6,7-dimethoxy-1-styryl-3,4-dihydroisoquinoline | 5666-95-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢异喹啉
• 英文名称: 6,7-dimethoxy-1-styryl-3,4-dihydroisoquinoline
• 英文别名: 6,7-dimethoxy-1-[(E)-2-phenylethenyl]-3,4-dihydroisoquinoline
• CAS: 5666-95-5
• 化学式: C₁₉H₁₉NO₂
• 分子量: 293.365
• InChiKey: KNCCEEFRZQYSNI-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  30.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6,7-dimethoxy-1-styryl-3,4-dihydroisoquinoline 在 sodium tetrahydroborate 、 甲酸 作用下， 以 甲醇 为溶剂， 反应 4.0h， 生成 (E)-6,7-dimethoxy-2-methyl-1-styryl-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Dopaminergic isoquinolines with hexahydrocyclopenta[ ij ]-isoquinolines as D 2 -like selective ligands

  摘要：

  Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D-1 and D-2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the beta-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We observed that the most active compounds in the three series (2c, 2e, 3a, 3c, 3e, 5c and 5e) possessed a high affinity for D-2-like DR and these remarkable features: a catechol group in the IQ-ring and the N-substitution (methyl or allyl). The series showed the following trend to D-2-RD affinity: HCPIQs > 1-styryl > 1-propenyl. Therefore, the substituent at the beta-position of the THIQ and the cyclopentane ring also modulated this affinity. Among these dopaminergic isoquinolines, HCPIQs stood out for unexpected selectivity to D-2-DR since the Ki D-1/D-2 ratio reached values of 2465, 1010 and 382 for compounds 3a, 3c and 3e, respectively. None of the most active THIQs in D-2 DR displayed relevant cytotoxicity in human neutrophils and HUVEC. Finally, and in agreement with the experimental data, molecular modeling studies on DRs of the most characteristic ligands of the three series revealed stronger molecular interactions with D-2 DR than with D-1 DR, which further supports to the encountered enhanced selectivity to D-2 DR. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.06.009
• 作为产物：
  描述：

  N-(3,4-dimethoxyphenethyl)cinnamamide 在 三氯氧磷 作用下， 以 乙腈 为溶剂， 反应 5.0h， 生成 6,7-dimethoxy-1-styryl-3,4-dihydroisoquinoline
  参考文献：
  名称：

  Dopaminergic isoquinolines with hexahydrocyclopenta[ ij ]-isoquinolines as D 2 -like selective ligands

  摘要：

  Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D-1 and D-2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the beta-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We observed that the most active compounds in the three series (2c, 2e, 3a, 3c, 3e, 5c and 5e) possessed a high affinity for D-2-like DR and these remarkable features: a catechol group in the IQ-ring and the N-substitution (methyl or allyl). The series showed the following trend to D-2-RD affinity: HCPIQs > 1-styryl > 1-propenyl. Therefore, the substituent at the beta-position of the THIQ and the cyclopentane ring also modulated this affinity. Among these dopaminergic isoquinolines, HCPIQs stood out for unexpected selectivity to D-2-DR since the Ki D-1/D-2 ratio reached values of 2465, 1010 and 382 for compounds 3a, 3c and 3e, respectively. None of the most active THIQs in D-2 DR displayed relevant cytotoxicity in human neutrophils and HUVEC. Finally, and in agreement with the experimental data, molecular modeling studies on DRs of the most characteristic ligands of the three series revealed stronger molecular interactions with D-2 DR than with D-1 DR, which further supports to the encountered enhanced selectivity to D-2 DR. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.06.009

文献信息

• Tomimatsu, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1957, vol. 77, p. 7,10
  作者：Tomimatsu

  DOI：——

  日期：——
• Synthesis of hexahydrocyclopenta[ij]isoquinolines as a new class of dopaminergic agents
  作者：Javier Párraga、Abraham Galán、Maria Jesús Sanz、Nuria Cabedo、Diego Cortes

  DOI：10.1016/j.ejmech.2014.11.009

  日期：2015.1

  In this study, we have described the synthesis of the tricyclic 1,2,3,7,8,8a-hexahydrocyclopenta[ij]isoquinoline (HCPIQ). Herein, six differently substituted 5,6-dioxygenated-7-phenyl-HCPIQs have been synthesized using a new methodology via (E)-1-styryl-THIQ by Friedel Crafts cyclization with Eaton's reagent. Results showed that HCPIQs (3, 3a-e) displayed a moderate affinity for D-1 dopamine receptors (DR) in the micromolar range, furthermore the catecholic HCPIQs 3a (NH), 3c (NCH3) and 3e (NCH2CH=CH2) exhibited outstanding affinity and high selectivity towards D-2 DR. Indeed, 3a, 3c and 3e showed Ki values of 29 nM, 13 nM and 18 nM, respectively, and HCPIQs 3a (NH) and 3c (NCH3) displayed a remarkable selectivity (Ki D-1/D-2 ratio similar to 1000-2500). In addition, none of the catecholic compounds showed any cytotoxicity in freshly isolated human neutrophils. Although further studies are needed, these compounds and particularly catecholic HCPIQs, show high potential in the treatment of Parkinson's disease, psychosis or depression. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Dopaminergic isoquinolines with hexahydrocyclopenta[ ij ]-isoquinolines as D 2 -like selective ligands
  作者：Javier Párraga、Sebastián A. Andujar、Sebastián Rojas、Lucas J. Gutierrez、Noureddine El Aouad、M. Jesús Sanz、Ricardo D. Enriz、Nuria Cabedo、Diego Cortes

  DOI：10.1016/j.ejmech.2016.06.009

  日期：2016.10

  Dopamine receptors (DR) ligands are potential drug candidates for treating neurological disorders including schizophrenia or Parkinson's disease. Three series of isoquinolines: (E)-1-styryl-1,2,3,4-tetrahydroisoquinolines (series 1), 7-phenyl-1,2,3,7,8,8a-hexahydrocyclopenta[ij]-IQs (HCPIQs) (series 2) and (E)-1-(prop-1-en-1-yl)-1,2,3,4- tetrahydroisoquinolines (series 3), were prepared to determine their affinity for both D-1 and D-2-like DR. The effect of different substituents on the nitrogen atom (methyl or allyl), the dioxygenated function (methoxyl or catechol), the substituent at the beta-position of the THIQ skeleton, and the presence or absence of the cyclopentane motif, were studied. We observed that the most active compounds in the three series (2c, 2e, 3a, 3c, 3e, 5c and 5e) possessed a high affinity for D-2-like DR and these remarkable features: a catechol group in the IQ-ring and the N-substitution (methyl or allyl). The series showed the following trend to D-2-RD affinity: HCPIQs > 1-styryl > 1-propenyl. Therefore, the substituent at the beta-position of the THIQ and the cyclopentane ring also modulated this affinity. Among these dopaminergic isoquinolines, HCPIQs stood out for unexpected selectivity to D-2-DR since the Ki D-1/D-2 ratio reached values of 2465, 1010 and 382 for compounds 3a, 3c and 3e, respectively. None of the most active THIQs in D-2 DR displayed relevant cytotoxicity in human neutrophils and HUVEC. Finally, and in agreement with the experimental data, molecular modeling studies on DRs of the most characteristic ligands of the three series revealed stronger molecular interactions with D-2 DR than with D-1 DR, which further supports to the encountered enhanced selectivity to D-2 DR. (C) 2016 Elsevier Masson SAS. All rights reserved.