3-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)propionitrile | 92595-50-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 3-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)propionitrile
• 英文别名: 3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)propanenitrile；2-(2-cyanoethyl)-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline；3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)propanenitrile
• CAS: 92595-50-1
• 化学式: C₁₄H₁₈N₂O₂
• mdl: MFCD00439349
• 分子量: 246.309
• InChiKey: XZLIRBUUBBTGRP-UHFFFAOYSA-N

物化性质

• 沸点：
  410.7±45.0 °C(Predicted)
• 密度：
  1.105±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)propionitrile 在 sodium hydroxide 、 Dowex 1X₈ chloride resin 、 氢气 、 镍 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 60.0h， 生成
  参考文献：
  名称：

  In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450

  摘要：

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency of the P-glycoprotein (P-gp) transporter. The aromatic spacer group between nitrogen atoms (N1 and N2) in the known inhibitor XR9576 was replaced with a flexible alkyl chain of 2 to 6 carbon atoms in length. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline and their open-chain N-methylhomoveratrylamine counterparts were shown to be potent P-gp inhibitors. The maximal inhibition was obtained when using an ethyl or propyl spacer. Several compounds were more potent than verapamil and intrinsically less cytotoxic than XR9576. In addition, in vitro metabolism studies of 23a with a subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs such as paclitaxel toward metabolism. In this context, 22a might be a suitable candidate for further drug development.

  DOI：

  10.1016/j.bmc.2006.07.055
• 作为产物：
  描述：

  β-氯丙腈 、 6,7-二甲氧基-1,2,3,4-四氢异喹啉 在 sodium carbonate 、 sodium iodide 作用下， 以 叔丁醇 为溶剂， 反应 24.0h， 以29%的产率得到3-(6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)propionitrile
  参考文献：
  名称：

  In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity at CYP-450

  摘要：

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency of the P-glycoprotein (P-gp) transporter. The aromatic spacer group between nitrogen atoms (N1 and N2) in the known inhibitor XR9576 was replaced with a flexible alkyl chain of 2 to 6 carbon atoms in length. 6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline and their open-chain N-methylhomoveratrylamine counterparts were shown to be potent P-gp inhibitors. The maximal inhibition was obtained when using an ethyl or propyl spacer. Several compounds were more potent than verapamil and intrinsically less cytotoxic than XR9576. In addition, in vitro metabolism studies of 23a with a subset of human CYP-450 isoforms revealed that, unlike XR9576, 23a inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of anticancer drugs such as paclitaxel toward metabolism. In this context, 22a might be a suitable candidate for further drug development.

  DOI：

  10.1016/j.bmc.2006.07.055

文献信息

• Dihydropyridines and new uses thereof
  申请人：Synaptic Pharmaceutical Corporation

  公开号：US05767131A1

  公开（公告）日：1998-06-16

  The invention provides a method of treating benign prostatic hyperplasia in a subject which comprises administering to the subject a therapeutically effective amount of a compound having the structure: ##STR1## wherein Y is --(CH.sub.2).sub.n --, where n is 1, 2, 3, 4 or 5; --(CH.sub.2).sub.h --O--(CH.sub.2).sub.k --, where h and k are independently the same or different and are 2, 3 or 4; --(CH.sub.2).sub.h --CH.dbd.CH--(CH.sub.2).sub.k --; or --(CH.sub.2).sub.h --C.tbd.C--(CH.sub.2).sub.k --, where h and k are independently the same or different and are 1, 2, 3 or 4; wherein Z is O, NH, or CH.sub.2 ; wherein R.sup.1 is a linear or branched chain alkyl, alkoxyalkyl or arylalkyl group; wherein R.sup.2 and R.sup.4 are independently the same or different and are H, or a linear or branched chain alkyl group; wherein R.sup.3 is H, a linear or branched chain alkyl, alkoxy, alkoxyalkyl or acyl group; and wherein R.sup.5 and R.sup.6 are independently the same or different and are H, OH, Cl, Br, F, NO.sub.2, CN, CF.sub.3, or NH.sub.2, or a linear or branched chain alkyl, alkoxy, alkoxycarbonyl, acyl, alkylsulfoxide, alkylsulfone, or mono- or dialkylamino group. Other active compounds containing one, two or three rings are also disclosed as well as pharmaceutical compositions prepared therefrom and methods of use in the treatment of BPH, inhibition of cholesterol synthesis, and reduction of intraocular pressure.

  该发明提供了一种治疗良性前列腺增生的方法，包括向受试者施用具有以下结构的化合物的治疗有效量： 其中Y为--(CH.sub.2).sub.n --，其中n为1、2、3、4或5；--(CH.sub.2).sub.h --O--(CH.sub.2).sub.k --，其中h和k独立且相同或不同，为2、3或4；--(CH.sub.2).sub.h --CH.dbd.CH--(CH.sub.2).sub.k --；或--(CH.sub.2).sub.h --C.tbd.C--(CH.sub.2).sub.k --，其中h和k独立且相同或不同，为1、2、3或4；其中Z为O、NH或CH.sub.2；其中R.sup.1为线性或支链烷基、烷氧基烷基或芳基烷基；其中R.sup.2和R.sup.4独立且相同或不同，为H，或线性或支链烷基；其中R.sup.3为H、线性或支链烷基、烷氧基、烷氧基烷基或酰基；其中R.sup.5和R.sup.6独立且相同或不同，为H、OH、Cl、Br、F、NO.sub.2、CN、CF.sub.3或NH.sub.2，或线性或支链烷基、烷氧基、烷氧羰基、酰基、烷基亚砜、烷基砜、或单烷基或二烷基氨基基团。还公开了含有一、两个或三个环的其他活性化合物，以及由此制备的药物组合物和在治疗BPH、抑制胆固醇合成和降低眼压中的使用方法。
• ^99mTc-Cyclopentadienyl Tricarbonyl Chelate-Labeled Compounds as Selective Sigma-2 Receptor Ligands for Tumor Imaging
  作者：Dan Li、Yuanyuan Chen、Xia Wang、Winnie Deuther-Conrad、Xin Chen、Bing Jia、Chengyan Dong、Jörg Steinbach、Peter Brust、Boli Liu、Hongmei Jia

  DOI：10.1021/acs.jmedchem.5b01378

  日期：2016.2.11

  receptor affinity (Ki = 2.97 nM) and moderate subtype selectivity (10-fold). Moreover, it showed high selectivity toward vesicular acetylcholine transporter (2374-fold), dopamine D2L receptor, NMDA receptor, opiate receptor, dopamine transporter, norepinephrine transporter, and serotonin transporter. Its corresponding radiotracer [99mTc]20b showed high uptake in a time- and dose-dependent manner in DU145

  我们设计并合成了含有5,6- dimethoxyisoindoline或6,7-二甲氧基-1,2,3,4-四氢异喹啉作为药效σ一系列环戊二烯基三羰基铼配合2受体配体。铼化合物20A具有低纳摩尔σ 2受体的亲和力（ķ我= 2.97 nM）的和中度的亚型选择性（10倍）。此外，它对水泡乙酰胆碱转运蛋白（2374倍），多巴胺D 2L受体，NMDA受体，阿片受体，多巴胺转运蛋白，去甲肾上腺素转运蛋白和5-羟色胺转运蛋白显示出很高的选择性。其相应的放射性示踪剂[ 99m Tc] 20b在DU145前列腺细胞和C6胶质瘤细胞中显示出高吸收，呈时间和剂量依赖性。此外，该示踪剂在裸鼠中显示出高的肿瘤吸收率（在240分钟时为5.92％ID / g）和高的肿瘤/血液和肿瘤/肌肉比率（在240分钟时分别为21和16）以及与σ受体的特异性结合带有C6胶质瘤异种移植物。C6胶质瘤异种移植模型中[ 99m Tc] 20b的小动物SPECT
• Addition of isoquinolines to activated C=C double bonds, and the biological properties of the products
  作者：G. K. Airapetyan、R. É. Markaryan、É. M. Arzanunts、I. S. Sarkisyan、R. R. Safrazbekyan、É. A. Markaryan

  DOI：10.1007/bf00776793

  日期：1984.6

  Makurina, Reakts. Sposobnost' Organ. Soedin., Vol. 9, No. I, 157-162 (1972). 7. A. S. Saratikov and N. P. Skakun, Cholagenic and Cholagogic Drugs [in Russian], Tomsk (1972), pp. 138-170. 8. N. P. Skakun, Probl. Endokrinol., No. 6, 75-80 (1956). J 9. E. Shtern and K. Timmons, Electronic Absorption Spectroscopy in Organic Chemistry [in Russian], Moscow (1974), pp. 157-161. i0. P. Meyer and Sundmacher, Ber.

  我呀。Belen'kii Fundamentals of the Quantitative Measurement of Pharmacological Activity (2nd edn.) [in Russian], Leningrad (1963), p. 81. 2. SM Drogovoz，利胆药物作用的比较研究和特征 [俄文，作者的绝对，博士。Diss., Khar'kov (1972)。3. KI Karbich, Biokhimiya, No. 2, 305-309 (1961)。4. PA Petyunin 和 MV Zakalyuzhnyi, Zh。奥布希。Khim., No. i, 28-32 (1964)。5. PA Petyunin 和副总裁 Chernykh，gh。组织。Khim., No. 2, 285-286 (1965)。6. PA Petyunin，副总裁
• Arylamides hybrids of two high-affinity σ2 receptor ligands as tools for the development of PET radiotracers
  作者：Carmen Abate、Savina Ferorelli、Marialessandra Contino、Roberta Marottoli、Nicola Antonio Colabufo、Roberto Perrone、Francesco Berardi

  DOI：10.1016/j.ejmech.2011.05.057

  日期：2011.9

  1-Cyclohexy1-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) and 2-Methoxy-5-methyl-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)butyl]benzamide 2 (RHM-1) represent leads for tumor diagnosis, given their high affinity at sigma(2) receptors. With the purpose of obtaining good candidates for sigma(2) PET tracers development, hybrid structures between 1 and 2 were designed. Excellent sigma(1)/sigma(2) selectivities were reached when 6,7-dimethoxytetrahydroisoquinoline was linked to an o-methoxy substituted arylamide (11a, 12a, 15a). and for these benzamides an intramolecular H-bond in the active conformation at the sigma sites, was hypothesized. However these excellent sigma(2) ligands were accompanied by interaction with P-gp. which may limit their use as sigma(2) receptor PET agents when tumors overexpress P-gp. Compound 15a whose P-gp interaction was just moderate represents an interesting tool for the development of sigma(2) PET tracers useful in tumors overexpressing P-gp. (C) 2011 Elsevier Masson SAS. All rights reserved.
• AJRAPETYAN, G. K.;MARKARYAN, R. EH.;ARZANUNTS, EH. M.;SARKISYAN, I. S.;SA+, XIM.-FARMATS. ZH., 1984, 18, N 6, 686-689
  作者：AJRAPETYAN, G. K.、MARKARYAN, R. EH.、ARZANUNTS, EH. M.、SARKISYAN, I. S.、SA+

  DOI：——

  日期：——