3-Cyclic amine derivatives of rifamycin: strong inhibitors of the DNA polymerase activity of RNA tumor viruses

Abstract

Derivatives of rifamycin-SV with substituted cyclic-amine side chains in position 3 of the ansa ring are strong inhibitors of RNA-directed DNA and DNA-directed DNA polymerase activity of RNA tumor viruses of murine, feline, and avian origin. Among 37 3-amine derivatives of rifamycin-SV that were tested, 29 3-cyclic amine derivatives were good inhibitors of the viral polymerases. Especially active were 3-piperidyl derivatives of rifamycin-SV with cyclohexyl and cyclohexylalkyl substituents. Derivatives that were effective against the viral polymerase also blocked cell transformation by the murine sarcoma virus. A DNA-directed DNA polymerase preparation from human KB cells was less sensitive to inhibition by these derivatives than the virion polymerase.