5-甲基异喹啉-1(2H)-酮 | 24188-72-5

• 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 - 异喹啉及其衍生物
• 中文名称: 5-甲基异喹啉-1(2H)-酮
• 英文名称: 5-methyl-1(2H)-isoquinolinone
• 英文别名: 5-methylisoquinolin-1(2H)-one；5-methyl-2H-isoquinolin-1-one
• CAS: 24188-72-5
• 化学式: C₁₀H₉NO
• 分子量: 159.188
• InChiKey: WSXOURRQDMFDRD-UHFFFAOYSA-N

物化性质

• 沸点：
  400.5±45.0 °C(Predicted)
• 密度：
  1.150±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 海关编码：
  2933790090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  5-甲基异喹啉-1(2H)-酮 在 palladium on activated charcoal 氢气 作用下， 以 溶剂黄146 为溶剂， 25.0 ℃ 、344.74 kPa 条件下， 以73%的产率得到5-甲基-3,4-二氢异喹啉-1(2H)-酮
  参考文献：
  名称：

  3,4-二氢-1（2 H）-异喹啉酮的合成

  摘要：

  介绍了制备规模合成目标3,4-dihydro-1（2 H）-isoquinolinones 1-3的方法。通过Schmidt重排在容易获得的茚满酮前体上制备化合物1和2，但是总产率较低。制备这类化合物的更好方法是通过Curtius重排序列大规模合成2来举例说明。因此，在三丁胺存在下，由前体8原位形成的异氰酸苯乙烯基异氰酸酯进行高温热环化反应，得到相应的1（2 H）-异喹啉酮（9 ）。9的催化氢化以65％的总收率提供了所需的3,4-二氢-5-甲基-1（2 H）-异喹啉酮（2）。将市售的5-羟基-1（2H）-异喹啉酮前体10进行类似的还原，然后进行O-烷基化/胺化序列，以良好的总产率得到了靶3。路线行进通过Curtius重排被推荐用于其它的3,4-二氢-1-（2-的大规模合成ħ）-异喹啉酮。仅当使苯甲环内的取代基或敏感官能团失活导致中间体异氰酸酯的高温闭环效率低下时，才可以选择施密特重排方案。

  DOI：

  10.1002/jhet.5570380424
• 作为产物：
  描述：

  间甲基苯甲酸 在 氯化亚砜 、 硫酸 、 potassium carbonate 作用下， 以 苯 为溶剂， 反应 90.0h， 生成 5-甲基异喹啉-1(2H)-酮
  参考文献：
  名称：

  Folate analogs. 35. Synthesis and biological evaluation of 1-deaza, 3-deaza, and bridge-elongated analogs of N10-propargyl-5,8-dideazafolic acid

  摘要：

  Structural modifications at the pyrimidine ring and at the C-9,N-10-bridge region of the thymidylate synthase (TS) inhibitors N-10-propargyl-5,8-dideazafolate (1; PDDF; CB 3717), 2-desamino-N10-propargyl-5,8-dideazafolate (2, DPDDF), and 2-desamino-2-methyl-N-10-propargyl-5,8-dideazafolate (3, DMPDDF) have been carried out. Methods for the synthesis of 2-desamino-N-10-propargyl-1,5,8-trideazafolate (4), 2-desamino-2-methyl-N-10-propargyl-3,5,8-trideazafolate (5a), and 2-desamino-2-methyl-N10-propargyl-5,8-dideaza-1,2-dihydrofolate (6) have been developed. The bridge-extended analogues isohomo-PDDF (7) and isohomo-DMPDDF (8) contain an additional methylene group interposed between N-10 and the phenyl ring of 1 and 3, respectively. All new compounds were evaluated as inhibitors of TS and the growth of tumor cells in culture. Selected analogues were tested as substrates of folylpolyglutamate synthetase (FPGS) and striking differences in substrate activity were observed among these compounds, indicating that structural modifications at the pyrimidine ring of classical antifolates profoundly influence their polyglutamylation. Enzyme inhibition data established that both N1 and N3-H of the pyrimidine ring are essential for efficient binding of quinazoline-type antifolates to human TS.

  DOI：

  10.1021/jm00113a011

文献信息

• Synthesis of Isoquinolones by Sequential Suzuki Coupling of 2-Halobenzonitriles with Vinyl Boronate Followed by Cyclization
  作者：Saul Jaime-Figueroa、Michael J. Bond、J. Ignacio Vergara、Jake C. Swartzel、Craig M. Crews

  DOI：10.1021/acs.joc.1c00472

  日期：2021.6.18

  A novel, facile, and expeditious two-step synthesis of 3,4-unsubstituted isoquinolin-1(2H)-ones from a Suzuki cross-coupling between 2-halobenzonitriles and commercially available vinyl boronates followed by platinum-catalyzed nitrile hydrolysis and cyclization is described.

  通过2-卤代苯甲腈和市售乙烯基硼酸酯之间的 Suzuki 交叉偶联，然后铂催化的腈水解和环化，一种新颖、简便且快速的两步合成 3,4-未取代的异喹啉-1(2 H )-酮被描述。
• [EN] PYRAZOLOPYRIDINE DERIVATIVES FOR THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE PYRAZOLOPYRIDINE POUR LE TRAITEMENT DU CANCER
  申请人：GENENTECH INC

  公开号：WO2017205538A1

  公开（公告）日：2017-11-30

  The present invention relates to a compound formula (I): and to salts thereof, wherein R1, R2X, and Y have any of the values defined herein, and compositions and uses thereof. The compounds are useful as inhibitors of CBP and/or EP300. Also included are pharmaceutical compositions comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof, and methods of using such compounds and salts in the treatment of various CBP and/or EP300-mediated disorders such as cancer, inflammatory disorders and autoimmune diseases.

  本发明涉及一种化合物公式（I）及其盐，其中R1、R2X和Y具有本文中定义的任何值，以及其组合物和用途。这些化合物可用作CBP和/或EP300的抑制剂。还包括包含公式（I）化合物或其药学上可接受的盐的药物组合物，以及在治疗各种CBP和/或EP300介导的疾病，如癌症、炎症性疾病和自身免疫疾病中使用这些化合物和盐的方法。
• [EN] HEPATITIS C VIRUS INHIBITORS<br/>[FR] INHIBITEURS DU VIRUS DE L'HEPATITE C
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2003099274A1

  公开（公告）日：2003-12-04

  Hepatitis C virus inhibitors are disclosed having the general formula:(I) wherein R1, R2, R3, R', B, Y and X are described in the description. Compositions comprising the compounds and methods for using the compounds toinhibit HCV are also disclosed.

  丙型肝炎病毒抑制剂公开了具有以下通式：其中R1、R2、R3、R'、B、Y和X在描述中有所描述。还公开了包含该化合物的组合物以及使用该化合物抑制HCV的方法。
• CANNABINOID RECEPTOR MODULATORS
  申请人：KULKARNI Sanjeev Anant

  公开号：US20130178457A1

  公开（公告）日：2013-07-11

  Compounds of Formula (I) along with processes for their preparation that are useful for treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of cannabinoid (CB) receptors. Methods of treating, managing and/or lessening the diseases, disorders, syndromes or conditions associated with the modulation of cannabinoid (CB) receptors of Formula (I).

  公式（I）的化合物以及用于制备这些化合物的方法，可用于治疗、管理和/或减轻与大麻素（CB）受体调节相关的疾病、紊乱、综合症或症状。治疗、管理和/或减轻与公式（I）的大麻素（CB）受体调节相关的疾病、紊乱、综合症或症状的方法。
• New Pyridinones and Isoquinolinones as Inhibitors of the Bromodomain BRD9
  申请人：Boehringer Ingelheim International GmbH

  公开号：US20180044335A1

  公开（公告）日：2018-02-15

  The present invention encompasses compounds of general formula (I) wherein the groups R 1 to R 9 , X 1 and X 2 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation, e.g. cancer, pharmaceutical preparations containing such compounds and their uses as a medicament.

  本发明涵盖了一般式（I）的化合物，其中基团R1至R9，X1和X2的含义如权利要求和说明书中所述。本发明的化合物适用于治疗由细胞过度或异常增殖所特征化的疾病，例如癌症，含有这种化合物的制药制剂以及它们作为药物的用途。