6-benzyloxy-1,2,3,4-tetrahydro-isoquinoline | 252061-94-2

• 物质功能分类: 医药中间体 - 杂环化合物 - 异喹啉类化合物
• 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: 6-benzyloxy-1,2,3,4-tetrahydro-isoquinoline
• 英文别名: 6-(Benzyloxy)-1,2,3,4-tetrahydroisoquinoline；6-phenylmethoxy-1,2,3,4-tetrahydroisoquinoline
• CAS: 252061-94-2
• 化学式: C₁₆H₁₇NO
• 分子量: 239.317
• InChiKey: NGIMVZRTBZCSPM-UHFFFAOYSA-N

物化性质

• 沸点：
  400.5±45.0 °C(Predicted)
• 密度：
  1.102±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  6-benzyloxy-1,2,3,4-tetrahydro-isoquinoline 在 palladium on activated charcoal 氢气 、 苄基三甲基氢氧化铵 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.0h， 生成 tert-butyl 2-[6-[[4-[N'-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]phenyl]methoxy]-3,4-dihydro-1H-isoquinolin-2-yl]acetate
  参考文献：
  名称：

  Fused Bicyclic Gly-Asp β-Turn Mimics with Specific Affinity for GPIIb-IIIa

  摘要：

  Disubstituted isoquinolones 2 and 3 have affinity for GPIIb-IIIa and represent leads for further structural evaluation. Structure-activity studies centered on the bicyclic beta-turn mimic contained in these molecules indicated that this moiety could accommodate a variety of modifications. Specifically, monocyclic, 6,5-bicyclic, and 6,7-bicyclic structures provide compounds with affinity for GPIIb-IIIa. Within the 6,6-series, isoquinoline, tetralin, tetralone, and benzopyran nuclei yield potent antagonists that are specific for GPIIb-IIIa. Attachment of the arginine isostere (benzamidine) to the supporting nucleus can be accomplished with an ether or amide linkage, although the latter enhances activity. Several compounds in this series provided measurable blood levels after oral dosing. Conversion of the acid moiety in these molecules to an ester generally provided compounds which gave greater systemic exposure after oral administration. Absolute bioavailabilities in the rat for the ethyl ester prodrug derivatives of the tetralin, tetralone, and benzopyran analogues of 3 were 28%, 23%, and 24%, respectively.

  DOI：

  10.1021/jm990365y
• 作为产物：
  描述：

  1,2,3,4-四氢异喹啉-6-醇 在 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 58.66h， 生成 6-benzyloxy-1,2,3,4-tetrahydro-isoquinoline
  参考文献：
  名称：

  Cu ^II /TEMPO‐Catalyzed Enantioselective C(sp ³ )–H Alkynylation of Tertiary Cyclic Amines through Shono‐Type Oxidation

  摘要：

  AbstractA novel strategy for asymmetric Shono‐type oxidative cross‐coupling has been developed by merging copper catalysis and electrochemistry, affording C1‐alkynylated tetrahydroisoquinolines with good to excellent enantioselectivity. The use of TEMPO as a co‐catalytic redox mediator is crucial not only for oxidizing a tetrahydroisoquinoline to an iminium ion species but also for decreasing the oxidation potential of the reaction. A novel bisoxazoline ligand is also reported.

  DOI：

  10.1002/anie.202005099

文献信息

• [EN] TETRAHYDROISOQUINOLINE ESTROGEN RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS DES RÉCEPTEURS D'ŒSTROGÈNES TÉTRAHYDROISOQUINOLÉINE ET LEURS UTILISATIONS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017174757A1

  公开（公告）日：2017-10-12

  Described herein are tetrahydroisoquinoline compounds with estrogen receptor modulation activity or function having the Formula I structure: I and stereoisomers, tautomers, or pharmaceutically acceptable salts thereof, and with the substituents and structural features described herein. Also described are pharmaceutical compositions and medicaments that include the Formula I compounds, as well as methods of using such estrogen receptor modulators, alone and in combination with other therapeutic agents, for treating diseases or conditions that are mediated or dependent upon estrogen receptors.

  本发明描述了具有雌激素受体调节活性的四氢异喹啉化合物或具有I式结构的功能：I及其立体异构体、互变异构体或药用可接受盐，以及本发明所描述的取代基和结构特征。还描述了包括I式化合物的药物组合物和药品，以及使用这样的雌激素受体调节剂的方法，单独使用或与其他治疗剂联合使用，用于治疗通过雌激素受体介导或依赖的疾病或状况。
• [EN] S1P RECEPTORS MODULATORS<br/>[FR] MODULATEURS DES RÉCEPTEURS S1P
  申请人：AKAAL PHARMA PTY LTD

  公开号：WO2010042998A1

  公开（公告）日：2010-04-22

  The invention relates to novel compounds that have S1P receptor modulating activity and, preferably, apoptotic activity and/or anti proliferative activity against cancer cells and other cell types. Further, the invention relates to a pharmaceutical comprising at least one compound of the invention for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression, for example, cancer. A further aspect of the invention relates to the use of a pharmaceutical comprising at least one compound of the invention for the manufacture of a medicament for the treatment of diseases and/or conditions caused by or associated with inappropriate S1P receptor modulating activity or expression such as cancer.

  该发明涉及具有S1P受体调节活性的新化合物，最好具有对癌细胞和其他细胞类型具有凋亡活性和/或抗增殖活性。此外，该发明涉及包含该发明中至少一种化合物的药物，用于治疗由不当的S1P受体调节活性或表达引起或相关的疾病和/或病况，例如癌症。该发明的另一个方面涉及使用包含该发明中至少一种化合物的药物制备药物，用于治疗由不当的S1P受体调节活性或表达引起或相关的疾病和/或病况，如癌症。
• Discovery of 5-Phenoxy-2-aminopyridine Derivatives as Potent and Selective Irreversible Inhibitors of Bruton’s Tyrosine Kinase
  作者：Eun Lee、Hyewon Cho、Da Kyung Lee、JuHyun Ha、Byeong Jo Choi、Ji Hye Jeong、Jae-Ha Ryu、Jong Soon Kang、Raok Jeon

  DOI：10.3390/ijms21218006

  日期：——

  due to its crucial roles in the B cell receptor (BCR) signaling pathway. Although many types of BTK inhibitors have been reported, there is an unmet need to achieve selective BTK inhibitors to reduce side effects. To obtain BTK selectivity and efficacy, we designed a novel series of type II BTK inhibitors which can occupy the allosteric pocket induced by the DFG-out conformation and introduced an electrophilic

  作为酪氨酸蛋白激酶Tec（TEC）家族的成员，布鲁顿的酪氨酸激酶（BTK）由于其在B细胞受体（BCR）信号传导途径中的关键作用而被认为是有前途的治疗靶标。尽管已经报道了许多类型的BTK抑制剂，但仍存在未达到实现选择性BTK抑制剂以减少副作用的需求。为了获得BTK的选择性和功效，我们设计了一系列新型的II型BTK抑制剂，它们可以占据DFG-out构象诱导的变构口袋，并引入了靶向Cys481的亲电子战斗部。在本文中，我们描述了结构-活性关系（SAR），从而导致了一系列新的有效且选择性的哌嗪和四氢异喹啉连接的BTK 5-苯氧基-2-氨基吡啶不可逆抑制剂。化合物18g显示出良好的效能和选择性，并且在血液肿瘤细胞系中评估了其生物学活性。还在Raji异种移植小鼠模型中测试了18g的体内功效，与载剂相比，它显着减小了肿瘤大小，抑制率为46.8％。因此，我们提出了新颖，有效和选择性的不可逆抑制剂18g作为II型BTK抑制剂。
• Compounds and methods of use
  申请人：Tango Therapeutics, Inc.

  公开号：US11077101B1

  公开（公告）日：2021-08-03

  Compounds are provided according to Formula (I): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein X1, X2, X3, X4, Y, A, L1, L2, R1, R2, R5, m and n are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

  根据以下公式（I）提供化合物： 及其药学上可接受的盐，以及其药物组合物；其中X1、X2、X3、X4、Y、A、L1、L2、R1、R2、R5、m和n如本文所定义。本发明的化合物被认为对预防和治疗各种疾病条件有用。
• Substituted phenyl methanones
  申请人：Jolidon Synese

  公开号：US20060167023A1

  公开（公告）日：2006-07-27

  The present invention relates to compounds of general formula IA or IB wherein X 1 and X 2 are each independently N or C—R″ and R 1 , R 2 ,R 3 , R 4 , R 5 , and R 6 are as defined in the specification and to pharmaceutically acceptable acid addition salts thereof. The compounds can be used for the treatment of diseases related to the glycine transporter inhibitor, such as schizophrenia and Alzheimer's disease.

  本发明涉及一般式IA或IB的化合物，其中X1和X2分别独立地为N或C—R″，R1、R2、R3、R4、R5和R6如规范中所定义，并且其药学上可接受的酸盐。这些化合物可用于治疗与甘氨酸转运体抑制剂相关的疾病，如精神分裂症和阿尔茨海默病。