N6-(2-indanyl)adenosine | 96323-20-5

• 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: N6-(2-indanyl)adenosine
• 英文别名: N(6)-(2-indanyl)adenosine；(2R,3R,4S,5R)-2-[6-(2,3-dihydro-1H-inden-2-ylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 96323-20-5
• 化学式: C₁₉H₂₁N₅O₄
• 分子量: 383.407
• InChiKey: NKTIWTYWGRTWOE-NVQRDWNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2-氨基茚 、 6-氯嘌呤核苷 在 三乙胺 作用下， 以 乙醇 为溶剂， 生成 N6-(2-indanyl)adenosine
  参考文献：
  名称：

  N6-Substituted adenosine receptor agonists: potential antihypertensive agents

  摘要：

  Adenosine is known to exert a wide range of pharmacological effects including hypotension. This effect of adenosine suggested that modified analogues of adenosine might provide useful antihypertensive agents. Thus, we prepared a series of novel N6-benzocycloalkyladenosines and studied their receptor binding and antihypertensive activity. The structure-activity relationship study shows that the adenosine analogues having the hydrophobic phenyl moiety one carbon away from the C6-nitrogen have modest affinity and selectivity for the A1 receptor, whereas those with the phenyl moiety two carbons away from the C6-nitrogen have excellent affinity and selectivity for the A1 receptor. Many of these analogues showed excellent antihypertensive activity with a wide range of effects on heart rate. There is no direct correlation between the receptor binding affinities and antihypertensive activity; however, it is more closely associated with A1 than A2 affinity. The bradycardic effect of these agonists seems to be due to the A1 affinity. From this set, compound 3 was further evaluated in secondary antihypertensive screens. It lowered the blood pressure dose dependently with effects lasting for over 20 h following administration of a 30 mg/kg dose. Compound 3 was also effective in lowering blood pressure in a renal hypertensive rat model. Thus, appropriately modified N6-substituted adenosines represent a novel class of antihypertensive agents.

  DOI：

  10.1021/jm00107a025

文献信息

• N6-(1- and 2-benzocycloalkyl) adenosines
  申请人：Warner-Lambert Company

  公开号：US04501735A1

  公开（公告）日：1985-02-26

  N.sup.6 -(1 and 2-Benzocycloalkyl)adenosines and pharmaceutically acceptable acid addition salts having highly desirable central nervous system and cardiovascular properties, process for their manufacture, pharmaceutical compositions and methods for using said compounds and compositions are described.

  描述了具有极具吸引力的中枢神经系统和心血管特性的N.sup.6 -(1和2-苯并环烷基)腺苷和药用可接受的酸盐，以及它们的制备方法、药物组合物和使用这些化合物和组合物的方法。
• Dog coronary artery adenosine receptor. Structure of the N6-aryl subregion
  作者：Shozo Kusachi、Robert D. Thompson、Noboyuki Yamada、Daniel T. Daly、R. A. Olsson

  DOI：10.1021/jm00156a016

  日期：1986.6

  Previous structure-coronary vasoactivity correlations of the N6-alkyladenosine analogues of N6-[(R)-1-phenyl-2-propyl]adenosine, 1, support the hypothesis that the coronary artery A2 adenosine receptor contains an N6 region of specialized structure. The part of this receptor region that binds the 2-propyl moiety of 1 determines stereoselectivity and contributes to coronary vasoactivity. The present study uses 92 adenosine analogues containing an aryl group in the N6 substituent to test the hypothesis that the N6 receptor region contains an aryl subregion that binds the phenyl moiety of 1 and thereby contributes to its coronary vasoactivity. N6-Aralkyladenosines are often more potent than their alkyl congeners. Two methylene residues seem to provide optimum separation of the aryl group from N6. Among adenosines with semirigid N6 substituents, N6-[(1R,2S)-trans-2-phenylcyclohexyl]adenosine was uniquely active, evidence that when 1 occupies the receptor, the axis of the propyl C-1 to phenyl C-1 bond is nearly in the plane described by N6 and propyl C-1 and C-2. The torsion angle around this bond is unknown. Replacing the phenyl group of N6-2-phenethyladenosine with a thienyl or a 3-pyridyl group raises activity. The structure-activity relationships of the N6-(arylethyl)-, the N6-(arylmethyl)-, and the N6-phenyladenosines differ strinkingly from each other. Taken together, such results support the idea that the N6 region of the dog coronary artery A2 adenosine receptor includes an aryl subregion.
• US4501735A
  申请人：——

  公开号：US4501735A

  公开（公告）日：1985-02-26
• N6-Substituted adenosine receptor agonists: potential antihypertensive agents
  作者：B. K. Trivedi、C. J. Blankley、J. A. Bristol、H. W. Hamilton、W. C. Patt、W. J. Kramer、S. A. Johnson、R. F. Bruns、D. M. Cohen、M. J. Ryan

  DOI：10.1021/jm00107a025

  日期：1991.3

  Adenosine is known to exert a wide range of pharmacological effects including hypotension. This effect of adenosine suggested that modified analogues of adenosine might provide useful antihypertensive agents. Thus, we prepared a series of novel N6-benzocycloalkyladenosines and studied their receptor binding and antihypertensive activity. The structure-activity relationship study shows that the adenosine analogues having the hydrophobic phenyl moiety one carbon away from the C6-nitrogen have modest affinity and selectivity for the A1 receptor, whereas those with the phenyl moiety two carbons away from the C6-nitrogen have excellent affinity and selectivity for the A1 receptor. Many of these analogues showed excellent antihypertensive activity with a wide range of effects on heart rate. There is no direct correlation between the receptor binding affinities and antihypertensive activity; however, it is more closely associated with A1 than A2 affinity. The bradycardic effect of these agonists seems to be due to the A1 affinity. From this set, compound 3 was further evaluated in secondary antihypertensive screens. It lowered the blood pressure dose dependently with effects lasting for over 20 h following administration of a 30 mg/kg dose. Compound 3 was also effective in lowering blood pressure in a renal hypertensive rat model. Thus, appropriately modified N6-substituted adenosines represent a novel class of antihypertensive agents.