3-ethyl-5-(1-methyl-1H-pyridin-2-ylidene)-2-methylsulfanyl-4-oxo-4,5-dihydro-3-thiazolium p-toluenesulfonate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-ethyl-5-(1-methyl-1H-pyridin-2-ylidene)-2-methylsulfanyl-4-oxo-4,5-dihydro-3-thiazolium p-toluenesulfonate
• 英文别名: (5Z)-3-ethyl-5-(1-methylpyridin-2-ylidene)-2-methylsulfanyl-1,3-thiazol-3-ium-4-one;4-methylbenzenesulfonate
• 化学式: C₇H₇O₃S*C₁₂H₁₅N₂OS₂
• 分子量: 438.593
• InChiKey: FGGSUYRZQOLTNK-KVVVOXFISA-M

计算性质

• 辛醇/水分配系数(LogP)：
  3.14
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  140
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-乙基-2-甲基苯并唑对甲基苯磺酸酯 、 3-ethyl-5-(1-methyl-1H-pyridin-2-ylidene)-2-methylsulfanyl-4-oxo-4,5-dihydro-3-thiazolium p-toluenesulfonate 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 (2Z,5Z)-3-ethyl-2-[(3-ethyl-1,3-benzothiazol-3-ium-2-yl)methylidene]-5-(1-methylpyridin-2-ylidene)-1,3-thiazolidin-4-one;4-methylbenzenesulfonate
  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 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 8.0h， 生成 3-ethyl-5-(1-methyl-1H-pyridin-2-ylidene)-2-methylsulfanyl-4-oxo-4,5-dihydro-3-thiazolium p-toluenesulfonate
  参考文献：
  名称：

  WO2006/137258

  摘要：

  公开号：

文献信息

• PHARMACEUTICAL COMPOSITION COMPRISING AZARHODACYANINE COMPOUND AS ACTIVE INGREDIENT
  申请人：Japan Science and Technology Agency

  公开号：EP1894920A1

  公开（公告）日：2008-03-05

  The object of the invention is to provide pharmaceutical composition that can be used as a therapeutic and/or prophylactic agent. Particularly, the pharmaceutical composition of the invention has significant therapeutic effect and survival benefit for the disease caused by parasitic protozoa, and selective toxicity against the causative protozoa. The pharmaceutical composition comprises a compound represented by general formula (1). Particularly, the invention relates to a composition that is an effective therapeutic/prophylactic agent for malaria, leishmania, African sleeping sickness, Chagas disease, toxoplasmosis lymphatic filariasis, babesiosis, and coccidiosis, and a novel compound contained therein.

  本发明的目的是提供可用作治疗和/或预防剂的药物组合物。特别是，本发明的药物组合物对寄生原虫引起的疾病有显著的治疗效果和生存益处，并对致病原虫有选择性毒性。该药物组合物包含通式（1）所代表的化合物。特别是，本发明涉及一种对疟疾、利什曼病、非洲昏睡病、南美锥虫病、弓形虫病淋巴丝虫病、巴贝丝虫病和球虫病具有有效治疗/预防作用的组合物，以及其中所含的一种新型化合物。
• Rhodacyanine Dyes as Antimalarials. 1. Preliminary Evaluation of Their Activity and Toxicity
  作者：Kiyosei Takasu、Hiroshi Inoue、Hye-Sook Kim、Makoto Suzuki、Tadao Shishido、Yusuke Wataya、Masataka Ihara

  DOI：10.1021/jm0155704

  日期：2002.2.1

  The rhodacyanine dye MKT-077 (1), a potent antitumor agent, was found to possess strong in vitro activity against Plasmodium falciparum and a low cytotoxicity. Several new rhodacyanine dyes related to 1, containing a variety of linked heterocyclic moieties, were synthesized, and their antimalarial potencies were evaluated. The synthetic rhodacyanines were found to have EC50 values against P. falciparum in vitro in the range of 4-300 nM. Several compounds in this series have remarkable selective toxicity profiles (> 100).
• Synthesis and Antimalarial Efficacy of Aza-Fused Rhodacyanines in Vitro and in the <i>P. berghei </i>Mouse Model
  作者：Kiyosei Takasu、Khanitha Pudhom、Marcel Kaiser、Reto Brun、Masataka Ihara

  DOI：10.1021/jm0606241

  日期：2006.7.1

  Several aza-fused rhodacyanines were synthesized and assessed for their in vitro and in vivo antimalarial activities against Plasmodium falciparum K1 and P. berghei. All synthetic compounds showed strong selective antimalarial in vitro activity. Class II azarhodacyanines, 3, consisting of four heterocyclic units, were found to display good parasitemia suppression and low acute toxicity in vivo. Among them, 3c appeared to be the most effective at a dose of 20-25 mg kg-1 day-1 (ip).
• 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.
• WO2006/137258
  申请人：——

  公开号：——

  公开（公告）日：——