A Correlation between Physicochemical Properties and Acute Toxicity of Sulfonium p-Toluenesulfonates as the Lead Compound of Suplatast Tosilate

• Published in: Chem-Bio Informatics Journal Vol. 1; no. 2; pp. 84 - 93
• Main Authors: Tada, Yukio, Yamawaki, Ichiro, Ueda, Shuichi, Matsumoto, Hiroshi, Matsuura, Naosuke, Yasumoto, Mitsugi, Koda, Akihide, Hori, Mikio
• Format: Journal Article
• Language: English
• Published: Tokyo Chem-Bio Informatics Society 2001; Japan Science and Technology Agency
• Subjects: H-D Exchange Reaction; Methyl transfer Reaction; SAR; Sulfonium p-toluenesulfonate; Suplatast Tosilate
• ISSN: 1347-6297; 1347-0442
• DOI: 10.1273/cbij.1.84

To elucidate the correlation between the physicochemical properties and biological activity of sulfonium compound, the kinetics of H-D exchange and methyl transfer reactions were investigated as its remarkable properties. There was a good correlation between acute toxicity (LD 50 ) and rate constants of H-D exchange or methyl transfer reactions. The control of toxicity is very important in the development of a new drug. The high reactivity of methyl group was not desirable in acute toxicity, therefore, sulfonium p-toluenesulfonates that do not contain unsaturated carbon as a substituent of sulfur were desirable for reducing toxicity. Furthermore it was revealed that OH and COOH groups reduced acute toxicity substantially. The information on toxicity reduction was used in the design of Suplatast Tosilate