5'-N-[(2-Amino)ethyl Carboxamido] Adenosine | 66822-83-1

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 5'-N-[(2-Amino)ethyl Carboxamido] Adenosine
• 英文别名: (2S,3S,4R,5R)-N-(2-aminoethyl)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolane-2-carboxamide
• CAS: 66822-83-1
• 化学式: C₁₂H₁₇N₇O₄
• 分子量: 323.311
• InChiKey: XZUQLQNOMFGRFJ-FLNNQWSLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  174
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  二碳酸二叔丁酯 、 5'-N-[(2-Amino)ethyl Carboxamido] Adenosine 以42%的产率得到(2-{[(2S,3S,4R,5R)-5-(6-Amino-purin-9-yl)-3,4-dihydroxy-tetrahydro-furan-2-carbonyl]-amino}-ethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Structure-Activity Relationships of N6-Benzyladenosine-5'-uronamides as A3-Selective Adenosine Agonists

  摘要：

  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.

  DOI：

  10.1021/jm00031a014
• 作为产物：
  描述：

  2',3'-isopropylideneadenosine-5'-carboxylic acid 在 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'-N-[(2-Amino)ethyl Carboxamido] Adenosine
  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

• 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.
• Nucleosides and Nucleotides. 200. Reinvestigation of 5‘-<i>N</i>-Ethylcarboxamidoadenosine Derivatives:  Structure−Activity Relationships for P₃ Purinoceptor-like Proteins
  作者：Takashi Umino、Kazuaki Yoshioka、Yoshiko Saitoh、Noriaki Minakawa、Hiroyasu Nakata、Akira Matsuda

  DOI：10.1021/jm000150k

  日期：2001.1.1

  protein (P(3)LP), due to its ligand specificity, have not been fully elucidated, we needed a specific ligand to obtain further information about the receptor. We examined the structure-activity relationship (SAR) of various 5'-N-substituted-carboxamidoadenosine derivatives toward P(3)LP and discovered a hydrophobic binding region near the 5'-N-substituted-carboxamide group. From the linear alkyl N-substituted

  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