3-Pyrrolidinamine, 4-methoxy-, (3R,4R)-

• 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: 3-Pyrrolidinamine, 4-methoxy-, (3R,4R)-
• 英文别名: (3R,4R)-4-methoxypyrrolidin-3-amine
• 化学式: C₅H₁₂N₂O
• 分子量: 116.163
• InChiKey: GUCHNZPHITVHJH-RFZPGFLSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  47.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Pyrrolidinamine, 4-methoxy-, (3R,4R)- 在 lithium aluminium tetrahydride 、 L-酒石酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙腈 为溶剂， 反应 26.0h， 生成 (3S,4S)-1-benzyl-3-(N-tert-butoxycarbonyl)methylamino-4-methoxypyrrolidine
  参考文献：
  名称：

  Practical synthesis of (3S,4S)-3-methoxy-4-methylaminopyrrolidine

  摘要：

  Three synthetic methods for the preparation of (3S,4S)-3-methoxy-4-methylaminopyrrolidine, an important intermediate in the synthesis of the novel quinolone antitumor agent, AG-7352, have been developed. By one route, an efficient and large-scale preparation of the chiral pyrrolidine could be achieved through resolution of (+/-)-1-Boc-3-benzylamino-4-hydroxypyrrolidine, which is prepared from either 3-pyrroline or 1,4-dichloro-2-butene. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0957-4166(01)00530-4
• 作为产物：
  描述：

  (-)-(3R,4R)-3-amino-1-benzyl-4-methoxypyrrolidine 在 palladium on activated charcoal 氢气 作用下， 生成 3-Pyrrolidinamine, 4-methoxy-, (3R,4R)-
  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 1

  摘要：

  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.

  DOI：

  10.1021/jm010057b

文献信息

• 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
  作者：Yasunori Tsuzuki、Kyoji Tomita、Koh-ichiro Shibamori、Yuji Sato、Shigeki Kashimoto、Katsumi Chiba

  DOI：10.1021/jm0304966

  日期：2004.4.1

  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.
• IVATA, MASAYUKI;KIMURA, FUMIO;FUDZIVARA, JOSIMI;KATSUBEH, TEHTSUDZI
  作者：IVATA, MASAYUKI、KIMURA, FUMIO、FUDZIVARA, JOSIMI、KATSUBEH, TEHTSUDZI

  DOI：——

  日期：——
• Okada Tetsuo, Sato Hisao, Tsuji Teruji, Tsushima Tadahiko, Nakai Hiroshi,+, Chem. and Pharm. Bull., 41 (1993) N 1, S 132-138
  作者：Okada Tetsuo, Sato Hisao, Tsuji Teruji, Tsushima Tadahiko, Nakai Hiroshi,+

  DOI：——

  日期：——
• 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.
• Practical synthesis of (3S,4S)-3-methoxy-4-methylaminopyrrolidine
  作者：Yasunori Tsuzuki、Katsumi Chiba、Kazuhiro Mizuno、Kyoji Tomita、Kenji Suzuki

  DOI：10.1016/s0957-4166(01)00530-4

  日期：2001.11

  Three synthetic methods for the preparation of (3S,4S)-3-methoxy-4-methylaminopyrrolidine, an important intermediate in the synthesis of the novel quinolone antitumor agent, AG-7352, have been developed. By one route, an efficient and large-scale preparation of the chiral pyrrolidine could be achieved through resolution of (+/-)-1-Boc-3-benzylamino-4-hydroxypyrrolidine, which is prepared from either 3-pyrroline or 1,4-dichloro-2-butene. (C) 2002 Published by Elsevier Science Ltd.