1-异喹啉甲腈,2-苯甲酰-6,7-二氯-1,2-二氢-1-[(3,4,5-三甲氧苯基)甲基]- | 103959-62-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 中文名称: 1-异喹啉甲腈,2-苯甲酰-6,7-二氯-1,2-二氢-1-[(3,4,5-三甲氧苯基)甲基]-
• 英文名称: 2-benzoyl-6,7-dichloro-1-cyano-1-(3,4,5-trimethoxybenzyl)-1,2-dihydroisoquinoline
• 英文别名: 2-benzoyl-1-(3,4,5-trimethoxybenzyl)-6,7-dichloro-1-cyano-1,2-dihydroisoquinoline；2-benzoyl-6,7-dichloro-1-[(3,4,5-trimethoxyphenyl)methyl]isoquinoline-1-carbonitrile
• CAS: 103959-62-2
• 化学式: C₂₇H₂₂Cl₂N₂O₄
• 分子量: 509.389
• InChiKey: RBVVBJYOEVSATR-UHFFFAOYSA-N

物化性质

• 熔点：
  193-195 °C(Solv: acetonitrile (75-05-8))
• 沸点：
  683.0±55.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  71.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-异喹啉甲腈,2-苯甲酰-6,7-二氯-1,2-二氢-1-[(3,4,5-三甲氧苯基)甲基]- 在 sodium hydroxide 、 苄基三乙基氯化铵 作用下， 以 甲苯 为溶剂， 反应 1.5h， 生成 6,7-dichloro-1-(3,4,5-trimethoxybenzyl)isoquinoline
  参考文献：
  名称：

  6,7-Dichloro-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline. A structurally novel .beta.-adrenergic receptor blocking agent

  摘要：

  Replacement of the catecholic hydroxyl groups of the beta-adrenergic receptor agonist 6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (trimetoquinol) with chloro substituents results in a compound with marked beta-adrenoceptor antagonist properties. This, therefore, parallels the similar transformation of the beta-adrenoreceptor agonist isoproterenol into the antagonist dichloroisoproterenol. In a test for inhibition of isoproterenol-induced enhancement of the rate of contraction of spontaneously beating guinea pig atrial pairs the resultant 6,7-dichloro-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (6b) had a KB value of (6.7 +/- 2.3) X 10(-8) M. Although this is nearly 2 orders of magnitude less potent than propranolol (KB = 6.2 X 10(-10) M in this test), this compound represents the prototype of a new class of beta-adrenergic receptor blockers, and unlike dichloroisoproterenol it is not a partial agonist. It has physicochemical properties, e.g., pKa and distribution and partition coefficients, that differ from the prototypic beta-blockers. These altered properties might impart advantageous tissue distribution and altered pharmacological properties to the new molecule. This new beta-adrenoreceptor antagonist is suggested to merit further study.

  DOI：

  10.1021/jm00161a039
• 作为产物：
  描述：

  6,7-二氯-1,2,3,4-四氢异喹啉 在 sodium hydroxide 、 palladium on activated charcoal 、 18-冠醚-6 、 苄基三乙基氯化铵 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 21.5h， 生成 1-异喹啉甲腈,2-苯甲酰-6,7-二氯-1,2-二氢-1-[(3,4,5-三甲氧苯基)甲基]-
  参考文献：
  名称：

  6,7-Dichloro-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline. A structurally novel .beta.-adrenergic receptor blocking agent

  摘要：

  Replacement of the catecholic hydroxyl groups of the beta-adrenergic receptor agonist 6,7-dihydroxy-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (trimetoquinol) with chloro substituents results in a compound with marked beta-adrenoceptor antagonist properties. This, therefore, parallels the similar transformation of the beta-adrenoreceptor agonist isoproterenol into the antagonist dichloroisoproterenol. In a test for inhibition of isoproterenol-induced enhancement of the rate of contraction of spontaneously beating guinea pig atrial pairs the resultant 6,7-dichloro-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline (6b) had a KB value of (6.7 +/- 2.3) X 10(-8) M. Although this is nearly 2 orders of magnitude less potent than propranolol (KB = 6.2 X 10(-10) M in this test), this compound represents the prototype of a new class of beta-adrenergic receptor blockers, and unlike dichloroisoproterenol it is not a partial agonist. It has physicochemical properties, e.g., pKa and distribution and partition coefficients, that differ from the prototypic beta-blockers. These altered properties might impart advantageous tissue distribution and altered pharmacological properties to the new molecule. This new beta-adrenoreceptor antagonist is suggested to merit further study.

  DOI：

  10.1021/jm00161a039

文献信息

• Substituted te[1]trahydroisoquinoline derivatives having
  申请人：Smithkline Beckman Corporation

  公开号：US04707485A1

  公开（公告）日：1987-11-17

  Compounds having the formula ##STR1## are .beta.-adrenergic receptor antagonists. Also disclosed are pharmaceutical compositions and methods for producing .beta.-adrenergic receptor antagonistic activity in animals including man.

  具有##STR1##式的化合物是β-肾上腺素受体拮抗剂。还公开了用于在动物中包括人体内产生β-肾上腺素受体拮抗活性的药物组合物和方法。
• Substituted tetrahydro isoquinoline intermediates
  申请人：SmithKline Beckman Corporation

  公开号：US04767862A1

  公开（公告）日：1988-08-30

  Compounds having the formula ##STR1## are .beta.-adrenergic receptor antagonists. Also disclosed are pharmaceutical compositions and methods for producing .beta.-adrenergic receptor antagonistic activity in animals including man.

  具有公式## STR1##的化合物是β-肾上腺素能受体拮抗剂。还披露了制备β-肾上腺素能受体拮抗活性的动物，包括人类的制药组合物和方法。
• Tetrahydroisoquinoline derivatives, process and intermediates for their preparation and pharmaceutical compositions containing them
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0210827A2

  公开（公告）日：1987-02-04

  Compounds of structure (I) where Y is halogen, X, is C1-4 alkoxy, m is 0 to 4 and X2 is C1-4 alkoxy, halogen or C1 4alkyl, processes for their preparation, compositions containing them and their use as ß-adrenergic receptor antagonists.

  结构(I)的化合物 其中 Y 为卤素，X 为 C1-4 烷氧基，m 为 0 至 4，X2 为 C1-4 烷氧基、卤素或 C1-4 烷基的化合物、其制备方法、含有这些化合物的组合物以及它们作为ß-肾上腺素能受体拮抗剂的用途。
• KAISER C.; OH HYE-JA; GARCIA-SLANGA B. J.; SULPIZIO A. C.; HIEBLE J. P.; +, J. MED. CHEM., 29,(1986) N 11, 2381-2384
  作者：KAISER C.、 OH HYE-JA、 GARCIA-SLANGA B. J.、 SULPIZIO A. C.、 HIEBLE J. P.、 +

  DOI：——

  日期：——
• US4707485A
  申请人：——

  公开号：US4707485A

  公开（公告）日：1987-11-17