1-甲基-4,5,6,6A-四氢-2H-吡咯并[2,3-c]吡咯 | 475468-76-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 中文名称: 1-甲基-4,5,6,6A-四氢-2H-吡咯并[2,3-c]吡咯
• 英文名称: 1,2,4,5,6,6a-hexahydro-1-methyl-1,5-diazapentalene
• 英文别名: 1-Methyl-1,2,4,5,6,6a-hexahydropyrrolo[3,4-b]pyrrole；1-methyl-4,5,6,6a-tetrahydro-2H-pyrrolo[3,4-b]pyrrole
• CAS: 475468-76-9
• 化学式: C₇H₁₂N₂
• mdl: MFCD12828638
• 分子量: 124.186
• InChiKey: UTMPINXFUYMIAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.714
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-甲基-4,5,6,6A-四氢-2H-吡咯并[2,3-c]吡咯 在 20percent aq. HCl 作用下， 以 乙腈 为溶剂， 生成 6-Fluoro-7-(1-methyl-2,4,6,6a-tetrahydropyrrolo[3,4-b]pyrrol-5-yl)-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylic acid;hydrochloride
  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
• 作为产物：
  描述：

  ethoxy N-(2-oxoethyl)-N-prop-2-ynylcarboxamide 在 盐酸 作用下， 以 甲苯 为溶剂， 反应 96.0h， 生成 1-甲基-4,5,6,6A-四氢-2H-吡咯并[2,3-c]吡咯
  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

• CGRP RECEPTOR ANTAGONISTS
  申请人：Stump Craig A.

  公开号：US20120010193A1

  公开（公告）日：2012-01-12

  Compounds of Formula (I) (wherein variables A 1 , A 2 , A 3 , ring-B, m, n, J, E 1 , E 2 , E 3 , R 5 , RPG and Y are as described herein), which are useful as antagonists of CGRP receptors, and useful in the treatment or prevention of diseases in which CGRP receptors are involved, such as headache, and in particular migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising the compounds of formula (I) and the use of these compounds and compositions in the prevention or treatment of diseases in which CGRP receptors are involved.

  公式（I）的化合物（其中变量A1，A2，A3，环B，m，n，J，E1，E2，E3，R5，RPG和Y如本文所述），其作为CGRP受体拮抗剂有用，并且在治疗或预防涉及CGRP受体的疾病方面有用，例如头痛，特别是偏头痛和集群头痛。本发明还涉及包含公式（I）化合物的制药组合物以及在预防或治疗涉及CGRP受体的疾病方面使用这些化合物和组合物。
• US20140275017A1
  申请人：——

  公开号：US20140275017A1

  公开（公告）日：2014-09-18
• US8778957B2
  申请人：——

  公开号：US8778957B2

  公开（公告）日：2014-07-15
• 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.