(6-氨基嘌呤-9-基)-3,4-二羟基四氢呋喃-2-甲酰胺 在 E_. coli purine nucleoside phosphorylase 作用下， 生成 腺嘌呤 、
  参考文献：
  名称：

  Gene Therapy of Cancer: Activation of Nucleoside Prodrugs withE. coliPurine Nucleoside Phosphorylase

  摘要：

  During the last few years, many gene therapy strategies have been developed for various disease targets. The development of anticancer gene therapy strategies to selectively generate cytotoxic nucleoside or nucleotide analogs is an attractive goal. One such approach involves the delivery of herpes simplex virus thymidine kinase followed by the acyclic nucleoside analog ganciclovir. We have developed another gene therapy methodology for the treatment of cancer that has several significant attributes. Specifically, our approach involves the delivery off. coli purine nucleoside phosphorylase, followed by treatment with a relatively non-toxic nucleoside prodrug that is cleaved by the enzyme to a toxic compound. This presentation describes the concept, details our search for suitable prodrugs, and summarizes the current biological data.

  DOI：

  10.1080/15257779908041562
• 作为产物：
  描述：

  2',3'-isopropylideneadenosine-5'-carboxylic acid 在 氨 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 5-(6-氨基嘌呤-9-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。200. 5'-N-乙基羧酰胺基腺苷衍生物的再研究：P（3）嘌呤受体样蛋白的结构-活性关系。

  摘要：

  ATP在兔胸主动脉中的非P（1）和非P（2）肌肉松弛作用最近归因于推定的P（3）嘌呤受体，该受体被腺苷或ATP激活。由于此假定的P（3）嘌呤受体和新的[（3）H] -5'-N-乙基羧酰胺基腺苷（NECA）结合蛋白从大鼠脑膜的生理作用，称为P（3）嘌呤受体样蛋白（P （3）LP），由于其配体特异性尚未完全阐明，我们需要特定的配体以获得有关受体的进一步信息。我们检查了各种5'-N-取代的羧酰胺基腺苷衍生物对P（3）LP的结构-活性关系（SAR），并发现了5'-N-取代的羧酰胺基附近的疏水结合区。从直链烷基N-取代的衍生物，Nn-戊基衍生物10被发现是最有效的配体，其K（i）值为12 nM。在一系列N-环烷基衍生物中，N-环己基衍生物27是最强的配体，其K（i）值为18 nM。另一方面，具有支链烷基侧链和庞大的环烷基的N-取代基对P（3）LP没有任何有效的亲和力。因此，疏水口袋容纳大约10个碳原

  DOI：

  10.1021/jm000150k

文献信息

• Modification of the 5' position of purine nucleosides. 2. Synthesis and some cardiovascular properties of adenosine-5'-(N-substituted)carboxamides
  作者：Raj Nandan Prasad、Dilbagh S. Bariana、Anthony Fung、Milica Savic、Karin Tietje、Herman H. Stein、Harold Brondyk、Richard S. Egan

  DOI：10.1021/jm00177a021

  日期：1980.3

  of the esters of adenosine-5'-carboxylic acid, a systematic study of the corresponding amides (14--50) was undertaken. In addition, several other analogues containing the N1-oxide function (51--52) or 2',3' substituents (3--9, 53--54) were studied.

  先前我们已经表明，腺苷5'-羧酸酯（10）代表了一类新的有效的无毒冠状血管扩张剂。例如，在犬中通过十二指肠内或静脉内途径具有活性的乙酯（12）会导致冠状窦PO2和冠状动脉血流大量增加。由于腺苷5'-羧酸的酯具有明显的血管活性，因此对相应的酰胺（14--50）进行了系统的研究。此外，还研究了其他几种含有N1-氧化物官能团（51--52）或2'，3'取代基（3--9、53--54）的类似物。
• N6-Substituted N-alkyladenosine-5'-uronamides: bifunctional ligands having recognition groups for A1 and A2 adenosine receptors
  作者：R. A. Olsson、Shozo Kusachi、Robert D. Thompson、Dieter Ukena、William Padgett、John W. Daly

  DOI：10.1021/jm00159a020

  日期：1986.9

  The coronary vasoactivity of N-ethyl-1'-deoxy-1'-(6-amino-9H-purin-9-yl)-beta-D-ribofuranuronamide (NECA, 1) is over 2 orders of magnitude greater than that of adenosine, and the vasoactivity of certain N6-substituted adenosines is as much as 1 order of magnitude greater. Such results suggest that a combination of appropriate modifications at N6 and C-5' might additively augment the agonist potency of adenosine. At low temperatures 1-deoxy-1-(6-chloro-9H-purin-9-yl)-2',3'-O-isopropylidene- beta-D-ribofuranosyl chloride (5), obtained in three steps from inosine, reacts with amines to yield uronamides. The subsequent reaction of such uronamides with amines at elevated temperatures displaces the purine 6-chloro group to yield, after deblocking, N-alkyl(or aryl)-N6-alk(ar)yl-adenosine-5'-uronamides. At the coronary artery A2 receptor the potency of N6-modified analogues of 1 is similar to that of the N6-substituted adenosine, rather than equal to or greater than 1. As agonists in the A2 receptor-mediated stimulation of adenylate cyclase in plasma membranes of PC12 pheochromocytoma cells or human platelets, N6-substituted analogues of 1 are intermediate between the high potency of 1 and the lower potency of the N6-substituted adenosines. At the A1 receptor of rat brain the potency of an N6-substituted analogue of 1 is often greater than that of the corresponding N6-substituted adenosine. At all four receptors, replacing the ethyl group of N-ethyl-N6-3-pentyladenosine-5'-uronamide by larger alkyl groups reduces potency; amides of secondary amines are inactive or have only marginal activity. Analogues of 1 containing a chiral center in the N6 substituent retain the stereoselectivity characteristic of each of the four receptors. Thus, at either A1 or A2 adenosine receptors, adenosine analogues interact with both the N6 and the C-5' receptor regions. However, the effects of N6 and C-5' modifications on potency are less than additive, evidence that the interaction of a substituent with its receptor region influences the interaction of other substituents with their respective receptor regions.
• Structure-Activity Relationships of N6-Benzyladenosine-5'-uronamides as A3-Selective Adenosine Agonists
  作者：Carola Gallo-Rodriguez、Xiao-duo Ji、Neli Melman、Barry D. Siegman、Lawrence H. Sanders、Jeraldine Orlina、Bilha Fischer、Quanlong Pu、Mark E. Olah

  DOI：10.1021/jm00031a014

  日期：1994.3

  Adenosine analogues modified at the 5'-position as uronamides and/or as N-6-benzyl derivatives were synthesized. These derivatives were examined for affinity in radioligand binding assays at the newly discovered rat brain A(3) adenosine receptor and at rat brain A(1) and Az, receptors. 5'Uronamide substituents favored AS selectivity in the order N-methyl > N-ethyl approximate to unsubstituted carboxamide > N-cyclopropyl. 5'-(N-Methylcarboxamido)-N-6-benzyladenosine was 37-56-fold more selective for Ag receptors. Potency at A(3) receptors was enhanced upon substitution of the benzyl substituent with nitro and other groups. 5'-N-Methyluronamides and N-6-(3-substituted-benzyl) adenosines are optimal for potency and selectivity at A(3) receptors. A series of 3-(halobenzyl)5'-N-ethyluronamide derivatives showed the order of potency at A(1) and A(2)a receptors of I similar to Br > Cl > F. At A(3) receptors the 3-F derivative was weaker than the other halo derivatives. 5'-N-Methyl-N-6- (3-iodobenzyl) adenosine displayed a K-i value of 1.1 nM at A(3) receptors and selectivity versus A(1) and A(2a), receptors of 50-fold. A series of methoxybenzyl derivatives showed that a C-methoxy group best favored A(3) selectivity. A 4-sulfobenzyl derivative was a specific ligand at A(3) receptors of moderate potency. An aryl amino derivative was prepared as a probe for radioiodination and receptor cross-linking.
• Inactivation of <i>S-</i>Adenosyl-<scp>l</scp>-homocysteine Hydrolase by Amide and Ester Derivatives of Adenosine-5‘-carboxylic Acid
  作者：Stanislaw F. Wnuk、Siming Liu、Chong-Sheng Yuan、Ronald T. Borchardt、Morris J. Robins

  DOI：10.1021/jm960313y

  日期：1996.1.1

  S-Adenosyl-L-homocysteine (AdoHcy) hydrolase has been shown to have (5'/6') hydrolytic activity with vinyl (5') or homovinyl (6') halides derived from adenosine (Ado). This hydrolytic activity is independent of its 3'-oxidative activity. The vinyl (or homovinyl) halides are converted into 5'(or 6')-carboxaldehydes by the hydrolytic activity of the enzyme, and inactivation occurs via the oxidative activity. Amide and ester derivatives of Ado-5'-carboxylic acid were prepared to further probe the hydrolytic capability of AdoHcy hydrolase. The oxidative activity (but not the hydrolytic activity) is involved in the mechanism of inhibition of the enzyme by the ester and amide derivatives of Ado-5'-carboxylic acid, in contrast to the inactivation of this enzyme by adenosine-derived vinyl or homovinyl halide analogues during which both activities are manifested.
• HIGH CONTENT SCREENING
  申请人：Hill Stephen John

  公开号：US20090093001A1

  公开（公告）日：2009-04-09

  A high content screening (HCS) assay for rapidly screening one or more compounds to determine functional response or pharmacological properties thereof, comprising: i) priming a cell or cell material with a sensor for a biological response; ii) contacting the compound(s) to be tested with the primed cell or cell material or contacting a cell or cell material which has been contacted with the compound(s) with the primed cell or cell material; iii) simultaneously or subsequently contacting with a fluorescent agonist or a fluorescent neutral antagonist wherein the binding of the fluorescent agonist or antagonist and its associated biological response are detected or monitored in the same cell and are distinct allowing separate readout.