rac-4-[(1S,3R,8aR)-3-(2,3-dimethoxyphenyl)hexahydro[1,3]oxazolo-[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline

• 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: rac-4-[(1S,3R,8aR)-3-(2,3-dimethoxyphenyl)hexahydro[1,3]oxazolo-[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline
• 英文别名: (1S,3R,8aR)-1-[2,8-bis(trifluoromethyl)quinolin-4-yl]-3-(2,3-dimethoxyphenyl)-3,5,6,7,8,8a-hexahydro-1H-[1,3]oxazolo[3,4-a]pyridine
• 化学式: C₂₆H₂₄F₆N₂O₃
• 分子量: 526.479
• InChiKey: OYHPBXOFXJWCGO-RVSNTGDXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  37
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  43.8
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,3-二甲氧基苯甲醛 、 mefloquine 在 Amberlyst 15 作用下， 以 甲苯 为溶剂， 以58%的产率得到rac-4-[(1S,3R,8aR)-3-(2,3-dimethoxyphenyl)hexahydro[1,3]oxazolo-[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline
  参考文献：
  名称：

  Mefloquine–oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: In vitro activity including against the multidrug-resistant tuberculosis strain T113

  摘要：

  Ten new mefloquine-oxazolidine derivatives, 4-[(1S,8aR)-3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (1: aryl = substituted phenyl) and 4-[(1S, 8aR)-3-(heteroaryl) hexahydro[1,3] oxazolo[3,4-a] pyridin-1-yl]-2,8-bis(trifluoromethyl) quinoline [2: heteroaryl = 5-nitrothien-2-yl (2a); 5-nitrofuran-2-yl (2b) and 4H-imidazol-2-yl) (2c)], have been synthesized and evaluated against Mycobacterium tuberculosis. Compounds 1f (aryl = 3-ethoxyphenyl), 1g (Ar = 3,4,5-(MeO)(3)-C6H2) and 2c were slightly more active than mefloquine (MIC = 33 mu M) with MICs = 24.5, 22.5 and 27.4, respectively, whereas compounds 1e (aryl = 3,4-(MeO)(2)-C6H3) and 2a (MICs = 11.9 and 12.1 mu M, respectively) were ca. 2.7 times more active than mefloquine, with a better tuberculostatic activity than the first line tuberculostatic agent ethambutol (MIC = 15.9). The compounds were also assayed against the MDR strain T113 and the same MICs were observed. Thus the new derivatives have advantages over such anti-TB drugs as isoniazid, rifampicin, ethambutol and ofloxacin, for which this strain is resistant. The most active compounds were not cytotoxic to Murine Macrophages Cells in a concentration near their MIC values. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.006

文献信息

• Mefloquine–oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: In vitro activity including against the multidrug-resistant tuberculosis strain T113
  作者：Raoni S.B. Gonçalves、Carlos R. Kaiser、Maria C.S. Lourenço、Flavio A.F.M. Bezerra、Marcus V.N. de Souza、James L. Wardell、Solange M.S.V. Wardell、Maria das Graças M.de O. Henriques、Thadeu Costa

  DOI：10.1016/j.bmc.2011.11.006

  日期：2012.1

  Ten new mefloquine-oxazolidine derivatives, 4-[(1S,8aR)-3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (1: aryl = substituted phenyl) and 4-[(1S, 8aR)-3-(heteroaryl) hexahydro[1,3] oxazolo[3,4-a] pyridin-1-yl]-2,8-bis(trifluoromethyl) quinoline [2: heteroaryl = 5-nitrothien-2-yl (2a); 5-nitrofuran-2-yl (2b) and 4H-imidazol-2-yl) (2c)], have been synthesized and evaluated against Mycobacterium tuberculosis. Compounds 1f (aryl = 3-ethoxyphenyl), 1g (Ar = 3,4,5-(MeO)(3)-C6H2) and 2c were slightly more active than mefloquine (MIC = 33 mu M) with MICs = 24.5, 22.5 and 27.4, respectively, whereas compounds 1e (aryl = 3,4-(MeO)(2)-C6H3) and 2a (MICs = 11.9 and 12.1 mu M, respectively) were ca. 2.7 times more active than mefloquine, with a better tuberculostatic activity than the first line tuberculostatic agent ethambutol (MIC = 15.9). The compounds were also assayed against the MDR strain T113 and the same MICs were observed. Thus the new derivatives have advantages over such anti-TB drugs as isoniazid, rifampicin, ethambutol and ofloxacin, for which this strain is resistant. The most active compounds were not cytotoxic to Murine Macrophages Cells in a concentration near their MIC values. (C) 2011 Elsevier Ltd. All rights reserved.