SYNTHESIS AND ANTIVIRAL ACTIVITY OF 3 PYRAZOLE ANALOGS OF DISTAMYCIN-A

The synthesis of three new monopyrazole analogues of the antiviral com pound distamycin A is reported. Suitably protected 4-amino-1-methylpyr role-2-carboxylic acid and 3-amino-1-methylpyrazole-5-carboxylic acid derivatives were chosen as starting materials. The construction of the trimeric polyamide framework was accomplished by assembly of the mono meric precursors under condensing conditions by analogy with our previ ous methodology, although with significant improvements in some pivota l steps. After chromatographic purification and spectroscopic characte risation, the analogues were assayed for antiviral activity. Compounds 7a-c inhibited vaccinia virus at a concentration similar to or lower than distamycin A and the related antibiotic netropsin. Analogues 7b a nd 7c exhibited an antiviral effect comparable to those of distamycin A and netropsin against HSV-1 and HSV-2, whereas their antiviral activ ity against several other viruses including HIV-1 and HIV-2 was somewh at lower. The cellular toxicity of 7a-c toward different host cell typ es proved to be of similar magnitude or lower than those of distamycin A and netropsin.