tefludazine | 80273-79-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: tefludazine
• 英文别名: 2-[4-[(1S,3R)-3-(4-fluorophenyl)-6-(trifluoromethyl)-2,3-dihydro-1H-inden-1-yl]piperazin-1-yl]ethanol
• CAS: 80273-79-6；85663-48-5；111768-75-3；111768-76-4
• 化学式: C₂₂H₂₄F₄N₂O
• 分子量: 408.439
• InChiKey: JSBWGXQXCRYYTG-CTNGQTDRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-溴-4-三氟甲基苯甲醛 在 哌啶 、 sodium tetrahydroborate 、 正丁基锂 、 氯化亚砜 、 硫酸 、 magnesium 、 溶剂黄146 作用下， 以 甲醇 、 乙醚 、 正己烷 、 甲苯 、 丁酮 为溶剂， 反应 44.0h， 生成 tefludazine
  参考文献：
  名称：

  Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans

  摘要：

  A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineethanol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2nM for inhibition of dopamine uptake.

  DOI：

  10.1021/jm00361a002

文献信息

• Indane derivatives and methods of preparation and treatment
  申请人：H. LUNDBECK A/S

  公开号：EP0183349A1

  公开（公告）日：1986-06-04

  Indane derivatives with the formula: wherein R1 is H, Halogen, an alkyl group having from one to three carbon atoms inclusive, methoxy, a methylthio-group, or a trifluoromethyl group, n is 2-4, X is O or S, Y is 0, CH2 or N-R2, where R2 is hydrogen or an (1-6 C) alkyl, (1-6 C) alkenyl or cycloalkyl-methyl group having from three to six carbon atoms, Z is -(Ch2)n-, n is 2 or 3 or Z is 1,2-phenylene optionally substituted with halogen or trifluoromethyl or Z = 1,2-C6H4CO- (to form a quinazolidinone or -thione ring system). U = N or C, geometric isomers thereof as well as pharmaceutically acceptable acid addition salts are potent 5-HT2 antagonists useful in the treatment of cardiovascular diseases including hypertension and anxiety. Methods for the preparation of said compounds are also described.

  式中的茚满衍生物： 其中 R1 是 H、卤素、含 1 至 3 个碳原子的烷基、甲氧基、甲硫基或三氟甲基、 n 为 2-4、 X 是 O 或 S、 Y 是 0、CH2 或 N-R2，其中 R2 是氢或 (1-6 C) 烷基、 (1-6C)烯基或环烷基甲基，具有 3 至 6 个碳原子。 至六个碳原子的 (1-6 C) 烷基、(1-6 C) 烯基或环烷基甲基、 Z 是-(Ch2)n-，n 是 2 或 3，或 Z 是被卤素或三氟甲基任选取代的 1,2-亚苯基。 或 Z = 1,2-C6H4CO-（形成喹唑啉酮或硫酮环系）。 U = N 或 C、 其几何异构体以及药学上可接受的酸加成盐是强效的 5-HT2 拮抗剂，可用于治疗心血管疾病，包括高血压和焦虑症。 还描述了制备上述化合物的方法。
• US4684650A
  申请人：——

  公开号：US4684650A

  公开（公告）日：1987-08-04
• Neuroleptic activity and dopamine-uptake inhibition in 1-piperazino-3-phenylindans
  作者：Klaus P. Boegesoe

  DOI：10.1021/jm00361a002

  日期：1983.7

  A series of 1-piperazino-3-phenylindans was synthesized and tested for neuroleptic and thymoleptic activity. Neuroleptic activity was found only in trans racemates and was associated with one of the enantiomers only. The potent and long-acting neuroleptic compound trans-4-[3-(4-fluorophenyl)-6-(trifluoromethyl)indan-1-yl]-1-piperazineethanol (Lu 18-012, tefludazine) was developed by systematic variation of structural components. Thymoleptic activity was optimized, especially with respect to dopamine-uptake inhibition. No geometrical stereoselectivity was found with regard to dopamine-uptake inhibition, but a high enantioselectivity could be demonstrated for both cis and trans racemates. The most potent compounds were 1-piperazino-3-(3,4-dichlorophenyl)indans with IC50 values of about 2nM for inhibition of dopamine uptake.