3-氨基甲基-4-羟基-1-吡咯烷羧酸-1,1-二甲基乙酯 | 773826-73-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 3-氨基甲基-4-羟基-1-吡咯烷羧酸-1,1-二甲基乙酯
• 中文别名: N-Boc-3-氨甲基-4-羟基吡咯烷
• 英文名称: tert-butyl 3-(aminomethyl)-4-hydroxypyrrolidine-1-carboxylate
• CAS: 773826-73-6
• 化学式: C₁₀H₂₀N₂O₃
• mdl: MFCD11973748
• 分子量: 216.28
• InChiKey: AHJZEZIYOBGVSK-UHFFFAOYSA-N

物化性质

• 沸点：
  329.4±27.0 °C(Predicted)
• 密度：
  1.146

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  75.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-氨基甲基-4-羟基-1-吡咯烷羧酸-1,1-二甲基乙酯 在 甲醇 、 盐酸羟胺 、 三氧化硫吡啶 、 碳酸氢钠 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 乙酰氯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 乙腈 为溶剂， 反应 5.83h， 生成 gemifloxacin
  参考文献：
  名称：

  Novel Fluoroquinolone Antibacterial Agents Containing Oxime-Substituted (Aminomethyl)pyrrolidines:  Synthesis and Antibacterial Activity of 7-(4-(Aminomethyl)-3-(methoxyimino)pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro- 4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic Acid (LB20304)^,1

  摘要：

  New pyrrolidine derivatives, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been synthesized and coupled with various quinolinecarboxylic acids to produce a series of new fluoroquinolone antibacterials. These fluoroquinolones were found to possess potent antimicrobial activity against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Variations at the C-8 position of the quinolone nucleus included fluorine, chlorine, nitrogen, methoxy, and hydrogen atom substitution. The activity imparted to the substituted quinolone nucleus by the C-8 substituent was in the order F (C-5-NH2) > F (C-5-H) > naphthyridine > Cl = OMe = H against Gram-positive organisms. In the case of Gram-negative strains, activity was in the order F (C-5-NH2) > naphthyridine = F (C-5-H) > H > Cl > OMe. The advantages provided by the newly introduced oxime group of the quinolones were clearly demonstrated by their comparison to a desoximino compound 30. In addition, the oxime moiety greatly improved the pharmacokinetic parameters of the novel quinolones. Among these compounds, compound 20 (LB20304) showed the best in vivo efficacy and pharmacokinetic profile in animals, as well as good physical properties. The MICs (mu g/mL) of LB20304, compound 30, and ciprofloxacin against several test organisms are as follows: S. aureus 6538p (0.008, 0.031, and 0.13), methicillin resistant S. aureus 241 (4, 16, and 128), Streptococcus epidermidis 887E (0.008, 0.016, and 0.13), methicillin resistant S. epidermidis 178 (4, 32, and 128), Enterococcus faecalis 29212 (0.063, 0.13, and 1), Pseudomonas aeruginosa 1912E (0.25, 0.5, and 0.13), Escherichia coli 3190Y (0.008, 0.016, and 0.008), Enterobacter cloacae P99 (0.008, 0.031, and 0.008), Acinobacter calcoaceticus 15473 (0.063, 0.13, and 0.25). On the basis of these promising results, LB20304 was selected as a candidate for further evaluation.

  DOI：

  10.1021/jm970202e
• 作为产物：
  描述：

  N-tert-butoxycarbonyl-2-(2-cyanoethyl)aminoacetic acid ethyl ester 在 sodium tetrahydroborate 、 lithium aluminium tetrahydride 、 乙醇 、 sodium ethanolate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 生成 3-氨基甲基-4-羟基-1-吡咯烷羧酸-1,1-二甲基乙酯
  参考文献：
  名称：

  Novel Fluoroquinolone Antibacterial Agents Containing Oxime-Substituted (Aminomethyl)pyrrolidines:  Synthesis and Antibacterial Activity of 7-(4-(Aminomethyl)-3-(methoxyimino)pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro- 4-oxo-1,4-dihydro[1,8]naphthyridine-3-carboxylic Acid (LB20304)^,1

  摘要：

  New pyrrolidine derivatives, which bear an alkyloxime substituent in the 4-position and an aminomethyl substituent in the 3-position of the pyrrolidine ring, have been synthesized and coupled with various quinolinecarboxylic acids to produce a series of new fluoroquinolone antibacterials. These fluoroquinolones were found to possess potent antimicrobial activity against both Gram-negative and Gram-positive organisms, including methicillin resistant Staphylococcus aureus (MRSA). Variations at the C-8 position of the quinolone nucleus included fluorine, chlorine, nitrogen, methoxy, and hydrogen atom substitution. The activity imparted to the substituted quinolone nucleus by the C-8 substituent was in the order F (C-5-NH2) > F (C-5-H) > naphthyridine > Cl = OMe = H against Gram-positive organisms. In the case of Gram-negative strains, activity was in the order F (C-5-NH2) > naphthyridine = F (C-5-H) > H > Cl > OMe. The advantages provided by the newly introduced oxime group of the quinolones were clearly demonstrated by their comparison to a desoximino compound 30. In addition, the oxime moiety greatly improved the pharmacokinetic parameters of the novel quinolones. Among these compounds, compound 20 (LB20304) showed the best in vivo efficacy and pharmacokinetic profile in animals, as well as good physical properties. The MICs (mu g/mL) of LB20304, compound 30, and ciprofloxacin against several test organisms are as follows: S. aureus 6538p (0.008, 0.031, and 0.13), methicillin resistant S. aureus 241 (4, 16, and 128), Streptococcus epidermidis 887E (0.008, 0.016, and 0.13), methicillin resistant S. epidermidis 178 (4, 32, and 128), Enterococcus faecalis 29212 (0.063, 0.13, and 1), Pseudomonas aeruginosa 1912E (0.25, 0.5, and 0.13), Escherichia coli 3190Y (0.008, 0.016, and 0.008), Enterobacter cloacae P99 (0.008, 0.031, and 0.008), Acinobacter calcoaceticus 15473 (0.063, 0.13, and 0.25). On the basis of these promising results, LB20304 was selected as a candidate for further evaluation.

  DOI：

  10.1021/jm970202e

文献信息

• [EN] PROGRANULIN MODULATORS AND METHODS OF USING THE SAME<br/>[FR] MODULATEURS DE LA PROGRANULINE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ARKUDA THERAPEUTICS

  公开号：WO2020252222A1

  公开（公告）日：2020-12-17

  Provided herein are compounds that modulate progranulin and methods of using the compounds in progranulin-associated disorders, such as Frontotemporal dementia (FTD).

  本文件提供了调节颗粒蛋白的化合物及其在颗粒蛋白相关疾病中的使用方法，例如额颞痴呆（FTD）。
• [EN] GCN2 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE GCN2 ET LEURS UTILISATIONS
  申请人：MERCK PATENT GMBH

  公开号：WO2019148132A1

  公开（公告）日：2019-08-01

  The present invention provides compounds, compositions thereof, and methods of using the same.

  本发明提供了化合物、其组合物以及使用它们的方法。
• Compounds
  申请人：Cailleau Nathalie

  公开号：US20080221110A1

  公开（公告）日：2008-09-11

  Tricyclic nitrogen containing compounds and their use as antibacterials

  三环氮含化合物及其作为抗菌剂的用途
• Pyrrolo[3,2,1-ij]quinoline-4-one derivatives for treating tuberculosis
  申请人：GLAXO GROUP LIMITED

  公开号：EP1980251A1

  公开（公告）日：2008-10-15

  Tricyclic nitrogen-containing compounds of Formula (I) and pharmaceutically acceptable derivatives thereof: compositions containing them, their use in the treatment of tuberculosis, and methods for the preparation of such compounds.

  公式（I）中的三环含氮化合物及其药用可接受衍生物： 包含它们的组合物，它们在结核病治疗中的用途，以及制备这类化合物的方法。
• 一类咪唑并芳环类化合物的制备和应用
  申请人：上海轶诺药业有限公司

  公开号：CN111039946A

  公开（公告）日：2020-04-21

  本发明提供了一类咪唑并芳环类化合物的制备和应用，具体地，本发明提供了一种如下式I所示的化合物，其中，各基团的定义如说明书中所述。所述的化合物具有TRK激酶抑制活性，可以作为治疗TRK功能异常相关疾病的药物组合物。