(S)-1-(trifluoroacetyl)pyrrolidin-3-yl amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (S)-1-(trifluoroacetyl)pyrrolidin-3-yl amine
• 英文别名: (S)-1-(3-aminopyrrolidin-1-yl)-2,2,2-trifluoroethanone；1-[(3S)-3-aminopyrrolidin-1-yl]-2,2,2-trifluoroethanone
• 化学式: C₆H₉F₃N₂O
• 分子量: 182.145
• InChiKey: ZTUXUCVZUZQGGS-BYPYZUCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  正丁醛 、 (S)-1-(trifluoroacetyl)pyrrolidin-3-yl amine 在 palladium 10% on activated carbon 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、415.01 kPa 条件下， 反应 18.0h， 生成 (3S)-N-butyl-1-(trifluoroacetyl)pyrrolidin-3-amine
  参考文献：
  名称：

  [EN] N-PYRROLIDIN-3-YL-AMIDE DERIVATIVES AS SEROTONIN AND NORADRENALINE RE-UPTAKE INHIBITORS
  [FR] DERIVES DE N-PYRROLIDIN-3-YL-AMIDE EN TANT QU'INHIBITEURS DU RECAPTAGE DE LA SEROTONINE ET DE LA NORADRENALINE

  摘要：

  公式（I）的化合物及其在药学和/或兽医学上可接受的衍生物中，其中R1为H，C1-6烷基，-C(X)Y，C3-8环烷基，芳基，杂环基，芳基-Cl-4烷基或杂基-Cl-4烷基，其中环烷基，芳基或杂基可选择地被至少一个取代基取代，所述取代基可独立地选择自C1-8烷基，C1-8烷氧基，OH，卤素，CF3，OCF3，SCF3，羟基-Cl-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基；R2为芳基或杂芳基，每个可选择地被至少一个取代基取代，所述取代基可独立地选择自C1-8烷基，C1-8烷氧基，OH，卤素，CF3，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基；R3为C1-6烷基，C3-8环烷基，C3-8环烷基-C1-6烷基，芳基，杂环基，芳基-Cl-4烷基或杂基-C1-4烷基，其中环烷基，芳基或杂基可选择地被至少一个取代基取代，所述取代基可独立地选择自C1-6烷基，C1-6烷氧基，OH，卤素，CF3，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基；X为S或O；Y为H，C1-6烷基，芳基，杂环基，芳基-C1-4烷基或杂基-C1-4烷基；n为1或2，但当n为1时，m为0或1，当n为2时，m为0，其中如果m为0，则*表示一个手性中心。本发明的化合物表现出作为5-羟色胺和去甲肾上腺素再摄取抑制剂的活性，因此在多种治疗领域中具有用途，例如尿失禁。

  公开号：

  WO2004110995A1

文献信息

• [EN] AMIDE DERIVATIVES AS SELECTIVE SEROTONIN RE-UPTAKE INHIBITORS<br/>[FR] DERIVES D'AMIDE EN TANT QU'INHIBITEURS SELECTIFS DU RECAPTAGE DE LA SEROTONINE
  申请人：PFIZER LTD

  公开号：WO2004111003A1

  公开（公告）日：2004-12-23

  The present invention relates to compounds of formula (I), wherein R1 is selected from: (a) (C1-C6)alkyl, optionally substituted by 1-3 substituents, each independently selected from: (i) CF3, OH, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy and halo; (ii) Phenyl, optionally fused with phenyl or cyclohexyl, said phenyl or fused phenyl optionally substituted with 1-3 groups selected from (C1-C6)alkyl, (C1-C6)alkyl ester, OH and halo; and (b) (C3-C6)cycloalkyl, optionally fused with (C5-C7)cycloalkyl, said cycloalkyl or fused cycloalkyl optionally substituted by OH, (C1-C6)alkyl, (C1-C6)alkoxy and halo. R2 is Phenyl, optionally fused to (C4-C6)cycloalkyl, phenyl or pyridyl, said phenyl or fused phenyl moiety optionally substituted with 1-3 groups each independently selected from (C1-C6)alkyl, (C1-C6)alkoxy, halo and OH. n is 1 to 2 and pharmaceutically acceptable salts, solvates or polymorphs thereof; With the proviso that when n is 2 and R1 is 2-(3,4-dimethoxylphenyl)-1-ethyl, 3,3­diphemyl-1-propyl or 2,4-difluorophenyl, then R2 cannot be 4-trifluoromethoxyphenyl, 2,4,6-trimethoxyphenyl, 4-acetoxyphenyl or 2,4-difluorophenyl; which are a class of selective serotonin re-uptake inhibitors (SSRIs).

  本发明涉及式(I)的化合物，其中R1从以下选项中选择：(a) (C1-C6)烷基，可选地被1-3个取代基取代，每个取代基独立地从以下选项中选择：(i) CF3，OH，(C1-C6)烷基，(C3-C6)环烷基，(C1-C6)烷氧基和卤素；(ii) 苯基，可选地与苯基或环己基融合，所述苯基或融合苯基可选地被1-3个取代基取代，所述取代基独立地从(C1-C6)烷基，(C1-C6)烷基酯，OH和卤素中选择；和(b) (C3-C6)环烷基，可选地与(C5-C7)环烷基融合，所述环烷基或融合环烷基可选地被OH，(C1-C6)烷基，(C1-C6)烷氧基和卤素取代。R2为苯基，可选地融合到(C4-C6)环烷基，苯基或吡啶基，所述苯基或融合苯基基团可选地被1-3个取代基取代，每个取代基独立地从(C1-C6)烷基，(C1-C6)烷氧基，卤素和OH中选择。n为1至2，以及其药学上可接受的盐、溶剂化合物或多形体；但是当n为2且R1为2-(3,4-二甲氧基苯基)-1-乙基，3,3-二苯基-1-丙基或2,4-二氟苯基时，R2不能为4-三氟甲氧基苯基，2,4,6-三甲氧基苯基，4-乙酰氧基苯基或2,4-二氟苯基；这些是一类选择性5-羟色胺再摄取抑制剂（SSRIs）。
• Novel compounds
  申请人：Fish Vincent Paul

  公开号：US20050137229A1

  公开（公告）日：2005-06-23

  A compound of Formula (I) and pharmaceutically and/or veterinarily acceptable derivatives thereof, wherein R 1 is H, C 1-6 alkyl, —C(X)Y, C 3-8 cycloalkyl, aryl, het, aryl-C 1-4 alkyl or het-C 1-4 alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C 1-8 alkyl, C 1-8 alkoxy, OH, halo, CF 3 , OCF 3 , SCF 3 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl and C 1-4 alkyl-S—C 1-4 alkyl; R 2 is aryl or heteroaryl, each optionally substituted by at least one substituent independently selected from C 1-8 alkyl, C 1-8 alkoxy, OH, halo, CF 3 , OCF 3 , SCF 3 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl and C 1-4 alkyl-S—C 1-4 alkyl; R 3 is C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl-C 1-6 alkyl, aryl, het, aryl-C 1-4 alkyl or het-C 1-4 alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C 1-6 alkyl, C 1-6 alkoxy, OH, halo, CF 3 , OCF 3 , SCF 3 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy —C 1-6 alkyl and C 1-4 alkyl-S—C 1-4 alkyl; X is S or O; Y is H, C 1-6 alkyl, aryl, het, aryl-C 1-4 alkyl or het-C 1-4 alkyl; and n is 1 or 2, provided that when n is 1, m is 0 or 1 and when n is 2, m is 0, wherein if m is 0, then * represents a chiral center. The compounds of the invention exhibit activity as both serotonin and noradrenaline re-uptake inhibitors and therefore have utility in a variety of therapeutic areas, for example urinary incontinence.

  公式（I）及其药学和/或兽医学上可接受的衍生物的化合物，其中R1为H，C1-6烷基，-C（X）Y，C3-8环烷基，芳基，杂环基，芳基-C1-4烷基或杂环基-C1-4烷基，其中环烷基，芳基或杂环基可选地由至少一个取代基独立选择自C1-8烷基，C1-8烷氧基，OH，卤素，CF3，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基取代；R2为芳基或杂环基，每个可选地由至少一个取代基独立选择自C1-8烷基，C1-8烷氧基，OH，卤素，CF3，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基取代；R3为C1-6烷基，C3-8环烷基，C3-8环烷基-C1-6烷基，芳基，杂环基，芳基-C1-4烷基或杂环基-C1-4烷基，其中环烷基，芳基或杂环基可选地由至少一个取代基独立选择自C1-6烷基，C1-6烷氧基，OH，卤素，CF3，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基取代；X为S或O；Y为H，C1-6烷基，芳基，杂环基，芳基-C1-4烷基或杂环基-C1-4烷基；n为1或2，前提是当n为1时，m为0或1，当n为2时，m为0，其中如果m为0，则*表示手性中心。本发明的化合物表现出作为5-羟色胺和去甲肾上腺素再摄取抑制剂的活性，因此在多种治疗领域具有用途，例如尿失禁。
• Amide derivatives as selective serotonin re-uptake inhibitors
  申请人：Andrews David Mark

  公开号：US20050014789A1

  公开（公告）日：2005-01-20

  The present invention relates to compounds of formula (I), wherein R 1 is selected from: (a) (C 1 -C 6 )alkyl, optionally substituted by 1-3 substituents, each independently selected from: (i) CF 3 , OH, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy and halo. (ii) Phenyl, optionally fused with phenyl or cyclohexyl, said phenyl or fused phenyl optionally substituted with 1-3 groups selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )alkyl ester, OH and halo; and (b) (C 3 -C 6 )cycloalkyl, optionally fused with (C 5 -C 7 )cycloalkyl, said cycloalkyl or fused cycloalkyl optionally substituted by OH, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy and halo. R 2 is Phenyl, optionally fused to (C 4 -C 6 )cycloalkyl, phenyl or pyridyl, said phenyl or fused phenyl moiety optionally substituted with 1-3 groups each independently selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, halo and OH; n is 1 to 2; and pharmaceutically acceptable salts, solvates or polymorphs thereof; With the proviso that when n is 2 and R 1 is 2-(3,4-dimethoxylphenyl)-1-ethyl, 3,3-diphenyl-1-propyl or 2,4-difluorophenyl, then R 2 cannot be 4-trifluoromethoxyphenyl, 2,4,6-trimethoxyphenyl, 4-acetoxyphenyl or 2,4-difluorophenyl; which are a class of selective serotonin re-uptake inhibitors (SSRIs).

  本发明涉及式（I）的化合物，其中R1选自：（a）（C1-C6）烷基，可选地被1-3个取代基取代，每个取代基独立地选自：（i）CF3，OH，（C1-C6）烷基，（C3-C6）环烷基，（C1-C6）烷氧基和卤素；（ii）苯基，可选地与苯基或环己基融合，所述苯基或融合苯基可选地被1-3个选自（C1-C6）烷基，（C1-C6）烷酯，OH和卤素的基团取代；和（b）（C3-C6）环烷基，可选地与（C5-C7）环烷基融合，所述环烷基或融合环烷基可选地被OH，（C1-C6）烷基，（C1-C6）烷氧基和卤素取代。R2为苯基，可选地融合到（C4-C6）环烷基、苯基或吡啶基上，所述苯基或融合苯基基团可选地被1-3个独立选自（C1-C6）烷基，（C1-C6）烷氧基，卤素和OH的基团取代；n为1到2；以及其药学上可接受的盐、溶剂或多型性；但当n为2且R1为2-(3,4-二甲氧基苯基)-1-乙基、3,3-二苯基-1-丙基或2,4-二氟苯基时，则R2不能是4-三氟甲氧基苯基、2,4,6-三甲氧基苯基、4-乙酰氧基苯基或2,4-二氟苯基；这是一类选择性5-羟色胺再摄取抑制剂（SSRI）。
• NOVEL COMPOUNDS
  申请人：Fish Paul Vincent

  公开号：US20080306123A1

  公开（公告）日：2008-12-11

  A compound of Formula (I) and pharmaceutically and/or veterinarily acceptable derivatives thereof, wherein R 1 is H, C 1-6 alkyl, —C(X)Y, C 3-8 cycloalkyl, aryl, het, aryl-C 1-4 alkyl or het-C 1-4 alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C 1-8 alkyl, C 1-8 alkoxy, OH, halo, CF 3 , OCF 3 , SCF 3 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl and C 1-4 alkyl-S—C 1-4 alkyl; R 2 is aryl or heteroaryl, each optionally substituted by at least one substituent independently selected from C 1-8 alkyl, C 1-8 alkoxy, OH, halo, CF 3 , OCF 3 , SCF 3 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl and C 1-4 alkyl-S—C 1-4 alkyl; R 3 is C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkyl-C 1-6 alkyl, aryl, het, aryl-C 1-4 alkyl or het-C 1-4 alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C 1-6 alkyl, C 1-6 alkoxy, OH, halo, CF 3 , OCF 3 , SCF 3 , hydroxy-C 1-6 alkyl, C 1-4 alkoxy-C 1-6 alkyl and C 1-4 alkyl-S—C 1-4 alkyl; X is S or O; Y is H, C 1-6 alkyl, aryl, het, aryl-C 1-4 alkyl or het-C 1-4 alkyl; and n is 1 or 2, provided that when n is 1, m is 0 or 1 and when n is 2, m is 0, wherein if m is 0, then * represents a chiral center. The compounds of the invention exhibit activity as both serotonin and noradrenaline re-uptake inhibitors and therefore have utility in a variety of therapeutic areas, for example urinary incontinence.

  公式（I）的化合物及其药学和/或兽医上可接受的衍生物，其中R1为H，C1-6烷基，-C（X）Y，C3-8环烷基，芳基，杂环基，芳基-C1-4烷基或杂环基-C1-4烷基，其中环烷基，芳基或杂环基可以选择地被至少一个取代基独立地选择自C1-8烷基，C1-8烷氧基，OH，卤素，CF3，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基；R2为芳基或杂环基，每个可以选择地被至少一个取代基独立地选择自C1-8烷基，C1-8烷氧基，OH，卤素，CF3，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基；R3为C1-6烷基，C3-8环烷基，C3-8环烷基-C1-6烷基，芳基，杂环基，芳基-C1-4烷基或杂环基-C1-4烷基，其中环烷基，芳基或杂环基可以选择地被至少一个取代基独立地选择自C1-6烷基，C1-6烷氧基，OH，卤素，CF3，OCF3，SCF3，羟基-C1-6烷基，C1-4烷氧基-C1-6烷基和C1-4烷基-S-C1-4烷基；X为S或O；Y为H，C1-6烷基，芳基，杂环基，芳基-C1-4烷基或杂环基-C1-4烷基；n为1或2，前提是当n为1时，m为0或1，当n为2时，m为0，其中如果m为0，则*表示手性中心。该发明的化合物表现出作为5-羟色胺和去甲肾上腺素再摄取抑制剂的活性，因此在各种治疗领域，例如尿失禁方面具有实用性。
• Compounds
  申请人：Pfizer Inc.

  公开号：US07378436B2

  公开（公告）日：2008-05-27

  A compound of Formula (I) and pharmaceutically and/or veterinarily acceptable derivatives thereof, wherein R1 is H, C1-6alkyl, —C(X)Y, C3-8cycloalkyl, aryl, het, aryl-C1-4alkyl or het-C1-4alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C1-8alkyl, C1-8alkoxy, OH, halo, CF3, OCF3, SCF3, hydroxy-C1-6alkyl, C1-4alkoxy-C1-6alkyl and C1-4alkyl-S—C1-4alkyl; R2 is aryl or heteroaryl, each optionally substituted by at least one substituent independently selected from C1-8alkyl, C1-8alkoxy, OH, halo, CF3, OCF3, SCF3, hydroxy-C1-6alkyl, C1-4alkoxy-C1-6alkyl and C1-4alkyl-S—C1-4alkyl; R3 is C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6alkyl, aryl, het, aryl-C1-4alkyl or het-C1-4alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C1-6alkyl, C1-6alkoxy, OH, halo, CF3, OCF3, SCF3, hydroxy-C1-6alkyl, C1-4alkoxy —C1-6alkyl and C1-4alkyl-S—C1-4alkyl; X is S or O; Y is H, C1-6alkyl, aryl, het, aryl-C1-4alkyl or het-C1-4alkyl; and n is 1 or 2, provided that when n is 1, m is 0 or 1 and when n is 2, m is 0, wherein if m is 0, then * represents a chiral center. The compounds of the invention exhibit activity as both serotonin and noradrenaline re-uptake inhibitors and therefore have utility in a variety of therapeutic areas, for example urinary incontinence.

  化合物公式（I）及其在药学和/或兽医学上可接受的衍生物中，其中R1为H、C1-6烷基、—C（X）Y、C3-8环烷基、芳基、杂环基、芳基-C1-4烷基或杂环基-C1-4烷基，其中环烷基、芳基或杂环基可以选用至少一个取代基独立地选自C1-8烷基、C1-8烷氧基、OH、卤素、CF3、OCF3、SCF3、羟基-C1-6烷基、C1-4烷氧基-C1-6烷基和C1-4烷基-S—C1-4烷基；R2为芳基或杂环基，每个都可以选用至少一个取代基独立地选自C1-8烷基、C1-8烷氧基、OH、卤素、CF3、OCF3、SCF3、羟基-C1-6烷基、C1-4烷氧基-C1-6烷基和C1-4烷基-S—C1-4烷基；R3为C1-6烷基、C3-8环烷基、C3-8环烷基-C1-6烷基、芳基、杂环基、芳基-C1-4烷基或杂环基-C1-4烷基，其中环烷基、芳基或杂环基可以选用至少一个取代基独立地选自C1-6烷基、C1-6烷氧基、OH、卤素、CF3、OCF3、SCF3、羟基-C1-6烷基、C1-4烷氧基-C1-6烷基和C1-4烷基-S—C1-4烷基；X为S或O；Y为H、C1-6烷基、芳基、杂环基、芳基-C1-4烷基或杂环基-C1-4烷基；n为1或2，但当n为1时，m为0或1，当n为2时，m为0，其中如果m为0，则*表示一个手性中心。本发明的化合物表现出作为5-羟色胺和去甲肾上腺素再摄取抑制剂的活性，因此在多种治疗领域中具有实用性，例如尿失禁。