1-(3-thienyl)-3,4-dihydroisoquinoline | 126138-87-2

• 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: 1-(3-thienyl)-3,4-dihydroisoquinoline
• 英文别名: 3,4-dihydro-1-(3-thienyl)isoquinoline；1-thiophen-3-yl-3,4-dihydroisoquinoline
• CAS: 126138-87-2
• 化学式: C₁₃H₁₁NS
• 分子量: 213.303
• InChiKey: HBALWXLTPDKZCF-UHFFFAOYSA-N

物化性质

• 沸点：
  160 °C(Press: 0.08 Torr)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(3-thienyl)-3,4-dihydroisoquinoline 在 sodium tetrahydroborate 作用下， 以 氘代甲醇-d 、 丙酮 为溶剂， 生成 4,7,8,12b-tetrahydro-5H-thieno[3',2':3,4]pyrido[2,1-a]isoquinoline
  参考文献：
  名称：

  D 1-样受体，可区分硫杂a​​嗪区域异构体

  摘要：

  由于受体螺旋内的高度同一性，设计具有D 1 / D 5亚型选择性的配体是一项挑战。基于先导化合物1-3，合成了噻吩-苯并ze庚因区域异构体4和5，并使用放射性配体结合亲和力技术对它们对五种多巴胺受体亚型的亲和力进行了生物学评估。内的d 1样家族，化合物4显示出对d 20倍的选择性5亚型超过d 1亚型（ķ我= 3nm时，d 1：60纳米），而它的区域异构体，化合物5用颠倒噻吩位置，更喜欢d 1在d亚型5亚型（ķ我= 4nM的，d 5：15纳米）。苯并噻吩并-苯并ze庚因类似物6被证明是对D 1-和D 2-样家族成员具有相同亲和力的几个数量级（A D 2和1.9的K i = 1.5 nM）具有高亲和力的a嗪衍生物之一。D 5为nM ）。彻底分析构成目标多巴胺受体亚型结合口袋的氨基酸残基，发现在D 5 通过阴离子氨基酸稳定的丝氨酸S 6.62和苏氨酸T 7.33残基或水网络的受体可能有助于合成化合物的选择性模式。

  DOI：

  10.1039/c5md00258c
• 作为产物：
  描述：

  3-噻吩甲酰氯 在 phosphorus pentoxide 、 三氯氧磷 作用下， 以 甲苯 为溶剂， 生成 1-(3-thienyl)-3,4-dihydroisoquinoline
  参考文献：
  名称：

  脑保护剂的研究。X.新型4,5,6,7-四氢噻吩并[3,3-c]吡啶和相关化合物的抗惊厥活性的合成和评价。

  摘要：

  新型4,5,6,7-四氢噻吩并[3,2-c]吡啶，1-噻吩基-1,2,3,4-四氢异喹啉和相关化合物，其中（+）-1的苯环（FR115427）用杂芳环如噻吩，呋喃，苯并噻吩和吲哚取代，合成并评估其对小鼠ICV N-甲基-D-天冬氨酸（NMDA）诱导的癫痫的抗惊厥活性。在这些化合物中，（+）-4-甲基-4-苯基-4,5,6,7-四氢噻吩并[3,2-c]吡啶盐酸盐（（+）-2a），（+）-4-甲基- 4-（2-噻吩基）-4,5,6,7-四氢噻吩并[3,2-c]吡啶盐酸盐（（+）-2g）和（-）1-甲基-2-（2-噻吩基）- 1,2,3,4-四氢异喹啉盐酸盐（（-）-3a）显示出显着的抗惊厥活性。讨论了与该系列化合物的抗惊厥活性有关的构效关系。

  DOI：

  10.1248/cpb.44.778

文献信息

• Dopamine/Serotonin Receptor Ligands. 10: SAR Studies on Azecine-type Dopamine Receptor Ligands by Functional Screening at Human Cloned D₁, D_2L, and D₅ Receptors with a Microplate Reader Based Calcium Assay Lead to a Novel Potent D₁/D₅ Selective Antagonist
  作者：Barbara Hoefgen、Michael Decker、Patrick Mohr、Astrid M. Schramm、Sherif A. F. Rostom、Hussein El-Subbagh、Peter M. Schweikert、Dirk R. Rudolf、Matthias U. Kassack、Jochen Lehmann

  DOI：10.1021/jm050846j

  日期：2006.1.1

  On the basis of the benz[d]indolo[2,3-g]azecine derivative I (LE300), structure-activity relations were investigated in order to identify the pharmacophore in this new class of ligands. Various structural modifications were performed and the inhibitory activities at human cloned D-1, D-2L, and D-5 receptors were measured by using a simple fluorescence microplate reader based calcium assay. Subsequently, the affinities of active compounds were estimated by radioligand binding experiments. Deleting one of the aromatic rings as well as replacing it by a phenyl moiety abolishes the inhibitory activities almost completely. Contraction of the 10-membered central ring decreases them significantly. The replacement of indole by thiophene or N-methylpyrrole reduces the inhibitory activity, whereas replacing the indole by benzene increases it. Finally, the hydroxylated dibenz[d,g]azecine derivative 11d (LE404) was found to be more active than the lead I in the functional calcium assay as well as in radioligand displacement experiments.
• Synthesis and Antimuscarinic Properties of Quinuclidin-3-yl 1,2,3,4-Tetrahydroisoquinoline-2-carboxylate Derivatives as Novel Muscarinic Receptor Antagonists
  作者：Ryo Naito、Yasuhiro Yonetoku、Yoshinori Okamoto、Akira Toyoshima、Ken Ikeda、Makoto Takeuchi

  DOI：10.1021/jm050099q

  日期：2005.10.1

  In the course of continuing efforts to develop potent and bladder-selective muscarinic M-3 receptor antagonists, quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives and related compounds were designed as conformationally restricted analogues of quinuclidin-3-yl benzhydrylcarbamate (8). Binding assays with rat muscarinic receptor subtypes revealed that the quinuclidin-3-yl 1-aryl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate derivatives showed high affinities for the M3 receptor, and selectivity for the M3 receptor over the M-2 receptor. Of these derivatives, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monohydrochloride (9b) exhibited almost the same inhibitory activity against bladder contraction to that of oxybutynin (1), and more than 10-fold selectivity for bladder contraction versus salivary secretion, demonstrating that 9b may be useful for the treatment of symptoms associated with overactive bladder without having side effects such as dry mouth.
• Tetrahydroisoquinolines and tetrahydrobenzazepines and a process for the preparation thereof
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0336228B1

  公开（公告）日：1994-11-09
• US5059608A
  申请人：——

  公开号：US5059608A

  公开（公告）日：1991-10-22
• D₁-like receptors distinguishing thieno-azecine regioisomers
  作者：Mohamed A. O. Abdel-Fattah、Ashraf H. Abadi、Jochen Lehmann、Peter M. Schweikert、Christoph Enzensperger

  DOI：10.1039/c5md00258c

  日期：——

  subtype selectivity is a challenge because of the high identity within the receptor helices. Based on the lead compounds 1–3, the thieno-benzazecine regioisomers 4 and 5 were synthesized and biologically evaluated for their affinity towards the five dopamine receptor subtypes utilizing a radioligand binding affinity technique. Within the D1-like family, compound 4 showed 20 fold selectivity for the

  由于受体螺旋内的高度同一性，设计具有D 1 / D 5亚型选择性的配体是一项挑战。基于先导化合物1-3，合成了噻吩-苯并ze庚因区域异构体4和5，并使用放射性配体结合亲和力技术对它们对五种多巴胺受体亚型的亲和力进行了生物学评估。内的d 1样家族，化合物4显示出对d 20倍的选择性5亚型超过d 1亚型（ķ我= 3nm时，d 1：60纳米），而它的区域异构体，化合物5用颠倒噻吩位置，更喜欢d 1在d亚型5亚型（ķ我= 4nM的，d 5：15纳米）。苯并噻吩并-苯并ze庚因类似物6被证明是对D 1-和D 2-样家族成员具有相同亲和力的几个数量级（A D 2和1.9的K i = 1.5 nM）具有高亲和力的a嗪衍生物之一。D 5为nM ）。彻底分析构成目标多巴胺受体亚型结合口袋的氨基酸残基，发现在D 5 通过阴离子氨基酸稳定的丝氨酸S 6.62和苏氨酸T 7.33残基或水网络的受体可能有助于合成化合物的选择性模式。