N-<(3,4-dihydro-1-naphthalenyl)methyl>adenosine | 103791-32-8

• 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: N-<(3,4-dihydro-1-naphthalenyl)methyl>adenosine
• 英文别名: N-[(3,4-dihydro-1-naphthalenyl)methyl]adenosine；(2R,3R,4S,5R)-2-[6-(3,4-dihydronaphthalen-1-ylmethylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 103791-32-8
• 化学式: C₂₁H₂₃N₅O₄
• 分子量: 409.445
• InChiKey: BEPRQXGEYGEJMG-QTQZEZTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 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：

  1-氨基甲基-1,2,3,4-四氢-萘-1-醇 在 盐酸 、 三乙胺 作用下， 以 乙醇 、 水 为溶剂， 反应 72.0h， 生成 N-<(3,4-dihydro-1-naphthalenyl)methyl>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-substituted adenosines
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0179667A2

  公开（公告）日：1986-04-30

  There is disclosed a compound of the following general formula (I): its diastereomer, or a pharmaceutically acceptable acid addition salt thereof; wherein R1 is of the formula or in which; n is an integer of from one to four; Z is hydrogen, lower alkyl or hydroxy; Y is hydrogen, lower alkyl, or OR where R is hydrogen, lower alkyl or lower alkanoyl; A is a bond or a straight or branched alkylene of from one to four carbon atoms, with the proviso that A cannot be a bond when R1 is of Formula II and n is one; X and X' are each, independently, hydrogen, lower alkyl, lower alkoxy, hydroxy, lower alkanoyl, nitro, trifluoromethyl, halogen, amino, monolower-alkyl or diloweralkylamino, or when taken X and X' together are a methylenedioxy group; R2 is a) hydrogen, b) halogen, c) NR'R" where R' and R" are independently hydrogen, lower alkyl, phenyl, or phenyl substituted by lower alkyl, lower alkoxy, halogen, or trifluoromethyl, d) SR'" where R" is hydrogen, lower alkyl, lower alkanoyl, benzoyl, or phenyl; R'2, R'3 and R'e are each, independently, hydrogen, alkanoyl having two to twelve carbon atoms, inclusive, in a straight or branched alkyl chain, benzoyl, or benzoyl substituted by lower alkyl, lower alkoxy, halogen, or R'2 and R'3 taken together are a five- membered ring having a total of up to twenty carbons; or R'e is, independently, a phosphate, hydrogen, or dihydrogen phosphate, or an alkali metal or ammonium, or dialkali or diammonium salt thereof; with the proviso that overall when R1 is II and X' X', Y, and Z are hydrogen, or lower alkyl then n cannot be two. The novel N6-substituted adenosines have desirable ratio of affinities at A1 or A2 receptors and highly desirable central nervous system and cardiovascular activities, such as analgesic, antipsychotic, sedative, or antihypertensive as well as immunoinflammatory activity.

  本发明公开了一种通式（I）如下的化合物： 其非对映异构体，或其药学上可接受的酸 加成盐； 其中 R1 为式 或 其中 n 是 1 到 4 的整数； Z 是氢、低级烷基或羟基； Y 是氢、低级烷基或 OR，其中 R 是氢、低级烷基或低级烷酰基； A 是键或 1 至 4 个碳原子的直链或支链亚烷基，但当 R1 为式 II 且 n 为 1 时，A 不能为键； X和X'各自独立地为氢、低级烷基、低级烷氧基、羟基、低级烷酰基、硝基、三氟甲基、卤素、氨基、单低级烷基或稀低烷基氨基，或当X和X'合在一起时为亚甲基二氧基； R2 是 a) 氢，b) 卤素，c) NR'R"，其中 R' 和 R "独立地是氢、低级烷基、苯基或被低级烷基、低级烷氧基、卤素或三氟甲基取代的苯基，d) SR'"，其中 R" 是氢、低级烷基、低级烷酰基、苯甲酰基或苯基； R'2、R'3 和 R'e 各自独立地是氢、在直链或支链烷基中具有 2 至 12 个碳原子的烷酰基、苯甲酰基或被低级烷基、低级烷氧基、卤素取代的苯甲酰基，或 R'2 和 R'3 合在一起是一个总碳数不超过 20 个的五元环；或 R'e 独立地是磷酸、氢或磷酸二氢、或碱金属或铵、或二碱或二铵盐；但总体上，当 R1 是 II 且 X' X'、Y 和 Z 是氢、或低级烷基时，则 n 不能为 2。 新型 N6 取代腺苷在 A1 或 A2 受体上具有理想的亲和力比率，并具有非常理想的中枢神经系统和心血管活性，如镇痛、抗精神病、镇静或抗高血压以及免疫炎症活性。
• TRIVEDI, BHARAT K.;MOOS, WALTER;HAMILTON, HARRIET W.;PATT, WILLIAM C.
  作者：TRIVEDI, BHARAT K.、MOOS, WALTER、HAMILTON, HARRIET W.、PATT, WILLIAM C.

  DOI：——

  日期：——
• 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.