(3S,4R)-4-甲基-3-氨基吡咯烷 | 113617-67-7

• 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: (3S,4R)-4-甲基-3-氨基吡咯烷
• 中文别名: (3S,4R)-4-甲基吡咯烷-3-胺
• 英文名称: trans-4-methyl-3-aminopyrrolidine
• 英文别名: (3S,4R)-4-methylpyrrolidin-3-amine
• CAS: 113617-67-7；113617-69-9；116729-74-9；144238-34-6；144238-35-7；149714-40-9
• 化学式: C₅H₁₂N₂
• 分子量: 100.164
• InChiKey: SLTMFXXAJKCIPQ-RFZPGFLSSA-N

物化性质

• 沸点：
  137 °C
• 密度：
  0.891
• 闪点：
  37 °C

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  7
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S,4R)-4-甲基-3-氨基吡咯烷 在 盐酸 作用下， 以 乙腈 为溶剂， 生成 7-((3R,4S)-3-Amino-4-methyl-pyrrolidin-1-yl)-4-oxo-1-thiazol-2-yl-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 2

  摘要：

  We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyI derivative (271) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (SS)-isomer (AG-7352, 3) of 271, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.

  DOI：

  10.1021/jm0304966

文献信息

• Fluoronaphthyridines and -quinolones as antibacterial agents. 3. Synthesis and structure-activity relationships of new 1-(1,1-dimethyl-2-fluoroethyl), 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl], and 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituted derivatives
  作者：P. Remuzon、D. Bouzard、P. Di Cesare、M. Essiz、J. P. Jacquet、J. R. Kiechel、B. Ledoussal、R. E. Kessler、J. Fung-Tomc

  DOI：10.1021/jm00105a006

  日期：1991.1

  prepared. Structure-activity relationship (SAR) studies indicated that the in vitro antibacterial potency was the following order: 1-(1,1-dimethyl-2-fluoroethyl) greater than 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl] greater than 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituents. In the quinolone series the monofluoro-tert-butyl derivatives were found to possess better in vitro antibacterial activity

  制备了一系列新型的N-1-（单-，-（二-和-（三氟叔丁基）喹诺酮）和-萘吡啶类化合物，结构-活性关系（SAR）研究表明，体外抗菌能力是顺序如下：1-（1,1-二甲基-2-氟乙基）大于1- [1-甲基-1-（氟甲基）-2-氟乙基]大于1- [1,1-（二氟甲基）-2-在喹诺酮系列中，发现单氟叔丁基衍生物具有比非氟化叔丁基等效物更好的体外抗菌活性，其中1-氟叔丁基取代衍生物的体内PD50值反映了药代动力学行为和口服吸收不完全。
• Fluoronaphthyridines and quinolones as antibacterial agents. 2. Synthesis and structure-activity relationships of new 1-tert-butyl 7-substituted derivatives
  作者：D. Bouzard、P. Di Cesare、M. Essiz、J. P. Jacquet、J. R. Kiechel、P. Remuzon、A. Weber、T. Oki、M. Masuyoshi

  DOI：10.1021/jm00167a010

  日期：1990.5

  A number of 7-substituted-1-tert-butyl-6-fluoroquinolone-3-carboxylic acids and 7-substituted-1-tert-butyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids have been prepared and tested for antibacterial activities. Among those the 7-aminopyrrolidinyl 20b and the 7-diazabicyclo naphthyridine 18b are the most potent compounds in vitro and in vivo. Physicochemical data and acute toxicity are also discussed

  已经制备了许多7-取代的1-叔丁基-6-氟喹诺酮-3-羧酸和7-取代的1-叔丁基-6-氟-1,8-萘啶-3-羧酸。经测试具有抗菌活性。其中7-氨基吡咯烷基20b和7-二氮杂双环萘啶18b是体外和体内最有效的化合物。还讨论了理化数据和急性毒性。考虑到体外和体内的微生物活性，低毒性和药代动力学特征，化合物18b BMY 40062表现出最有利的总体性能，并被选择用于临床评估。
• Quinoline derivatives, pharmaceutical composition and method of use
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US04886810A1

  公开（公告）日：1989-12-12

  The present invention relates to quinoline derivatives of the formula ##STR1## wherein Z is an amino group or a halogen atom, R is ##STR2## in which R.sub.1 is a hydrogen atom, a lower alkyl or haloalkyl group, R.sub.2 is a hydrogen atom or a lower alkyl group, R.sub.3 is a lower alkyl or haloalkyl group, R.sub.4 is a hydrogen atom or a lower alkyl group, R.sub.5 and R.sub.6 are the same or different and each represents a hydrogen atom or a lower alkyl group, or R.sub.5 and R.sub.6, together with the nitrogen atom to which they are attached, form a heterocyclic ring, and n is 0 or 1, with the proviso that when Z is an amino group, R is (B); and esters thereof and salts thereof and processes for preparation thereof. These compounds show excellent antibacterial activity and are useful antibacterial agents.

  本发明涉及式（I）的喹啉衍生物：其中Z是氨基或卤素原子，R是式（II）：其中R1是氢原子、低碳基或卤代低碳基，R2是氢原子或低碳基，R3是低碳基或卤代低碳基，R4是氢原子或低碳基，R5和R6相同或不同，分别代表氢原子或低碳基，或R5和R6与它们所连接的氮原子形成杂环环，n为0或1，但当Z是氨基时，R为（B）；以及它们的酯和盐以及其制备方法。这些化合物表现出优异的抗菌活性，是有用的抗菌剂。
• Synthesis and Structure−Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 1
  作者：Kyoji Tomita、Yasunori Tsuzuki、Koh-ichiro Shibamori、Masanori Tashima、Fumie Kajikawa、Yuji Sato、Shigeki Kashimoto、Katsumi Chiba、Katsuhiko Hino

  DOI：10.1021/jm010057b

  日期：2002.12.1

  In an attempt to search for clinically useful antitumor agents, we have discovered that a series of 1,1-disubstituted-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids possessed moderate cytotoxic activity.,We investigated the structure-activity relationships in this series of compounds by changing N-1 and C-7 positions and the core ring structure itself and evaluated the synthesized compounds against several murine and human tumor cell lines. These modifications led us to the following findings. (1) The 2-thiazolyl group at the N-1 position of the naphthyridine structure is the best substituent for antitumor activity. (2) Regarding core ring structure, the naphthyridine derivative is the most active followed by pyridopyrimidine analogue. (3) At the C-7 position, -aminopyrrolidine derivatives are more effective than other amines or thioether derivatives. Finally, the trans-3-amino-4-methoxypyrrolidinyl derivative (43j), and the 3-amino-3-methylpyrrolidinyl derivative (43f) as well as 3-aminopyrrolidinyl derivative (AT-3639, 1) were determined to be effective in in vitro and in vivo antitumor assays, and their activity was comparable to that of etoposide.