3-hydroxy-8-methylquinoline | 25369-30-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-hydroxy-8-methylquinoline
• 英文别名: 8-methylquinolin-3-ol；3-Hydroxy-8-methyl-chinolin
• CAS: 25369-30-6
• 化学式: C₁₀H₉NO
• 分子量: 159.188
• InChiKey: QKGIFAKVYMNTHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 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：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  8-methylquinoline-3-carboxaldehyde 在 双氧水 作用下， 以 水 、 溶剂黄146 为溶剂， 反应 1.0h， 以90%的产率得到3-hydroxy-8-methylquinoline
  参考文献：
  名称：

  通过dakin氧化方便地合成3-羟基喹啉：简捷的合成

  摘要：

  已经描述了通过对喹啉-3-羧醛的空前的Dakin氧化来方便地合成3-羟基喹啉。随后，报道了该方法在喹啉生物碱Jineol（1）的高产率合成中的应用。

  DOI：

  10.1016/j.tetlet.2020.152294

文献信息

• [EN] TRIAZOLE DERIVATIVES AND THEIR USE AS TANKYRASE INHIBITORS.<br/>[FR] DÉRIVÉS DE TRIAZOLE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA TANKYRASE
  申请人：GOLDING LOUISE

  公开号：WO2022008896A1

  公开（公告）日：2022-01-13

  The present invention relates to compounds of general formula (I), tautomers, stereoisomers, N-oxides, pharmaceutically acceptable salts and pro-drug thereof, to processes for their preparation, to pharmaceutical compositions containing such compounds and to their use in therapy: wherein: a dashed line indicates an optional bond; X represents: a 5- or 6-membered, unsaturated heterocyclic group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), C1-6 alkyl (e.g. C1-3 alkyl), C1-6 haloalkyl (e.g. C1-3 haloalkyl), C1-6 alkoxy (e.g. C1-3 alkoxy), -CN, -NO2, -N(R)2, and -SO2R (where each R is independently H or C1-6 alkyl, e.g. H or C1-3 alkyl); a C3-5 cycloalkyl group optionally substituted by one or more (e.g. 1 or 2) substituents independently selected from C1-6 alkyl (preferably C1-3 alkyl), C1-6 haloalkyl (e.g. C1-3 haloalkyl), and C1-6 alkoxy (e.g. C1-3 alkoxy); or an aryl group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), C1-6 alkyl (e.g. C1-3 alkyl), C1-6 haloalkyl (e.g. C1-3 haloalkyl), and C1-6 alkoxy (e.g. C1-3 alkoxy); Y represents: an aryl or heteroaryl group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), C1-6 alkyl (e.g. C1-3 alkyl), C1-6 haloalkyl (e.g. C1-3 haloalkyl), and C1-6 alkoxy (e.g. C1-3 alkoxy); a 5- or 6-membered, saturated heterocyclic group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from C1-6 alkyl (preferably C1-3 alkyl), C1-6 haloalkyl (e.g. C1-3 haloalkyl), and C1-6 alkoxy (e.g. C1-3 alkoxy); or a C3-6 cycloalkyl group optionally substituted by one or more (e.g. 1 or 2) substituents independently selected from C1-6 alkyl (preferably C1-3 alkyl), C1-6 haloalkyl (e.g. C1-3 haloalkyl), and C1-6 alkoxy (e.g. C1-3 alkoxy); and Z represents: an aryl group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), C1-6 alkyl (e.g. C1-3 alkyl), C1-6 haloalkyl (e.g. C1-3 haloalkyl), C1-6 alkoxy (e.g. C1-3 alkoxy), -CN, -NO2, -OH, -N(R' )2 (where each R1 is independently H or C1-6 alkyl, e.g. H or C1-3 alkyl), -SO2R2 (where R2 is H or C1-6 alkyl, e.g. H or C1-3 alkyl), -SO2N(R3)2 (where each R3 is independently H or C1-6 alkyl, e.g. H or C1-3 alkyl), and -C(0)N(R4)2 (where each R4 is independently H or C1-6 alkyl, e.g. H or C1-3 alkyl, or wherein both R4 groups, together with the intervening nitrogen atom, form a 3 to 6 membered saturated heterocyclic ring); or an unsaturated, 5- to 10-membered mono- or bicyclic heterocyclic group optionally substituted by one or more (e.g. 1, 2 or 3) substituents independently selected from halogen (i.e. F, Cl, Br, I), C1-6 alkyl (e.g. C1-3 alkyl), C1-6 haloalkyl (e.g. C1-3 haloalkyl), C1-6 alkoxy (e.g. C1-3 alkoxy), -CN, -NO2, -OH, -N(R')2 (where each R1 is independently H or C1-6 alkyl, e.g. H or C1-3 alkyl), -SO2R2 (where R2 is H or C1-6 alkyl, e.g. H or C1-3 alkyl), -SO2N(R3)2 (where each R3 is independently H or C1-6 alkyl, e.g. H or C1-3 alkyl), and -C(O)N(R4)2 (where each R4 is independently H or C1-6 alkyl, e.g. H or C1-3 alkyl, or wherein both R4 groups, together with the intervening nitrogen atom, form a 3 to 6 membered saturated heterocyclic ring); with the proviso: that when the compound is other than an N-oxide of formula (I), Z must be substituted by at least one substituent selected from -OH, -N(R3)2, -SO2N(R3)2 and -C(O)N(R4)2, preferably by at least one substituent selected from -OH, -SO2N(R3)2 and -C(O)N(R4)2. These compounds find particular use in the treatment and/or prevention of a disease or disorder responsive to inhibition of tankyrase 1 and/or 2, for example a disorder which is mediated by tankyrase 1 and/or 2 such as cancer.

  本发明涉及一般式(I)的化合物、互变异构体、立体异构体、N-氧化物、药学上可接受的盐及其前药，以及制备这些化合物的方法、含有这些化合物的制剂的制备方法以及它们在治疗中的应用：其中：虚线表示可选键；X表示：一个5-或6-成员的不饱和杂环基，可选地被一个或多个（例如1、2或3个）取代基独立地选自卤素（即F、Cl、Br、I）、C1-6烷基（例如C1-3烷基）、C1-6卤代烷基（例如C1-3卤代烷基）、C1-6烷氧基（例如C1-3烷氧基）、-CN、-NO2、-N（R）2和-SO2R（其中每个R独立地为H或C1-6烷基，例如H或C1-3烷基）；一个可选地被一个或多个（例如1或2个）取代基独立地选自C1-6烷基（优选为C1-3烷基）、C1-6卤代烷基（例如C1-3卤代烷基）和C1-6烷氧基（例如C1-3烷氧基）的C3-5环烷基；或一个可选地被一个或多个（例如1、2或3个）取代基独立地选自卤素（即F、Cl、Br、I）、C1-6烷基（例如C1-3烷基）、C1-6卤代烷基（例如C1-3卤代烷基）和C1-6烷氧基（例如C1-3烷氧基）的芳基基团；Y表示：一个可选地被一个或多个（例如1、2或3个）取代基独立地选自卤素（即F、Cl、Br、I）、C1-6烷基（例如C1-3烷基）、C1-6卤代烷基（例如C1-3卤代烷基）和C1-6烷氧基（例如C1-3烷氧基）的芳基或杂环芳基基团；一个可选地被一个或多个（例如1、2或3个）取代基独立地选自C1-6烷基（优选为C1-3烷基）、C1-6卤代烷基（例如C1-3卤代烷基）和C1-6烷氧基（例如C1-3烷氧基）的5-或6-成员饱和杂环基；或一个可选地被一个或多个（例如1或2个）取代基独立地选自C1-6烷基（优选为C1-3烷基）、C1-6卤代烷基（例如C1-3卤代烷基）和C1-6烷氧基（例如C1-3烷氧基）的C3-6环烷基；Z表示：一个可选地被一个或多个（例如1、2或3个）取代基独立地选自卤素（即F、Cl、Br、I）、C1-6烷基（例如C1-3烷基）、C1-6卤代烷基（例如C1-3卤代烷基）、C1-6烷氧基（例如C1-3烷氧基）、-CN、-NO2、-OH、-N（R'）2（其中每个R1独立地为H或C1-6烷基，例如H或C1-3烷基）、-SO2R2（其中R2为H或C1-6烷基，例如H或C1-3烷基）、-SO2N（R3）2（其中每个R3独立地为H或C1-6烷基，例如H或C1-3烷基）和-C（0）N（R4）2（其中每个R4独立地为H或C1-6烷基，例如H或C1-3烷基，或其中两个R4基与介于其间的氮原子一起形成3到6成员的饱和杂环环）；或一个可选地被一个或多个（例如1、2或3个）取代基独立地选自卤素（即F、Cl、Br、I）、C1-6烷基（例如C1-3烷基）、C1-6卤代烷基（例如C1-3卤代烷基）、C1-6烷氧基（例如C1-3烷氧基）、-CN、-NO2、-OH、-N（R'）2（其中每个R1独立地为H或C1-6烷基，例如H或C1-3烷基）、-SO2R2（其中R2为H或C1-6烷基，例如H或C1-3烷基）、-SO2N（R3）2（其中每个R3独立地为H或C1-6烷基，例如H或C1-3烷基）和-C（O）N（R4）2（其中每个R4独立地为H或C1-6烷基，例如H或C1-3烷基，或其中两个R4基与介于其间的氮原子一起形成3到6成员的饱和杂环环）的不饱和的5-到10-成员的单环或双环杂环基；但是，当化合物不是式(I)的N-氧化物时，Z必须被至少一个取代基取代，所述取代基选自-OH、-N（R3）2、-SO2N（R3）2和-C（O）N（R4）2，优选地被至少一个取代基选自-OH、-SO2N（R3）2和-C（O）N（R4）2。这些化合物在治疗和/或预防对坦克酰酶1和/或2的抑制有反应的疾病或障碍中特别有用，例如由坦克酰酶1和/或2介导的癌症。
• Multi‐Functional Oxidase Activity of CYP102A1 (P450BM3) in the Oxidation of Quinolines and Tetrahydroquinolines
  作者：Yushu Li、Luet L. Wong

  DOI：10.1002/anie.201904157

  日期：2019.7.8

  Tetrahydroquinoline, quinoline, and dihydroquinolinone are common core motifs in drug molecules. Screening of a 48‐variant library of the cytochrome P450 enzyme CYP102A1 (P450BM3), followed by targeted mutagenesis based on mutation‐selectivity correlations from initial hits, has enabled the hydroxylation of substituted tetrahydroquinolines, quinolines, and 3,4‐dihydro‐2‐quinolinones at most positions

  四氢喹啉，喹啉和二氢喹啉酮是药物分子中常见的核心基序。筛选细胞色素P450酶CYP102A1（P450BM3）的48个变体文库，然后基于初始命中的突变-选择性相关性进行定向诱变，使取代的四氢喹啉，喹啉和3,4-二氢-2-羟基化在两个环的大部分位置上，喹啉酮类以合成相关的比例（1.5 g L -1 天-1）。还观察到其他氧化酶活性，例如C-C键去饱和，芳构化和C-C键形成。这些酶变体在关键的活性位点残基S72，A82，F87，I263，E267，A328和A330处具有突变，为合成和药物发现这些构建基分子的氧官能化衍生物提供了直接且可持续的途径。
• 2,3-Dihydro-6-nitroimidazo[2,1-b]oxazoles
  申请人：Tsubouchi Hidetsugu

  公开号：US20060094767A1

  公开（公告）日：2006-05-04

  The present invention provides a 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole compound represented by the following general formula: wherein R 1 represents a hydrogen atom or C1-C6 alkyl group, n represents an integer of 0 to 6, R 2 represents a group —OR 3 or the like, and R 3 represents a hydrogen atom, C1-C6 alkyl group or the like, or R 1 and —(CH 2 ) n R 2 may bind to each other together with carbon atoms adjacent thereto through nitrogen atoms so as to form a spiro ring represented by the general formula (H): wherein R 41 is hydrogen, C1-C6 alkyl group or the like. The present compound has an excellent bactericidal action against Mycobacterium tuberculosis , multi-drug-resistant Mycobacterium tuberculosis , and atypical acid-fast bacteria.

  本发明提供了一种2,3-二氢-6-硝基咪唑并[2,1-b]噁唑化合物，其通式如下：其中，R1代表氢原子或C1-C6烷基，n代表0到6的整数，R2代表—OR3或类似的基团，R3代表氢原子、C1-C6烷基或类似的基团，或者R1和—(CH2)nR2可以通过相邻的碳原子通过氮原子结合在一起形成一个螺环，其通式为（H）：其中，R41为氢、C1-C6烷基或类似的基团。该化合物对结核分枝杆菌、多药耐药结核分枝杆菌和非典型酸性快速细菌具有优异的杀菌作用。
• 2,3-DIHYDRO-6-NITROIMIDAZO 2,1-b OXAZOLES
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP1555267A1

  公开（公告）日：2005-07-20

  The present invention provides a 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole compound represented by the following general formula: wherein R1 represents a hydrogen atom or C1-C6 alkyl group, n represents an integer of 0 to 6, R2 represents a group -OR3 or the like, and R3 represents a hydrogen atom, C1-C6 alkyl group or the like, or R1 and -(CH2)nR2 may bind to each other together with carbon atoms adjacent thereto through nitrogen atoms so as to form a spiro ring represented by the general formula (H): wherein R41 is hydrogen, C1-C6 alkyl group or the like. The present compound has an excellent bactericidal action against Mycobacterium tuberculosis, multi-drug-resistant Mycobacterium tuberculosis, and a typical acid-fast bacteria.

  本发明提供了由以下通式代表的 2，3-二氢-6-硝基咪唑并[2，1-b]恶唑化合物： 其中R1代表氢原子或C1-C6烷基，n代表0至6的整数，R2代表基团-OR3或类似基团，R3代表氢原子、C1-C6烷基或类似基团，或者R1和-(CH2)nR2可以通过氮原子与相邻的碳原子相互结合，从而形成通式(H)代表的螺环： 其中 R41 为氢、C1-C6 烷基或类似基团。本化合物对结核分枝杆菌、多重耐药结核分枝杆菌和典型的耐酸细菌有很好的杀菌作用。
• 2,3-dihydro-6-nitroimidazo[2,1-b]oxazoles compound
  申请人：OTSUKA PHARMACEUTICAL CO., LTD.

  公开号：EP2570418A2

  公开（公告）日：2013-03-20

  The present invention provides a 2,3-dihydro-6-nitroimidazo[2,1-b]oxazole compound represented by the following general formula: wherein R1 represents a hydrogen atom or C1-C6 alkyl group, n represents an integer of 0 to 6, R2 represents a group -OR3 or the like, and R3 represents a hydrogen atom, C1-C6 alkyl group or the like, or R1 and -(CH2)nR2 may bind to each other together with carbon atoms adjacent thereto through nitrogen atoms so as to form a spiro ring represented by the general formula (H): wherein R41 is hydrogen, C1-C6 alkyl group or the like. The present compound has an excellent bactericidal action against Mycobacterium tuberculosis, multi-drug-resistant Mycobacterium tuberculosis, and atypical acid-fast bacteria.

  本发明提供了一种由以下通式表示的 2,3-二氢-6-硝基咪唑并[2,1-b]恶唑化合物： 其中R1代表氢原子或C1-C6烷基，n代表0至6的整数，R2代表基团-OR3或类似基团，R3代表氢原子、C1-C6烷基或类似基团，或者R1和-(CH2)nR2可以通过氮原子与相邻的碳原子相互结合，从而形成通式(H)代表的螺环： 其中 R41 为氢、C1-C6 烷基或类似基团。本化合物对结核分枝杆菌、多重耐药结核分枝杆菌和非典型耐酸菌有很好的杀菌作用。