苯乙胺,b-(2,2-二乙氧基乙基)-2-氟- | 115031-80-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 苯乙胺,b-(2,2-二乙氧基乙基)-2-氟-
• 英文名称: 4,4-Diethoxy-2-(2-fluoro-phenyl)-butylamine
• 英文别名: 4,4-Diethoxy-2-(2-fluorophenyl)butan-1-amine
• CAS: 115031-80-6
• 化学式: C₁₄H₂₂FNO₂
• 分子量: 255.333
• InChiKey: QCJSCLCSGWHPGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  44.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  苯乙胺,b-(2,2-二乙氧基乙基)-2-氟- 在 吡啶 、 盐酸 、 戊醇 、 盐酸羟胺 、 sodium 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 (2R,7S,8aS)-2-(2-Fluoro-phenyl)-octahydro-indolizin-7-ylamine
  参考文献：
  名称：

  Substituted benzamides with conformationally restricted side chains. 2. Indolizidine derivatives as central dopamine receptor antagonists

  摘要：

  The substituted benzamides metoclopramide (1) and clebopride (3) are stimulants of gastric motility. They are also central dopamine receptor antagonists with 3 being the more potent. This is presumed to be due to an additional interaction of its N-benzyl group with the receptor. The effect of restricting the conformation of this group by replacing the N-benzylpiperidine side chain of 3 by phenyl-substituted quinolizidines and indolizidines has been investigated. Only the indolizidines had significant activity, the nature of which depended upon the orientation of the phenyl substituent. The 2 alpha-phenyl isomers 5d-h were potent central dopamine D2 receptor antagonists with 5h showing selectivity for the limbic system. The 2 beta-phenyl isomer 5c was a gastric motility stimulant devoid of significant central dopamine receptor antagonist activity. Implications on receptor models are discussed.

  DOI：

  10.1021/jm00117a008
• 作为产物：
  描述：

  2-氟苯基乙腈 在 aluminium hydride 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 53.0h， 生成 苯乙胺,b-(2,2-二乙氧基乙基)-2-氟-
  参考文献：
  名称：

  Substituted benzamides with conformationally restricted side chains. 2. Indolizidine derivatives as central dopamine receptor antagonists

  摘要：

  The substituted benzamides metoclopramide (1) and clebopride (3) are stimulants of gastric motility. They are also central dopamine receptor antagonists with 3 being the more potent. This is presumed to be due to an additional interaction of its N-benzyl group with the receptor. The effect of restricting the conformation of this group by replacing the N-benzylpiperidine side chain of 3 by phenyl-substituted quinolizidines and indolizidines has been investigated. Only the indolizidines had significant activity, the nature of which depended upon the orientation of the phenyl substituent. The 2 alpha-phenyl isomers 5d-h were potent central dopamine D2 receptor antagonists with 5h showing selectivity for the limbic system. The 2 beta-phenyl isomer 5c was a gastric motility stimulant devoid of significant central dopamine receptor antagonist activity. Implications on receptor models are discussed.

  DOI：

  10.1021/jm00117a008

文献信息

• Azabicyclobenzamides, their preparation and their pharmaceutical compositions
  申请人：BEECHAM GROUP PLC

  公开号：EP0094744A1

  公开（公告）日：1983-11-23

  A compound of formula (I), or a pharmaceutically acceptable salt, N-oxide or solvent adduct thereof: wherein: R1 is C1-6 alkoxy, C1-6 alkylthio or, together with R6 is C1-2 alkylene, and one of R2, R3 and R4 is hydrogen and the other two together are C1-2 alkylenedioxy, or the other two are the same or different and are selected from the class of hydrogen. halogen, trifluoromethyl. C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio. C1-7 acyl, C, 7 acylamino. C1-6 alkylsulphonyl, C1-6 alkylsulphinyl hydroxy, nitro or amino, aminocarbonyl or aminosulphonyl optionally N-substituted by one or two C1-6 alkyl, C3-8 cycloalkyl, phenyl or phen C1-4 alkyl groups or optionally N-disubstituted by C4-5 polymethylene, or R, and R2 together are C1-2 alkylenedioxy, and R3 and R4 together are C1-2 alkylenedioxy or R3 and R4 are the same or different and are selected from the previously defined class of substituents; R5 is hydrogen or as defined with R1; R6 is hydrogen or C1-6 alkyl; and Ar is phenyl or thien-2-yl or thien-3-yl, optionally substituted by one or two groups, which are the same or different selected from C1-4 alkoxy, trifluoromethyl, halogen, carboxy, esterified carboxy or C1-4 alkyl optionally substituted by hydroxy, C1-4alkoxy, carboxy, esterified carboxy or in vivo hydrolysable C1-4 acyloxy. Ar being in the 3β configuration as defined in formula (VIII) ; and Ar may also have the a-configuration when one of R2, R3 and R4 is hydrogen and the other two are independently selected from optionally substituted amino or aminosulphonyl as defined, C1-6 alkylsulphonyl or C1-6 alkylsulphinyl; or R1 and R2 together are C1-2 alkylenedioxy and R3 and R4 are independently selected from the same group of substituents, compositions thereof and processes therefor.

  式 (I) 的化合物或其药学上可接受的盐、N-氧化物或溶剂加合物： 其中 R1为 C1-6烷氧基、C1-6烷硫基或与 R6 一起为 C1-2 亚烷基，R2、R3 和 R4 中的一个为氢，另外两个一起为 C1-2 亚烷基二氧基，或另外两个相同或不同且选自氢、卤素、三氟甲基、C1-6 烷基、C1-6 烷氧基、C1-6 烷硫基、C1-6 亚烷基二氧基、C1-6 烷硫基、C1-6 亚烷基二氧基、C1-6 烷硫基C1-6烷基，C1-6烷氧基，C1-6烷硫基。C1-7酰基、C, 7酰氨基。C1-6烷基磺酰基、C1-6烷基亚磺酰基 羟基、硝基或氨基、氨基羰基或氨基磺酰基，可任选被一个或两个 C1-6 烷基、C3-8 环烷基、苯基或苯 C1-4 烷基 N-取代，或任选被 C4-5 聚亚甲基 N-取代，或 R 和 R2 同为 C1-2 烷二氧基，R3 和 R4 同为 C1-2 烷二氧基，或 R3 和 R4 相同或不同，且选自前面定义的取代基类别； R5 是氢或与 R1 所定义的相同； R6 是氢或 C1-6 烷基；以及 Ar 是苯基或噻吩-2-基或噻吩-3-基，任选被一个或两个相同或不同的基团取代，这些基团选自 C1-4 烷氧基、三氟甲基、卤素、羧基、酯化羧基或任选被羟基、C1-4 烷氧基、羧基、酯化羧基或体内可水解的 C1-4 丙烯酸氧基取代的 C1-4 烷基。 当 R2、R3 和 R4 中的一个为氢，另外两个独立地选自任选取代的氨基或胺磺酰基（如定义）、C1-6 烷基磺酰基或 C1-6 烷基亚磺酰基时，Ar 为式（VIII）中定义的 3β 构型；Ar 也可具有 a 构型；或 R1 和 R2 共同为 C1-2 烷二氧基，R3 和 R4 独立选自同一组取代基、其组合物及其工艺。
• KING, FRANK D.;HADLEY, MICHAEL S.;MCCLELLAND, CHRISTINE M., J. MED. CHEM., 31,(1988) N 9, C. 1708-1712
  作者：KING, FRANK D.、HADLEY, MICHAEL S.、MCCLELLAND, CHRISTINE M.

  DOI：——

  日期：——
• US4559346A
  申请人：——

  公开号：US4559346A

  公开（公告）日：1985-12-17
• Substituted benzamides with conformationally restricted side chains. 2. Indolizidine derivatives as central dopamine receptor antagonists
  作者：Frank D. King、Michael S. Hadley、Christine M. McClelland

  DOI：10.1021/jm00117a008

  日期：1988.9

  The substituted benzamides metoclopramide (1) and clebopride (3) are stimulants of gastric motility. They are also central dopamine receptor antagonists with 3 being the more potent. This is presumed to be due to an additional interaction of its N-benzyl group with the receptor. The effect of restricting the conformation of this group by replacing the N-benzylpiperidine side chain of 3 by phenyl-substituted quinolizidines and indolizidines has been investigated. Only the indolizidines had significant activity, the nature of which depended upon the orientation of the phenyl substituent. The 2 alpha-phenyl isomers 5d-h were potent central dopamine D2 receptor antagonists with 5h showing selectivity for the limbic system. The 2 beta-phenyl isomer 5c was a gastric motility stimulant devoid of significant central dopamine receptor antagonist activity. Implications on receptor models are discussed.