2,6-双(三氟甲基)-4-羟基喹啉 | 35877-04-4

• 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
• 中文名称: 2,6-双(三氟甲基)-4-羟基喹啉
• 英文名称: 2,6-bis(trifluoromethyl)-4-quinolinol
• 英文别名: 4-Hydroxy-2,6-bis(trifluoromethyl)quinoline；2,6-bis(trifluoromethyl)quinolin-4-ol；2,6-bis(trifluoromethyl)-1H-quinolin-4-one
• CAS: 35877-04-4
• 化学式: C₁₁H₅F₆NO
• mdl: MFCD25542084
• 分子量: 281.157
• InChiKey: AOGNHURBEDTPIZ-UHFFFAOYSA-N

物化性质

• 熔点：
  280-290°C
• 沸点：
  305.9±37.0 °C(Predicted)
• 密度：
  1.542±0.06 g/cm3(Predicted)
• 溶解度：
  >42.2 [ug/mL]
• 稳定性/保质期：

  常规情况下不会分解，也没有危险反应。

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  8

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S26,S36,S37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2933499090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312+P330,P302+P352,P304+P340+P312,P305+P351+P338,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2,6-双(三氟甲基)-4-羟基喹啉 在 三溴化磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以77%的产率得到2,6-双三氟甲基-4-溴喹啉
  参考文献：
  名称：

  From Serendipity to Rational Antituberculosis Drug Discovery of Mefloquine-Isoxazole Carboxylic Acid Esters

  摘要：

  Both in vitro and in vivo metabolism studies suggested that 5-(2,8-bis(trifluoromethyl)quinolin-4-yloxymethyl)isoxazole-3-carboxylic acid ethyl ester (compound 3) with previously reported anti-tuberculosis activity is rapidly converted to two metabolites 3a and 3b. In order to improve the metabolic stability of this series, chemistry efforts were focused on the modification of the oxymethylene linker of compound 3 in the present study. Compound 9d with an alkene linker was found to be both more metabolically stable and more potent than compound 3, with a minimum inhibitory concentration (MIC) of 0.2 mu M and 2.6 mu M against replicating and nonreplicating Mycobaterium tuberculosis, respectively. These attributes make 9d ail interesting lead compound. A number of modifications were made to the structure of 9d, and it series of active Compounds were discovered. Although some neurotoxicity was observed at it high dosage, this new series was endowed with both improved in vitro anti-TB activity and metabolic stability in comparison to compound 3.

  DOI：

  10.1021/jm900340a
• 作为产物：
  描述：

  对三氟甲基苯胺 、 三氟乙酰乙酸乙酯 在 magnesium sulfate 、 溶剂黄146 、 dowtherm A 作用下， 以 乙醇 为溶剂， 反应 16.5h， 生成 2,6-双(三氟甲基)-4-羟基喹啉
  参考文献：
  名称：

  天然奎宁生物碱启发的新型喹啉衍生物的设计，合成和抗真菌评价

  摘要：

  受奎宁及其类似物的启发，我们设计，合成和评估了两个系列的喹啉小分子化合物（a和2a）和六个系列的喹啉衍生物（3a - f）的抗真菌活性。结果表明，化合物3e和3f系列表现出显着的杀真菌活性。值得注意的是，化合物3f-4（EC 50 = 0.41μg/ mL）和3f-28（EC 50 = 0.55μg/ mL）显示出优异的体外杀真菌活性和对菌核菌的有效体内治疗作用。初步机理研究表明，化合物3f-4和3f-28可能引起细胞膜通透性改变，活性氧的积累，线粒体膜电位的丧失以及有效抑制菌核菌的发芽和形成。这些结果表明，化合物3f-4和3f-28是对抗源自天然产物的核盘菌的新型潜在杀真菌剂。

  DOI：

  10.1021/acs.jafc.9b04224

文献信息

• [EN] CYCLOHEXYL-AZETIDINYL ANTAGONISTS OF CCR2<br/>[FR] ANTAGONISTES DU CCR2 À BASE DE CYCLOHEXYL-AZÉTIDINYLE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2011159854A1

  公开（公告）日：2011-12-22

  The present invention comprises compounds of Formula (I). Wherein: R1, R2, R4, J, Q, and A are as defined in the specification. The invention also comprises a method of preventing, treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is type II diabetes, obesity and asthma. The invention also comprises a method of inhibiting CCR2 activity in a mammal by administration of a therapeutically effective amount of at least one compound of Formula (I).

  本发明包括公式(I)的化合物。其中：R1、R2、R4、J、Q和A如说明书所述定义。本发明还包括预防、治疗或改善综合征、障碍或疾病的方法，其中所述综合征、障碍或疾病为2型糖尿病、肥胖和哮喘。本发明还包括通过管理治疗有效量的至少一种公式(I)化合物来抑制哺乳动物中的CCR2活性的方法。
• [EN] ANTIBIOTIC COMPOSITIONS<br/>[FR] COMPOSITIONS ANTIBIOTIQUES
  申请人：DARTMOUTH COLLEGE

  公开号：WO2017136642A1

  公开（公告）日：2017-08-10

  The present disclosure relates to compounds having antimicrobial activity, compositions comprising said compounds in combination with β-lactam antibiotics, and methods of using the compounds and compositions.

  本公开涉及具有抗微生物活性的化合物，包括这些化合物与β-内酰胺类抗生素结合的组合物，以及使用这些化合物和组合物的方法。
• Antibacterial activity of new substituted 4-N-alkylated-2-trifluoromethyl-quinoline analogues against sensitive and resistant Mycobacterium tuberculosis strains
  作者：Emerson Teixeira da Silva、Gabriel Fernandes de Andrade、Adriele da Silva Araújo、Maria Cristina Silva Lourenço、Marcus Vinícius Nora de Souza

  DOI：10.1016/j.ejps.2020.105596

  日期：2021.2

  resistant strain has aggravated the tuberculosis situation in the world, running out of control and hard to fight. We evaluate forty new quinoline analogues against sensitive and resistant Mycobacterium tuberculosis (Mtb). Methods; The compounds were obtained via synthesis and evaluated against sensitive strain ATCC 27294. Selected compounds were evaluated against resistant strains SR 2571/0215 and

  目标 抗药性菌株的出现加剧了世界结核病的状况，失去了控制，难以抵抗。我们评估了针对敏感和耐药结核分枝杆菌（Mtb）的40种新喹啉类似物。 方法; 通过合成获得化合物，并针对敏感菌株ATCC 27294进行评估。使用MABA方法，对选定的化合物针对SR 2571/0215和T113 / 09耐药菌株进行评估。选择更具活性的化合物，因为它们对人巨噬细胞具有潜在的细胞毒活性。 结果； 29种化合物对敏感菌株具有活性，而13种对抗性菌株具有活性。针对敏感菌株，最有前途的化合物是4c和4d（MIC分别为9和12μM）。对于抗药性菌株，化合物4a，4d显示出最佳结果（分别为MIC = 4和5μM）。活性化合物4a，4d，6d，7c，8d和10d在接近MIC的浓度下对宿主细胞无细胞毒性。复合的无细胞毒性4d对抗药性和敏感性Mtb最有效。 结论 这些发现有助于寻找敏感和耐药结核病的新生物活性化合物的相关信
• Proline derivatives and use thereof as drugs
  申请人：Kitajima Hiroshi

  公开号：US20050245538A1

  公开（公告）日：2005-11-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the γ-position of proline represented by the formula (I) wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗效果的化合物，其作用是通过DPP-IV的抑制作用，并且作为药物产品具有令人满意的效果。本发明人发现，在丙氨酸的γ位上引入取代基的衍生物具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。
• Proline derivatives and the use thereof as drugs
  申请人：——

  公开号：US20040106655A1

  公开（公告）日：2004-06-03

  The present invention aims at providing compounds having therapeutic effects due to a DPP-IV inhibitory action, and satisfactory as pharmaceutical products. The present inventors have found that derivatives having a substituent introduced into the &ggr;-position of proline represented by the formula (I) 1 wherein each symbol is as defined in the specification, have a potent DPP-IV inhibitory activity, and completed the present invention by increasing the stability.

  本发明旨在提供具有治疗作用的化合物，由于DPP-IV抑制作用而具有满意的药物产品。本发明人发现，具有引入取代基的脯氨酸γ-位置的衍生物，其化学式为(I)1，其中每个符号如规范中所定义，具有强效的DPP-IV抑制活性，并通过增加稳定性完成了本发明。