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New Isothiazole Derivatives: Synthesis, Reactivity, Physicochemical Properties and Pharmacological Activity
Author(s) -
Regiec Andrzej,
Machoń Zdzisław,
Miedzybrodzki Ryszard,
Szymaniec Stanisław
Publication year - 2006
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200500040
Subject(s) - isothiazole , chemistry , amide , biological activity , stereochemistry , acylation , chemical synthesis , structure–activity relationship , medicinal chemistry , organic chemistry , in vitro , biochemistry , catalysis
The synthesis and biological investigation of the series of amide and ester derivatives 10–20 of 5‐(4‐chlorobenzoyl)amino‐3‐methyl‐4‐isothiazolecarboxylic acid 5 are presented. Because the amide series of 5‐benzoylamino‐3‐methyl‐4‐isothiazolecarboxylic acid 2 has been studied extensively and from this series denotivir (vratizolin) 4 [1, 2] became the antiviral drug. The influence of exchanging the N‐ benzoyl for a N‐ (4‐chlorobenzoyl) group at position 5 of the isothiazole ring on the pharmacological activity of 5‐benzoylamino‐3‐methyl‐4‐isothiazolecarboxylic acid 2 derivatives is dealt with here. The effect of structure modifications in the carboxylic group of the 5‐(4‐chlorobenzoyl)amino‐3‐methyl‐4‐isothiazolecarboxylic acid 5 series of derivatives on their biological activity is discussed. Some of the tested 5‐(4‐chlorobenzoyl)amino‐3‐methyl‐4‐isothiazolecarboxylamides revealed significant anti‐inflammatory activity in carrageenan induced edema and air‐pouch inflammation tests. Physicochemical properties of 6‐(4‐chlorophenyl)‐3‐methylisothiazolo[5,4‐ d ]‐4 H ‐1,3‐oxazin‐4‐one 6 are described. Its use in the synthesis of isothiazole derivatives and its reactivity are also presented.