Synthesis and antiallergic activity of dimethyl-2-(phenylcarbamoyl)ethylsulfonium p-toluenesulfonate derivatives.
The derivatives of dimethyl-2-(phenylcarbamoyl)ethylsulfonium p-toluenesulfonates were synthesized and evaluated for antiallergic activity. The 2,3-dihydroxyethoxy group was introduced to the phenyl ring from the standpoint of lipophilicity and electronic effects of substituent. The IgE-induced rat passive cutaneous anaphylaxis (PCA) was inhibited by oral administration of several substituted 2-[(4-propoxyphenyl)carbamoyl]ethyldimethylsulfonium p-toluenesulfonate derivatives. Among them (+/-)-2-[N-[4-(3-ethoxy-2-hydroxypropoxy)phenyl]carbamoyl]ethyldimeth ylsulfonium p-toluenesulfonate (1a, IPD-1151T) was found to possess considerable activity in the PCA test, and it was launched as Suplatast tosilate in Japan.
Tada
Y
Y
Hanno Research Center, Taiho Pharmaceutical Company, Ltd., 1-27 Misugidai, Hanno, Saitama 357, Japan.
Yamawaki
I
I
Ueda
S
S
Matsumoto
H
H
Matsuura
N
N
Yasumoto
M
M
Koda
A
A
Hori
M
M
D000818:Animals; D018926:Anti-Allergic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001190:Arylsulfonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D007073:Immunoglobulin E / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects / Q000276:immunology; D051381:Rats; D013329:Structure-Activity Relationship; D013452:Sulfonium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D018926:Anti-Allergic Agents; D001190:Arylsulfonates; D013452:Sulfonium Compounds; D007073:Immunoglobulin E; C073028:suplatast tosilate