3-ethyl-5-(3-methyl-3H-benzooxazol-2-ylidene)-2-thioxo-thiazolidin-4-one | 25149-96-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑啉
• 英文名称: 3-ethyl-5-(3-methyl-3H-benzooxazol-2-ylidene)-2-thioxo-thiazolidin-4-one
• 英文别名: (5E)-3-ethyl-5-(3-methyl-1,3-benzoxazol-2-ylidene)-2-sulfanylidene-1,3-thiazolidin-4-one
• CAS: 25149-96-6
• 化学式: C₁₃H₁₂N₂O₂S₂
• 分子量: 292.382
• InChiKey: DGTUEKDZGLCVNX-ZRDIBKRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  90.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-ethyl-5-(3-methyl-3H-benzooxazol-2-ylidene)-2-thioxo-thiazolidin-4-one 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.0h， 生成 Toluene-4-sulfonate1-ethyl-2-[3-ethyl-5-[3-methyl-3H-benzooxazol-(2E)-ylidene]-4-oxo-thiazolidin-(2Z)-ylidenemethyl]-pyridinium;
  参考文献：
  名称：

  Structure−Activity of Novel Rhodacyanine Dyes as Antitumor Agents

  摘要：

  We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized into class I and II depending on the methine length, were synthesized and evaluated as a novel antitumor agent. Attention was particularly focused on the structure-activity study of two heteroaromatic rings. In class I, where the A rings were conjugated to rhodanine via two methine groups, compounds 1, 20, 23, and 24 were found to be efficacious in tumor-bearing nude mice model study, but they did not have the chemical properties (stability, solubility) suitable for clinical use. In contrast, in class II, where the A rings were directly conjugated to rhodanine, compounds 13 and 25, which possessed a benzothiazole moiety for the A ring, exhibited the favarable biological and chemical properties. Therefore, we decided to have a benzothiazole moiety as the A ring and introduce various heterocyclic groups for the B ring. As a result, the pyridinium ring was selected as the optimal moiety for the B ring (compound 13). Further, the variation of counteranion had a profound effect on solubility in water without influence on antitumor activity. Chloride anion was selected as the favorable anion with respect to synthetic method as well as solubilty in water. Our study finally led us to the identification of compound 3 (MKT 077, 1-ethyl-2-[[3-ethyl-5-(methylbenzothiazolin-2-ylidene)-4-oxothiazolidin-2-ylidene]methyl]pyridinium chloride) as the candidate for clinical trials and is currently subjected to further investigation as a potent antitumor agent in phase I clinical trial for the treatment of solid tumors.

  DOI：

  10.1021/jm970590k
• 作为产物：
  描述：

  3-乙基-2-硫代-4-噻唑烷二酮 、 2-<(N-Methyl-1,2-dihydro-chinolyliden-(2)-methyl>-N-methyl-benzoxazolium-iodid 在 吡啶 作用下， 生成 3-ethyl-5-(3-methyl-3H-benzooxazol-2-ylidene)-2-thioxo-thiazolidin-4-one
  参考文献：
  名称：

  Metzger,J. et al., Bulletin de la Societe Chimique de France, 1969, p. 1284 - 1293

  摘要：

  DOI：

文献信息

• Metzger,J. et al., Bulletin de la Societe Chimique de France, 1969, p. 1284 - 1293
  作者：Metzger,J. et al.

  DOI：——

  日期：——
• Structure−Activity of Novel Rhodacyanine Dyes as Antitumor Agents
  作者：Masayuki Kawakami、Keizo Koya、Toshinao Ukai、Noriaki Tatsuta、Akihiko Ikegawa、Keizo Ogawa、Tadao Shishido、Lan Bo Chen

  DOI：10.1021/jm970590k

  日期：1998.1.1

  We have previously reported that rhodacyanine dyes, such as 1 and 2, exhibited a potent inhibitory effect on the growth of several tumor cells and that 4-oxothiazolidine (rhodanine) was an essential moiety for antitumor activity. On the basis of our foregoing work, two types of rhodacyanine dyes, which categorized into class I and II depending on the methine length, were synthesized and evaluated as a novel antitumor agent. Attention was particularly focused on the structure-activity study of two heteroaromatic rings. In class I, where the A rings were conjugated to rhodanine via two methine groups, compounds 1, 20, 23, and 24 were found to be efficacious in tumor-bearing nude mice model study, but they did not have the chemical properties (stability, solubility) suitable for clinical use. In contrast, in class II, where the A rings were directly conjugated to rhodanine, compounds 13 and 25, which possessed a benzothiazole moiety for the A ring, exhibited the favarable biological and chemical properties. Therefore, we decided to have a benzothiazole moiety as the A ring and introduce various heterocyclic groups for the B ring. As a result, the pyridinium ring was selected as the optimal moiety for the B ring (compound 13). Further, the variation of counteranion had a profound effect on solubility in water without influence on antitumor activity. Chloride anion was selected as the favorable anion with respect to synthetic method as well as solubilty in water. Our study finally led us to the identification of compound 3 (MKT 077, 1-ethyl-2-[[3-ethyl-5-(methylbenzothiazolin-2-ylidene)-4-oxothiazolidin-2-ylidene]methyl]pyridinium chloride) as the candidate for clinical trials and is currently subjected to further investigation as a potent antitumor agent in phase I clinical trial for the treatment of solid tumors.