Easily hydrolyzable, water-soluble derivatives of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazoline-4-one, a novel antiviral compound.
The preparation of a series of indole N-acyl and N-carbamic esters of (+/-)-alpha-5-[1-(indol-3-yl)ethyl]-2-methylamino-delta2-thiazolin-4-one (1) is reported. These derivatives were synthesized as potential water-soluble precursors of the antiviral thiazolinone 1, for evaluation by intranasal administration against influenza and other respiratory infections caused by viruses. Salts of the basic carbamic esters (16--19) possess the required water solubility, undergo rapid hydrolysis and decarboxylation at pH values greater than 6, and have high activity against influenza A2 and Coxsackie B1 viruses in vitro. In influenza A2 infected ferrets a representative ester (16) reduced the severity and duration of disease symptoms and reduced nasal wash virus titres but caused local irritancy.
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis*; D029822:Enterovirus B, Human / Q000187:drug effects; D005289:Ferrets; D006868:Hydrolysis; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D009980:Influenza A virus / Q000187:drug effects; D009976:Orthomyxoviridae Infections / Q000188:drug therapy; D012995:Solubility; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D007211:Indoles; D013844:Thiazoles