1-butyl-4-[3-(trifluoromethyl)phenyl]piperazine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-butyl-4-[3-(trifluoromethyl)phenyl]piperazine
• 化学式: C₁₅H₂₁F₃N₂
• 分子量: 286.34
• InChiKey: IGYMDPIINSNIPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  6.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  三乙烯二胺 、 正溴丁烷 、 3-碘三氟甲苯 在 copper(l) iodide 、 potassium tert-butylate 作用下， 以 二甲基亚砜 为溶剂， 反应 4.0h， 以74%的产率得到1-butyl-4-[3-(trifluoromethyl)phenyl]piperazine
  参考文献：
  名称：

  Synthesis of N-alkyl-N′-aryl-piperazines via copper-catalyzed C–N bond formation

  摘要：

  An efficient copper-catalyzed tandem synthesis of N-alkyl-N'-aryl-piperazines from 1,4-diazabicyclo[2.2.2]octane, alkyl halides, and aryl halides in the presence of copper(I) iodide and potassium tert-butoxide in DMSO is described. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.tetlet.2014.08.045

文献信息

• 1-PHENYLALCOXY-2-BETA-PHENYLETHYL DERIVATIVES AS P-GLYCOPROTEIN (P-GP) INHIBITORS USEFUL IN DRUG RESISTANCE EVENTS
  申请人：Berardi Francesco

  公开号：US20090093493A1

  公开（公告）日：2009-04-09

  The invention relates to a new class of compounds, which are 1-phenylalcoxy-2-β-phenylethyl derivatives, as P-glycoprotein (P-GP) inhibitors. These compounds are useful in drug resistance events. They have been shown able to inhibit in a dose-dependent manner Glycoprotein-P (P-gp) activity in cell lines in which the expression of said glycoprotein is very high, like Caco-2 (human colon cancer) cells and MCF7/Adr (adriamycin-resistant human breast carcinoma) cells. The invention also relates to methods of production and the utilization of such compounds as medicaments useful in the treatment of states linked to the difficulty for some drugs to cross the blood-brain barrier (BBB) and generally within the context of the problems of drug resistance induced by chemotherapy agents.

  该发明涉及一类新化合物，即1-苯基羟基-2-β-苯乙基衍生物，作为P-糖蛋白（P-GP）抑制剂。这些化合物在药物耐药事件中很有用。已经证明它们能够以剂量依赖的方式抑制细胞系中的糖蛋白-P（P-gp）活性，其中所述糖蛋白的表达非常高，如Caco-2（人类结肠癌）细胞和MCF7/Adr（阿霉素耐药的人类乳腺癌）细胞。该发明还涉及生产方法和利用这类化合物作为药物的方法，用于治疗与某些药物跨越血脑屏障（BBB）困难相关的状态，以及在化疗药物引起的药物耐药问题背景下的一般情况。
• QUINOLINE-4-CARBOXAMIDE AS NK-2 AND NK-3 RECEPTOR ANTAGONISTS
  申请人：Giardina Arnaldo Maria Giuseppe

  公开号：US20070197546A1

  公开（公告）日：2007-08-23

  A compound, or a solvate or a salt thereof, of formula (I): wherein, Ar is an optionally substituted aryl or a C 5-7 cycloalkdienyl group, or a C 5-7 cycloalkyl group or an optionally substituted single or fused ring aromatic heterocyclic group,; R is C 1-6 alkyl, C 3-7 cycloalkyl, C 3-7 cycloalkylalkyl, optionally substituted phenyl or phenyl C 1-6 alkyl, an optionally substituted five-membered heteroaromatic ring comprising up to four heteroatoms selected from O and N, hydroxy C 1-6 alkyl, amino C 1-6 alkyl, C 1-6 alkylaminoalkyl, di C 1-6 alkylaminoalkyl, C 1-6 acylaminoalkyl, C 1-6 alkoxyalkyl, C 1-6 alkylcarbonyl, carboxy, C 1-6 alkoxycarbonyl, C 1-6 alkoxycarbonyl C 1-6 alkyl, aminocarbonyl, C 1-6 alkylaminocarbonyl, di C 1-6 alkylaminocarbonyl, halogeno C 1-6 alkyl; or R is a group —(CH 2 ) p — wherein p is 2 or 3 which group forms a ring with a carbon atom of Ar; R 1 represents hydrogen or up to four optional substituents selected from the list consisting of: C 1-6 alkyl, C 1-6 alkenyl, aryl, C 1-6 alkoxy, hydroxy, halogen, nitro, cyano, carboxy, carboxamido, sulphonamido, C 1-6 alkoxycarbonyl, trifluoromethyl, acyloxy, phthalimido, amino or mono- and di-C 1-6 alkylamino; R 2 represents a moiety —(CH 2 ) n —NY 1 Y 2 wherein n is an integer in the range of from 1 to 9, Y 1 and Y 2 are independently selected from hydrogen; C 1-6 -alkyl; C 1-6 alkyl substituted with hydroxy, C 1-6 alkylamino or bis (C 1-6 alkyl) amino; C 1-6 -alkenyl; aryl or aryl-C 1-6 -alkyl or Y 1 and Y 2 together with the nitrogen atom to which they are attached represent an optionally substituted N-linked single or fused ring heterocyclic group; R 3 is branched or linear C 1-6 alkyl, C 3-7 cycloalkyl, C 4-7 cycloalkylalkyl, optionally substituted aryl, or an optionally substituted single or fused ring aromatic heterocyclic group; and R4 represents hydrogen or C 1-6 alkyl; a pharmaceutical composition comprising such a compound, process for preparing such a compound and the use of such a compound in medicine.

  化合物，或其溶剂化合物或盐，其化学式为（I）：其中，Ar是可选择取代的芳基或C5-7环烯基基团，或C5-7环烷基团或可选择取代的单环或融合环芳杂环基团；R是C1-6烷基，C3-7环烷基，C3-7环烷基烷基，可选择取代的苯基或苯基C1-6烷基，包含最多四个杂原子（O和N）的可选择取代的五元杂环芳香环，羟基C1-6烷基，氨基C1-6烷基，C1-6烷基氨基烷基，二C1-6烷基氨基烷基，C1-6酰胺基烷基，C1-6烷氧基烷基，C1-6烷基羰基，羧基，C1-6烷氧羰基，C1-6烷氧羰基C1-6烷基，氨基羰基，C1-6烷基氨基羰基，二C1-6烷基氨基羰基，卤代C1-6烷基；或R是一个基团-（CH2）p-，其中p为2或3，该基团与Ar的一个碳原子形成环；R1表示氢或最多四个可选择的取代基，选自以下列表：C1-6烷基，C1-6烯基，芳基，C1-6烷氧基，羟基，卤素，硝基，氰基，羧基，羧酰胺基，磺酰胺基，C1-6烷氧羰基，三氟甲基，酰氧基，邻苯二甲酰亚胺基，氨基或单-和二-C1-6烷基氨基；R2表示一个基团-（CH2）n-NY1Y2，其中n是1到9的整数，Y1和Y2独立选择自氢，C1-6烷基，C1-6烷基取代羟基，C1-6烷基氨基或双（C1-6烷基）氨基，C1-6烯基，芳基或芳基-C1-6烷基，或Y1和Y2与它们所连接的氮原子一起表示可选择取代的N-连接单环或融合环杂环基团；R3是支链或线性C1-6烷基，C3-7环烷基，C4-7环烷基烷基，可选择取代的芳基，或可选择取代的单环或融合环芳杂环基团；R4表示氢或C1-6烷基；包括这种化合物的药物组合物，制备这种化合物的方法以及在医学上使用这种化合物的用途。
• Synthesis of N-alkyl-N′-aryl-piperazines via copper-catalyzed C–N bond formation
  作者：Issa Yavari、Mohammad J. Bayat、Majid Ghazanfarpour-Darjani

  DOI：10.1016/j.tetlet.2014.08.045

  日期：2014.10

  An efficient copper-catalyzed tandem synthesis of N-alkyl-N'-aryl-piperazines from 1,4-diazabicyclo[2.2.2]octane, alkyl halides, and aryl halides in the presence of copper(I) iodide and potassium tert-butoxide in DMSO is described. (C) 2014 Published by Elsevier Ltd.