1,1-dimethylethyl (3S)-3-(2-methylpropylamino)pyrrolidine-1-carboxylate | 813447-22-2

• 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: 1,1-dimethylethyl (3S)-3-(2-methylpropylamino)pyrrolidine-1-carboxylate
• 英文别名: tert-butyl (3S)-3-(isobutylamino)pyrrolidine-1-carboxylate；tert-Butyl(3S)-3-(isobutylamino)pyrrolidine-1-carboxylate；tert-butyl (3S)-3-(2-methylpropylamino)pyrrolidine-1-carboxylate
• CAS: 813447-22-2
• 化学式: C₁₃H₂₆N₂O₂
• 分子量: 242.362
• InChiKey: AVRBSOQDODWUEU-NSHDSACASA-N

物化性质

• 沸点：
  315.9±35.0 °C(Predicted)
• 密度：
  0.99±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl (3S)-3-(2-methylpropylamino)pyrrolidine-1-carboxylate 、 2-异丙基苯甲酰氯 在 三乙胺 作用下， 生成 tert-butyl (S)-3-(N-isobutyl-2-isopropylbenzamido)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  N-[(3S)-Pyrrolidin-3-yl]benzamides as novel dual serotonin and noradrenaline reuptake inhibitors: Impact of small structural modifications on P-gp recognition and CNS penetration

  摘要：

  The structure-activity relationship and the synthesis of novel N-[(3S)-pyrrolidin-3-yl]benzamides as dual serotonin and noradrenaline monoamine reuptake inhibitors (SNRI) is described. Preferred compound 9 aka PF-184,298 is a potent SNRI with good selectivity over dopamine reuptake inhibition (DRI), good in vitro metabolic stability, weak CYP inhibition and drug-like physicochemical properties consistent with CNS target space. Evaluation in an in vivo preclinical model of stress urinary incontinence showed 9 significantly increased urethral tone at free plasma concentrations consistent with its in vitro primary pharmacology. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.049
• 作为产物：
  描述：

  异丁醛 、 (s)-(-)-N-叔丁氧羰基-3-氨基吡咯烷 在 钯 作用下， 以 甲醇 为溶剂， 反应 2.0h， 生成 1,1-dimethylethyl (3S)-3-(2-methylpropylamino)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  3-Aminopyrrolidines as inhibitors of monoamine uptake

  摘要：

  本发明提供了式（I）化合物及其药学上可接受的盐，用于抑制一个或多个生理活性单胺（血清素、去甲肾上腺素和多巴胺）的摄取。

  公开号：

  US20060270713A1

文献信息

• [EN] 3-AMINOPYRROLIDINES AS INHIBITORS OF MONOAMINE UPTAKE<br/>[FR] 3-AMINOPYRROLIDINES UTILISEES COMME INHIBITEURS DE L'APPORT DE MONOAMINE
  申请人：LILLY CO ELI

  公开号：WO2005000811A1

  公开（公告）日：2005-01-06

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, which are useful for the inhibition of the uptake of one or more physiologically active monoamines (serotonin, norepinephrine, and dopamine).

  本发明提供了式（I）的化合物及其药学上可接受的盐，用于抑制一个或多个生理活性单胺（5-羟色胺、去甲肾上腺素和多巴胺）的摄取。
• [EN] N-PYRROLIDIN-3-YL-AMIDE DERIVATIVES AS SEROTONIN AND NORADRENALINE RE-UPTAKE INHIBITORS<br/>[FR] DERIVES DE N-PYRROLIDIN-3-YL-AMIDE EN TANT QU'INHIBITEURS DU RECAPTAGE DE LA SEROTONINE ET DE LA NORADRENALINE
  申请人：PFIZER LTD

  公开号：WO2004110995A1

  公开（公告）日：2004-12-23

  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-Cl-4alkyl or het-Cl-4alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C1- 8allkyl, C1-8alkoxy, OH, halo, CF3, OCF3, SCF3, hydroxy-Cl-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-Cl-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-S­C1-4alkyl; 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.

  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。
• 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.

  化合物公式（I）及其医药和/或兽医可接受的衍生物，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，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*表示手性中心。本发明化合物表现出作为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实用性，例如尿失禁。
• N-Pyrrolidin-3YL-Amide Derivatives As Serotonin and Noradrenalin Re-Uptake Inhibitors
  申请人：Fish Paul Vincent

  公开号：US20090239928A1

  公开（公告）日：2009-09-24

  A compound of Formula (I) and pharmaceutically and/or veterinarily acceptable derivatives thereof, wherein: R 1 is H, C 1-6 alkyl, —C(A)D, 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 allkyl, C 1-8 alkoxy, OH, halo, CF 3 , OCHF 2 , OCF3, 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; A is S or O; D is H, C 1-6 alkyl, aryl, het, aryl-C 1-4 alkyl or het-C 1-4 alkyl; R 2 represents aryl 1 or het 1 , each of which is substituted by at least one substituent independently selected from B, provided that when R 2 is substituted by halo then it is also substituted with at least one other substituent independently selected from B other than halo; B represents aryl 2 , het 2 , Oaryl 2 , Ohet 2 , Sarl 2 , Shet 2 , SC 1-6 alkyl, halogen, CHF 2 , OCHF 2 , CF 2 CF 3 , CH 2 CF 3 , CF2CH 3 , aryl 2 -C 1-4 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-C 1-4 alkyl, C 3-6 cycloalkylC 1-4 alkoxy, C 3-6 cycloalkyl-O—C 1-4 alkyl, C 3-6 cycloalkyl-C 1-4 alkoxy-C 1-4 alkyl, OC 3-6 cycloalkyl, SC 3-6 cycloalkyl; wherein the aryl 2 and het 2 groups are optionally substituted by at least one group selected from C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, OC 3-6 cycloalkyl, halo, CN, OH, CF 3 , CHF 2 , OCF 3 , OCHF 2 , hydroxyC 1 $alkyl, C 1-4 alkoxy-C 1-4 alkyl, SC 1-6 alkyl and SCF 3 ; 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 centre; R 3 is H, C 1-6 alkyl, C 3-8 cycloalkyl, C 3-8 cycloalkylC 1-6 alkyl, aryl 3 , het 3 , aryl 3 -C 1-4 alkyl or het 3 -C 1-4 alkyl, wherein the C 3-8 cycloalkyl, aryl 3 or het 3 groups are optionally substituted by at least one substituent independently selected from C 1-6 alkyl, C 1-6 alkoxy, CN, 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; at each occurrence aryl, aryl 1 , aryl 2 and aryl 3 independently represent phenyl, naphthyl, anthracyl or phenanthryl; het 1 represents an aromatic 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to an aryl group; at each occurrence het, het 2 , and het 3 independently represents an aromatic or non-aromatic 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 5- or 6-membered carbocyclic group or a second 4-, 5- or 6membered heterocycle which contains at least one N, O or S heteroatom.

  公式（I）的化合物及其药学和/或兽医学上可接受的衍生物，其中：R1为H，C1-6烷基，-C（A）D，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取代，该取代基独立地选择自C1-8烷基，C1-8烷氧基，OH，卤素，CF3，OCHF2，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；A为S或O；D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；R2代表芳基1或杂环基1，每个都被至少一个取代基独立地选择自B，但当R2被卤素取代时，它还被至少一个取代基独立地选择自B，该取代基不是卤素；B代表芳基2，杂环基2，O芳基2，Ohet2，S芳基2，Shet2，SC1-6烷基，卤素，CHF2，OCHF2，CF2CF3，CH2CF3，CF2CH3，芳基2-C1-4烷基，C3-6环烷基，C3-6环烷基-C1-4烷基，C3-6环烷基C1-4烷氧基，C3-6环烷基-O-C1-4烷基，C3-6环烷基-C1-4烷氧基-C1-4烷基，OC3-6环烷基，SC3-6环烷基；其中芳基2和杂环基2可以选择地被至少一个基团取代，所述基团选择自C1-6烷基，C3-6环烷基，C1-6烷氧基，OC3-6环烷基，卤素，CN，OH，CF3，CHF2，OCF3，OCHF2，羟基C1$烷基，C1-4烷氧基-C1-4烷基，SC1-6烷基和SCF3；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*表示手性中心；R3为H，C1-6烷基，C3-8环烷基，C3-8环烷基C1-6烷基，芳基3，杂环基3，芳基3-C1-4烷基或杂环基3-C1-4烷基，其中C3-8环烷基，芳基3或杂环基3可以选择地被至少一个取代基取代，该取代基独立地选择自C1-6烷基，C1-6烷氧基，CN，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；在每次出现中，芳基，芳基1，芳基2和芳基3独立地表示苯基，萘基，蒽基或菲基；het1表示至少含有一个N，O或S杂原子的芳香5-或6元杂环，可选择地与芳基团融合；在每次出现中，het，het2和het3独立地表示至少含有一个N，O或S杂原子的芳香或非芳香4、5或6元杂环，可选择地与5-或6元杂环碳环基或含有至少一个N，O或S杂原子的第二个4、5或6元杂环融合。
• 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。