2-benzoyl-6,7-dichloro-1-cyano-1,2-dihydroisoquinoline | 103959-61-1

• 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
• 英文名称: 2-benzoyl-6,7-dichloro-1-cyano-1,2-dihydroisoquinoline
• 英文别名: 2-benzoyl-6,7-dichloro-1H-isoquinoline-1-carbonitrile
• CAS: 103959-61-1
• 化学式: C₁₇H₁₀Cl₂N₂O
• 分子量: 329.185
• InChiKey: VRQDNSZUYCUWIB-UHFFFAOYSA-N

物化性质

• 熔点：
  104-106 °C
• 沸点：
  556.1±50.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-benzoyl-6,7-dichloro-1-cyano-1,2-dihydroisoquinoline 在 盐酸 、 sodium hydroxide 、 三氟化硼 、 苄基三乙基氯化铵 作用下， 以 甲苯 为溶剂， 反应 11.5h， 生成 6,7-dichloro-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline
  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 palladium on activated charcoal 、 18-冠醚-6 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 19.5h， 生成 2-benzoyl-6,7-dichloro-1-cyano-1,2-dihydroisoquinoline
  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。
• Cellular mechanisms of inhibition of superoxide anion generation in rat neutrophils by the synthetic isoquinoline DMDI
  作者：Jih-Pyang Wang、Ling-Chu Chang、Shue-Ling Raung、Mei-Feng Hsu、Chi-Ming Chen

  DOI：10.1016/s0014-2999(01)01536-9

  日期：2002.1

  This study was undertaken to assess the cellular localization of the inhibitory effect of a chemically synthetic isoquinoline compound 1-(3', 4'-dimethoxybenzyl)-6,7-dichloroisoquinoline (DMDI) on the formyl-methionyl-leucyl-phenylalanine (fMLP)-induced respiratory burst in rat neutrophils. The DMDI concentration dependently inhibited the superoxide anion (0;) generation and 02 Consumption (IC50 12.2 +/- 4.9 and 15.2 +/- 8.4 muM, respectively) of neutrophils. DMDI did not scavenge the O-2(.-) generated during the autoxidation of dihydroxyfumaric acid in a cell-free system. DMDI did not elevate cellular cyclic AMP levels. Inhibition of O-2(.-) generation by DMDI in neutrophils was not reversed by a cyclic AMP-dependent protein kinase inhibitor, (8R,9S,11S)-(-)-9-hydroxy-9-hexoxycarbonyl-8-methyl-2,3,9, 10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b, 11a-triazadibenzo[a,g]cycloocta[cde]trinden-1-one (KT5720). The DMDI concentration dependently inhibited the late plateau phase but not the initial spike of fMLP-induced [Ca2+](i) changes in the presence of extracellular Ca2+. However, DMDI had no effect on the fMLP-induced [Ca2+](i) changes in the absence of extracellular Ca2+. In addition, DMDI did not affect the fMLP-stimulated phosphatidylinositol 3-kinase (PI3-kinase) activation. DMDI produced a concentration-dependent reduction in the formation of phosphatidic acid and phosphatidylethanol in the presence of ethanol from fMLP-stimulated neutrophils (IC50 13.3 +/- 4.0 and 9.4 +/- 4.3 muM, respectively). On the basis of the immunoblot analysis of the phosphorylation of the mitogen-activated protein (MAP) kinase, DMDI attenuated the fMLP-stimulated MAP kinase phosphorylation in a similar concentration range. Collectively, these results indicate that the inhibition of the respiratory burst by DMDI in rat neutrophils is mediated through the blockade of phospholipase D and MAP kinase signaling pathways. (C) 2002 Elsevier Science B.V. All rights reserved.
• 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：——