Synthesis, antiviral (HSV-1) and antimycotic activities of ethyl or methyl 2,4-disubstituted 5-pyrimidinecarboxylates, 2,4-disubstituted 5-pyrimidinecarboxylic acids and 2,4-disubstituted pyrimidines.
The synthesis of ethyl or methyl 4-substituted or unsubstituted 2-methylthio-5-pyrimidinecarboxylates 3 a-i and 8 o mainly by reaction of ethyl or methyl 2-dimethylaminomethylene-3-oxoalkanoates with 2-methylisothiourea is described. Also some ethyl 2-substituted (NH2, CH3, C6H5) 4-trifluoromethyl-5-pyrimidinecarboxylates were prepared. Some of the above esters were hydrolyzed to the relative carboxylic acids, which were decarboxylated to the corresponding 2,4-disubstituted pyrimidines. Esters 3 a-i and 8 o were tested for their toxicity on Vero cultured cells and for their inhibitory activity against herpes simplex virus type 1 (HSV-1) infectivity in a short-term plaque assay. At non toxic concentrations, each ester was found to be active, the most interesting compound being 3 h, which achieved a 80.9% inhibition of HSV-1 infectivity at 12 micrograms/ml. Moreover, esters 3 f, 8 l and acid 9 o were active against some fungal strains.
Istituto di Scienze Farmaceutiche dell'Università, Genova, Italy.
L
L
Sansebastiano
L
L
Mosti
G
G
Menozzi
P
P
Schenone
O
O
Muratore
A
A
Petta
E
E
Debbia
A P
AP
Schito
G C
GC
Schito
D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects*; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D014709:Vero Cells; D010948:Viral Plaque Assay
D000935:Antifungal Agents; D000998:Antiviral Agents; D011743:Pyrimidines