ethyl 2,4,6-trichloronicotinoylacetate | 174727-37-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 2,4,6-trichloronicotinoylacetate
• 英文别名: 2,4,6-trichloro-nicotinoylacetic acid ethyl ester；Ethyl 3-oxo-3-(2,4,6-trichloropyridin-3-yl)propanoate
• CAS: 174727-37-8
• 化学式: C₁₀H₈Cl₃NO₃
• 分子量: 296.537
• InChiKey: AHNSCKQCIZRKNL-UHFFFAOYSA-N

物化性质

• 沸点：
  353.1±37.0 °C(Predicted)
• 密度：
  1.460±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-氨基噻唑 、 原甲酸三乙酯 、 ethyl 2,4,6-trichloronicotinoylacetate 在 乙酸酐 作用下， 以 异丙醚 为溶剂， 反应 6.0h， 以58%的产率得到ethyl 2-(2,4,6-trichloro-3-nicotinoyl)-3-(2-thiazolylamino)acrylate
  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
• 作为产物：
  描述：

  2,4,6-三氯吡啶 在 正丁基锂 、 氯化亚砜 、 甲基溴化镁 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 反应 6.5h， 生成 ethyl 2,4,6-trichloronicotinoylacetate
  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

• Compounds, processes for the preparation thereof and anti-tumor agents
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US05817669A1

  公开（公告）日：1998-10-06

  This invention relates to pyridone-carboxylic acid derivatives of the following formula or salts thereof: ##STR1## wherein R.sub.1 is a hydrogen atom, a halogen atom, etc., R.sub.2 is a carboxyl group etc., R.sub.3 is a hydrogen atom etc., A is a nitrogen atom or CH, m is 1 or 2, and Y is an eliminable group or a group having the following formula: ##STR2## wherein R.sub.4 is a hydrogen atom or a lower alkyl group, Z is a hydrogen atom, a lower alkyl group, etc., R.sub.5 is a hydrogen atom, a lower alkyl group, etc., n is 0 or 1, and p is 1, 2, 3 or 4 and to processes for the preparation of these compounds, and further to anti-tumor agents which contain the above compounds as effective ingredients.

  本发明涉及具有以下通式的吡啶酮羧酸衍生物或其盐：##STR1##其中R1为氢原子、卤素原子等，R2为羧基等，R3为氢原子等，A为氮原子或CH，m为1或2，Y为可消除基团或具有以下通式的基团：##STR2##其中R4为氢原子或低级烷基，Z为氢原子、低级烷基等，R5为氢原子、低级烷基等，n为0或1，p为1、2、3或4，以及制备这些化合物的方法，并且进一步涉及含有上述化合物作为有效成分的抗肿瘤药物。
• NOVEL COMPOUND, PROCESS FOR PRODUCING THE SAME, AND ANTITUMOR AGENT
  申请人：DAINIPPON PHARMACEUTICAL CO., LTD.

  公开号：EP0787726B1

  公开（公告）日：2001-11-28
• US5817669A
  申请人：——

  公开号：US5817669A

  公开（公告）日：1998-10-06
• 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.