3747-06-6Relevant articles and documents
Synthesis of three classes of rhodacyanine dyes and evaluation of their in vitro and in vivo antimalarial activity
Pudhom, Khanitha,Kasai, Kazuki,Terauchi, Hiroki,Inoue, Hiroshi,Kaiser, Marcel,Brun, Reto,Ihara, Masataka,Takasu, Kiyosei
, p. 8550 - 8563 (2006)
Selected members of three classes of rhodacyanine dyes, [0, 0]-, [1, 0]-, and [0, 0, 0]-rhodacyanines, were synthesized and their in vitro antimalarial activities against Plasmodium falciparum K1 (chloroquine-resistant strain) as well as their in vivo activities against P. berghei in mice were determined. The novel [0, 0, 0]-rhodacynines, 3e and 3h, possessing a benzothiazole moiety, were shown to have highly promising antimalarial activities in vivo. Moreover, the [0, 0, 0]-rhodacyanines were found to be orally bioavailable.
Structure-activity of novel rhodacyanine dyes as antitumor agents
Kawakami, Masayuki,Koya, Keizo,Tatsuta, Toshinao,Noriaki, Ukai T.,Ikegawa, Akihiko,Ogawa, Keizo,Shishido, Tadao,Chen, Lan Bo
, p. 130 - 142 (2007/10/03)
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 favorable 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 solubility 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]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.
A 2-methylthio-3,5-diaryl-1,3,4-thiadiazolium cation; its reactions, and further exploration of the chemistry of 2-alkyl-3,5-diaryl-1,3,4-thiadiazolium cations
Mastalerz, Harold,Mohammad, Taj,Gibson, Martin S.
, p. 2713 - 2716 (2007/10/02)
Activation of a representative 3,5-diaryl-1,3,4-thiadiazole-2-thione by thione S-methylation gives a cation that is readily susceptible to nucleophilic substitution.Reactions with diethyl malonate, ethyl acetoacetate, acetylacetone, cyclopentan-1,3-dione, or 3-ethylrhodanine under basic conditions led to β,β-disubstituted methine bases and (or) β-substituted methine bases in cases where deacetylation occurs under the reaction conditions.This cation and the 2-alkyl-3,5-diaryl-1,3,4-thiadiazolium cation are convenient sources of a series of neutral and cationic dyes containing the 1,3,4-thiadiazole ring system.
