Synthesis of new 3,4,5-trisubstituted isothiazoles as effective inhibitory agents of enteroviruses.
The synthesis and evaluation of 3,4,5-trisubstituted isothiazoles as antiviral agents led to the discovery of several compounds effective in vitro against enteroviruses polio 1 and ECHO 9. Structure-activity relationship studies revealed that a short thioalkyl chain in the 3-position and a methyl ester group in the 4-position are the structural components that, to a large extent, contribute to the positive biological profile in terms of both selectivity and low cytotoxicity. Under one-step growth conditions, methyl 3-methylthio-5-phenyl-4-isothiazolecarboxilate caused the greatest activity if added within 1 h after poliovirus adsorption. These data suggest interference with early events of viral replication.
Cutrì
C C
CC
Dipartimento di Scienze Farmaceutiche, Università di Catania, Italy.
Garozzo
A
A
Siracusa
M A
MA
Sarvà
M C
MC
Castro
A
A
Geremia
E
E
Pinizzotto
M R
MR
Guerrera
F
F
D000998:Antiviral Agents / Q000494:pharmacology; D004770:Enterovirus / Q000187:drug effects*; D029822:Enterovirus B, Human / Q000187:drug effects; D008956:Models, Chemical; D017955:Poliovirus / Q000187:drug effects; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013997:Time Factors
D000998:Antiviral Agents; D013844:Thiazoles