2,6-双三氟甲基-4-溴喹啉 | 35853-48-6

• 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
• 中文名称: 2,6-双三氟甲基-4-溴喹啉
• 英文名称: 2,6-Bis(trifluormethyl)-4-bromchinolin
• 英文别名: 4-bromo-2,6-bis(trifluoromethyl)quinoline；2,6-bis(trifluoromethyl)-4-bromoquinoline
• CAS: 35853-48-6
• 化学式: C₁₁H₄BrF₆N
• 分子量: 344.054
• InChiKey: IJCXJMWXDNLXDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  7

安全信息

• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 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-溴喹啉 、 N,N-二甲基甲酰胺 在 正丁基锂 作用下， 以 乙醚 、 正己烷 为溶剂， 反应 3.5h， 生成 2,6-bis(trifluoromethyl)quinoline-4-carbaldehyde
  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：

  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

文献信息

• Neue 4-Chinolinmethanderivate, ihre Herstellung und Verwendung zur Darstellung von Substanzen mit Arzneimittelwirkung
  申请人：BASF Aktiengesellschaft

  公开号：EP0049776A2

  公开（公告）日：1982-04-21

  Die vorliegende Erfindung betrifft 4-Chinolinmethan- Derivate der Formel l worin R' ein Wasserstoffatom oder ein Chloratom, R2 eine Trifluormethylgruppe oder ein Chloratom, R3 einen stickstoffhaltigen, cyclisch-ungesättigten oder acyclisch-gesättigten Rest mit bis zu 6 Kohlenstoffatomen, R4 ein Wasserstoffatom oder eine anionenstabilisierende Gruppe und R5 ein Wasserstoffatom, ein anionisches Zentrum oder einen Acetalrest mit bis zu 8 Kohlenstoffatomen darstellen, deren Herstellung und deren Verwendung zur Herstellung von 4-Chinolinmethanol-Derivaten.

  本发明涉及式 I 的 4-喹啉甲烷衍生物，其中 R' 代表氢原子或氯原子，R2 代表三氟甲基或氯原子，R3 代表含氮、环状不饱和或无环饱和基团，最多有 6 个碳原子，R4 代表氢原子或阴离子稳定基团，R5 代表氢原子、阴离子中心或乙缩醛基团，最多有 8 个碳原子，本发明的制备及其在制备 4-喹啉甲醇衍生物中的用途。
• Neue Chlormethylchinolin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung
  申请人：ALKALOIDA VEGYéSZETI GYáR

  公开号：EP0113432B1

  公开（公告）日：1993-03-17
• 4-Chinolinderivate und deren Herstellung
  申请人：F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft

  公开号：EP0103259B1

  公开（公告）日：1986-02-26
• US3953453A
  申请人：——

  公开号：US3953453A

  公开（公告）日：1976-04-27
• From Serendipity to Rational Antituberculosis Drug Discovery of Mefloquine-Isoxazole Carboxylic Acid Esters
  作者：Jialin Mao、Hai Yuan、Yuehong Wang、Baojie Wan、Marco Pieroni、Qingqing Huang、Richard B. van Breemen、Alan P. Kozikowski、Scott G. Franzblau

  DOI：10.1021/jm900340a

  日期：2009.11.26

  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.