Lead Generation of Anti-allergic Agent ; Suplatast Tosilate

Tada, Yukio; Yamawaki, Ichiro; Ueda, Shuichi; Matsumoto, Hiroshi; Matsuura, Naosuke; Yasumoto, M.; Koda, Akihide; Hori, Mikio

doi:10.1273/cbij.1.51

Cited by 5 publications

(9 citation statements)

References 15 publications

(10 reference statements)

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“…Note that the sulfonium salts with a structure R-S þ Me 2 ,X À published in the literature have a chemical shift for the methyl groups between 2.7 and 3.4 ppm depending on the structure of R and the deuterated solvent used. [6,[11][12][13] To conclude, all these results support our interpretation of the synthesized polypentadienes NMR spectra. That is to say, the peaks observed at 3.11 and 3.27 ppm were due to methyl groups of the polymer sulfonium end (-S þ Me 2 ,X À ).…”

Section: H Nmrsupporting

confidence: 88%

Demonstration of the Existence of Long‐Lived Species in the Cationic Polymerization of 1,3‐Pentadiene Initiated by Aluminium Trichloride in Non Polar Solvent

Bennevault‐Celton¹,

Delfour²,

Cheradame³

2004

Macro Chemistry & Physics

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Summary: A kinetic study of the polymerization of a mixture of 1,3‐pentadiene isomers initiated by AlCl3 was carried out in pentane at −10 and 20 °C. A second apparent monomer order was found mainly at room temperature and was explained by a complexation of propagating active centers by the polymer, the true monomer order being first. This apparent order did not result from the presence of the two isomers in the monomer mixture. Kinetic simulations confirmed this interpretation and pointed out the fact that the interaction between the polymer and the active centers was stronger at −10 °C, thus limiting the polymer conversion at this temperature. The novelty of these findings lies in the fact that the inactive complexed centers can be activated by reaction with the monomer, providing active species when necessary. The existence of active centers even after a long reaction time at room temperature, and the reactivation of the complexed centers, was evidenced by incremental monomer addition and by the formation of sulfonium ions after quenching the polymerization by an excess of dimethyl sulfide. The latter were characterized by 1H NMR spectroscopy.

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Section: H Nmrsupporting

confidence: 88%

Demonstration of the Existence of Long‐Lived Species in the Cationic Polymerization of 1,3‐Pentadiene Initiated by Aluminium Trichloride in Non Polar Solvent

Bennevault‐Celton¹,

Delfour²,

Cheradame³

2004

Macro Chemistry & Physics

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“…The dialkyl sulfides were easily methylated with methyl p-toluenesulfonate and gave sulfonium p-toluenesulfonates (1-5, 12) at room temperature [2], whereas the aryl and vinyl sulfides needed to be heated at 100 ˚C with methyl p-toluenesulfonate to obtain sulfonium p-toluenesulfonates (6-11, 13).…”

Section: Synthesis Of Sulfonium P-toluenesulfonatesmentioning

confidence: 99%

“…The H-D exchange rate constants (k obsd/HD ) are shown in Table 1. Methyl groups of sulfonium p-toluenesulfonates (6)(7)(8)(9)(10)(11)13), which have unsaturated carbon adjacent to positive sulfur, exchanged their protons about 13 times more rapidly than did other compounds (1)(2)(3)(4)(5)12). There were not any significant correlations between k obsd/H-D and immunological activity (HPFC).…”

Section: Kinetics Of the H-d Exchange Reactions And Biological Activimentioning

confidence: 99%

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

幸雄

一郎

修一

et al. 2001

CBIJ

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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.

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“…During the development of Suplatast Tosilate (IPD-1151T) (67) (Chart 1), which is a Th2 cytokine inhibitor and used as anti-allergic drug [3], we have reported some QSAR analysis by using only the calculated values as lipophilic parameter [5][6] [7][8] [9] [10], because the logK values of sulfonium compounds had been previously only rarely measured. We could comprehend the relative lipophilicity of sulfonium compounds in the developmental process (Chart1), but we did not determine a suitable logK value for the anti-allergic activity and toxicity.…”

Section: Introductionmentioning

confidence: 99%

Optimal Lipophilicity of Sulfonium <i>p</i>-Toluenesulfonate as Anti-allergic Drug

Tada

Yamawaki

Ueda

et al. 2012

CBIJ

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In the development of the anti-allergic drug Suplatast Tosilate (IPD-1151T) we have reported the QSAR analysis using only the calculated values, because the few logK values of sulfonium compounds had been measured till then. In this study, we measured the logK TLC value of sulfonium compounds by using octylsililated silicagel plate (Merck HPTLC RP-8 F 254S ). The logK TLC values of the optimized compounds 52 and 67 (Suplatast Tosilate) of dimethylsulfonium p-toluenesulfonates derivatives were 0.07 and 0.06, respectively. Therefore, it was found that the desirable logK TLC value of the sulfonium compound was approximately zero as the anti-allergic drug.

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Lead Generation of Anti-allergic Agent ; Suplatast Tosilate

Cited by 5 publications

References 15 publications

Demonstration of the Existence of Long‐Lived Species in the Cationic Polymerization of 1,3‐Pentadiene Initiated by Aluminium Trichloride in Non Polar Solvent

Demonstration of the Existence of Long‐Lived Species in the Cationic Polymerization of 1,3‐Pentadiene Initiated by Aluminium Trichloride in Non Polar Solvent

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

Optimal Lipophilicity of Sulfonium <i>p</i>-Toluenesulfonate as Anti-allergic Drug

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