2,2,2-trifluoro-1-(6-methoxy-3,4-dihydroisoquinolin- 2(1H)-yl)ethanone | 1281902-33-7

• 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: 2,2,2-trifluoro-1-(6-methoxy-3,4-dihydroisoquinolin- 2(1H)-yl)ethanone
• 英文别名: 2,2,2-Trifluoro-1-(6-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethanone；2,2,2-trifluoro-1-(6-methoxy-3,4-dihydro-1H-isoquinolin-2-yl)ethanone
• CAS: 1281902-33-7
• 化学式: C₁₂H₁₂F₃NO₂
• 分子量: 259.228
• InChiKey: XZXDYUZQONETNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,2,2-trifluoro-1-(6-methoxy-3,4-dihydroisoquinolin- 2(1H)-yl)ethanone 在 盐酸 、 palladium 10% on activated carbon 、 氢气 、 硝酸 作用下， 以 甲醇 、 乙二醇乙醚 、 三氟乙酸 为溶剂， 反应 27.0h， 生成 1-(7-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)-6-methoxy-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethan-1-one
  参考文献：
  名称：

  Discovery of novel tetrahydroisoquinoline-containing pyrimidines as ALK inhibitors

  摘要：

  Exploration of the two-position side chain of pyrimidine in LDK378 with tetrahydroisoquinolines (THIQs) led to discovery of 8 and 17 as highly potent ALK inhibitors. THIQs 8 and 17 showed encouraging in vitro and in vivo xenograft efficacies, comparable with those of LDK378. Although THIQ analogs (8a-o and 17a-i) prepared were not as active as their parent compounds, both 8 and 17 have significant inhibitory activities against various ALK mutant enzymes including G1202R, indicating that this series of compounds could be further optimized as useful ALK inhibitors overcoming the resistance issues found from crizotinib and LDK378. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.004
• 作为产物：
  描述：

  methyl 3-methoxyphenethylcarbamate 在 lithium aluminium tetrahydride 、 三乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 21.0h， 生成 2,2,2-trifluoro-1-(6-methoxy-3,4-dihydroisoquinolin- 2(1H)-yl)ethanone
  参考文献：
  名称：

  Discovery of novel tetrahydroisoquinoline-containing pyrimidines as ALK inhibitors

  摘要：

  Exploration of the two-position side chain of pyrimidine in LDK378 with tetrahydroisoquinolines (THIQs) led to discovery of 8 and 17 as highly potent ALK inhibitors. THIQs 8 and 17 showed encouraging in vitro and in vivo xenograft efficacies, comparable with those of LDK378. Although THIQ analogs (8a-o and 17a-i) prepared were not as active as their parent compounds, both 8 and 17 have significant inhibitory activities against various ALK mutant enzymes including G1202R, indicating that this series of compounds could be further optimized as useful ALK inhibitors overcoming the resistance issues found from crizotinib and LDK378. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.12.004

文献信息

• Compounds
  申请人：Forbes Thomson Ian

  公开号：US20050261279A1

  公开（公告）日：2005-11-24

  The invention provides compounds of formula (I): wherein A and B represent the groups —(CH 2 ) m — and —(CH 2 ) n — respectively; R 1 represents hydrogen or C 1-6 alkyl; R 2 represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxy C 1-6 alkyl, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 fluoroalkoxy, —(CH 2 ) p C 3-6 cycloalkyl, —(CH 2 ) p OC 3-6 cycloalkyl, —COC 1-6 alkyl, —SO 2 C 1-6 alkyl, —SOC 1-6 alkyl, —S—C 1-6 alkyl, —CO 2 C 1-6 alkyl, —CO 2 NR 5 R 6 , —SO 2 NR 5 R 6 , —(CH 2 ) p NR 5 R 6 , —(CF) p NR 5 COR 6 , optionally substituted aryl ring, optionally substituted heteroaryl ring or optionally substituted heterocyclyl ring; R 3 represents optionally substituted aryl ring or optionally substituted heteroaryl ring; R 4 represents hydrogen, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, trifluoromethyl, trifluoromethoxy, halogen, —OSO 2 CF 3 , —(CH 2 ) p C 3-6 cycloalkyl, —(CH 2 ) q OC 1-6 alkyl or —(CH 2 ) p OC 3-6 cycloalkyl; R 5 and R 6 each independently represent hydrogen, C 1-6 alkyl or, together with the nitrogen or other atoms to which they are attached, form an azacycloalkyl ring or an oxo-substituted azacycloalkyl ring; Z represents —(CH 2 ) r X— wherein the —(CH 2 ) r — group is attached to R 3 , or —X(CH 2 ) r — wherein X is attached to R 3 , and wherein any of the —CH 2 — groups may be optionally substituted by one or more C 1-6 alkyl groups; X represents oxygen, —NR 7 or —CH 2 — wherein the —CH 2 — group may be optionally substituted by one or more C 1-6 alkyl groups; R 7 represents hydrogen or C 1-6 alkyl; m and n independently represent an integer selected from 1 and 2; p independently represents an integer selected from 0, 1, 2 and 3; q independently represents an integer selected from 1, 2 and 3; r independently represents an integer selected from 0, 1, and 2; or a pharmaceutically acceptable salt or solvate thereof. The compounds are useful in therapy, in particular as antipsychotic agents.

  本发明提供了式（I）的化合物： 其中，A和B分别代表基团—（CH2）m—和—（CH2）n—；R1代表氢或C1-6烷基；R2代表氢、卤素、羟基、氰基、硝基、羟基C1-6烷基、三氟甲基、三氟甲氧基、C1-6烷基、C1-6烷氧基、C1-6氟烷氧基、—（CH2）pC3-6环烷基、—（CH2）pOC3-6环烷基、—COC1-6烷基、—SO2C1-6烷基、—SOC1-6烷基、—S—C1-6烷基、—CO2C1-6烷基、—CO2NR5R6、—SO2NR5R6、—（CH2）pNR5R6、—（CF）pNR5COR6、可选地取代的芳环、可选地取代的杂芳环或可选地取代的杂环基；R3代表可选地取代的芳环或可选地取代的杂芳环；R4代表氢、羟基、C1-6烷基、C1-6烷氧基、三氟甲基、三氟甲氧基、卤素、—OSO2CF3、—（CH2）pC3-6环烷基、—（CH2）qOC1-6烷基或—（CH2）pOC3-6环烷基；R5和R6各自独立地代表氢、C1-6烷基或与它们所连接的氮或其他原子一起形成氮杂环烷基或氧代取代的氮杂环烷基；Z代表—（CH2）rX—，其中—（CH2）r—基团连接到R3，或—X（CH2）r—，其中X连接到R3，其中任何一个—CH2—基团可以可选地被一个或多个C1-6烷基基团取代；X代表氧、—NR7或—CH2—，其中—CH2—基团可以可选地被一个或多个C1-6烷基基团取代；R7代表氢或C1-6烷基；m和n独立地代表选自1和2的整数；p独立地代表选自0、1、2和3的整数；q独立地代表选自1、2和3的整数；r独立地代表选自0、1和2的整数；或其药学上可接受的盐或溶剂。这些化合物在治疗中有用，特别是作为抗精神病药物。
• AROMATIC SULFONES AND THEIR MEDICAL USE
  申请人：Forbes Ian Thomson

  公开号：US20080269197A1

  公开（公告）日：2008-10-30

  The invention provides compounds of formula (I): wherein A and B represent the groups —(CH 2 ) m — and —(CH 2 ) n — respectively; R 1 represents hydrogen or C 1-6 alkyl; R 2 represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxy C 1-6 alkyl, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 fluoroalkoxy, —(CH 2 ) p C 3-6 cycloalkyl, —(CH 2 ) p OC 3-6 cycloalkyl, —COC 1-6 alkyl, —SO 2 C 1-6 alkyl, —SOC 1-6 alkyl, —S—C 1-6 alkyl, —CO 2 C 1-6 alkyl, —CO 2 NR 5 R 6 , —SO 2 NR 5 R 6 , —(CH 2 ) p NR 5 R 6 , —(CH 2 ) p NR 5 COR 6 , optionally substituted aryl ring, optionally substituted heteroaryl ring or optionally substituted heterocyclyl ring; R 3 represents optionally substituted aryl ring or optionally substituted heteroaryl ring; R 4 represents hydrogen, hydroxy, C 1-6 alkyl, C 1-6 alkoxy, trifluoromethyl, trifluoromethoxy, halogen, —OSO 2 CF 3 , —(CH 2 ) p C 3-6 cycloalkyl, —(CH 2 ) q OC 1-6 alkyl or —(CH 2 ) p OC 3-6 cycloalkyl; R 5 and R 6 each independently represent hydrogen, C 1-6 alkyl or, together with the nitrogen or other atoms to which they are attached, form an azacycloalkyl ring or an oxo-substituted azacycloalkyl ring; Z represents —(CH 2 ) r X— wherein the —(CH 2 ) r — group is attached to R 3 , or —X(CH 2 ) r — wherein X is attached to R 3 , and wherein any of the —CH 2 — groups may be optionally substituted by one or more C 1-6 alkyl groups; X represents oxygen, —NR 7 or —CH 2 — wherein the —CH 2 — group may be optionally substituted by one or more C 1-6 alkyl groups; R 7 represents hydrogen or C 1-6 alkyl; m and n independently represent an integer selected from 1 and 2; p independently represents an integer selected from 0, 1, 2 and 3; q independently represents an integer selected from 1, 2 and 3; r independently represents an integer selected from 0, 1, and 2; or a pharmaceutically acceptable salt or solvate thereof. The compounds are useful in therapy, in particular as antipsychotic agents.

  本发明提供了式（I）的化合物：其中A和B分别代表基团-（CH2）m-和-（CH2）n-；R1代表氢或C1-6烷基；R2代表氢、卤素、羟基、氰基、硝基、羟基C1-6烷基、三氟甲基、三氟甲氧基、C1-6烷基、C1-6烷氧基、C1-6氟烷氧基、-（CH2）pC3-6环烷基、-（CH2）pOC3-6环烷基、-COC1-6烷基、-SO2C1-6烷基、-SOC1-6烷基、-S-C1-6烷基、-CO2C1-6烷基、-CO2NR5R6、-SO2NR5R6、-（CH2）pNR5R6、-（CH2）pNR5COR6、可选择取代的芳环、可选择取代的杂芳环或可选择取代的杂环烷基；R3代表可选择取代的芳环或可选择取代的杂芳环；R4代表氢、羟基、C1-6烷基、C1-6烷氧基、三氟甲基、三氟甲氧基、卤素、-OSO2CF3、-（CH2）pC3-6环烷基、-（CH2）qOC1-6烷基或-（CH2）pOC3-6环烷基；R5和R6各自独立地代表氢、C1-6烷基或与它们所附着的氮或其他原子一起形成一个氮杂环烷基或氧代取代的氮杂环烷基；Z代表-（CH2）rX-，其中-（CH2）r-基团附着在R3上，或-X（CH2）r-，其中X附着在R3上，并且任何-CH2-基团都可以选择地被一个或多个C1-6烷基取代；X代表氧、-NR7或-CH2-，其中-CH2-基团可以选择地被一个或多个C1-6烷基取代；R7代表氢或C1-6烷基；m和n分别独立地代表选自1和2的整数；p独立地代表选自0、1、2和3的整数；q独立地代表选自1、2和3的整数；r独立地代表选自0、1和2的整数；或其药学上可接受的盐或溶剂。这些化合物在治疗中有用，特别是作为抗精神病药物。
• 2,3,4,5-tetrahydro-1H-3-benzazepines and their medical use
  申请人：Glaxo Group Limited

  公开号：US07504392B2

  公开（公告）日：2009-03-17

  The invention provides compounds of the formula or a pharmaceutically acceptable salts thereof. The compounds are useful in therapy, in particular as antipsychotic agents.

  本发明提供式（I）化合物或其药学上可接受的盐。该化合物在治疗中有用，特别是作为抗精神病药物。
• [EN] AZEPINE FUSED RING COMPOUNDS AND MEDICAL USES THEREOF<br/>[FR] COMPOSÉS CYCLIQUES CONDENSÉS DU TYPE AZÉPINE ET UTILISATIONS MÉDICALES ASSOCIÉES<br/>[ZH] 氮杂卓类稠环化合物及其医药用途
  申请人：THE NAT INSTITUTES OF PHARMACEUTICAL R&D CO LTD

  公开号：WO2021228173A1

  公开（公告）日：2021-11-18

  本发明涉及氮杂卓类稠环化合物及其医药用途。具体地，本发明涉及通式(I)所示的氮杂卓类稠环化合物，其制备方法，含有其的药物组合物，以及其作为受体相互作用蛋白激酶1(RIP1)抑制剂，用于治疗与RIP1活性相关的疾病的用途。其中通式(I)中的各取代基的定义与说明书中的定义相同。
• Copper-Catalyzed <i>para</i>-Selective C–H Amination of Electron-Rich Arenes
  作者：Beatrise Berzina、Igors Sokolovs、Edgars Suna

  DOI：10.1021/acscatal.5b01992

  日期：2015.11.6

  A one-pot two-step method for para-selective C-H amination of carbocyclic arenes comprises the in situ formation of unsymmetrical diaryl-lambda(3)-iodanes followed by their Cu(I)-catalyzed reaction with a range of N-unprotected amines.