β-Lapachone: Synthesis of Derivatives and Activities in Tumor Models

Article abstract of DOI:10.1021/jm00374a010

In order to find a 3,4-dihydro-2H-naphtho<1,2-b>pyran-5,6-dione more potent than the naturally occurring 2,2-dimethyl derivative <β-lapachone (10a)>, we synthesized a series of analogous compounds with modifications at position 2 of the pyran ring or at positions 8 and 9 of the benzene ring.Of the compounds tested in vitro for inhibition of RNA-dependent DNA polymerase and in mice infected with Rauscher leukemia, all retained good enzyme activity.Inhibition of the reverse transcriptase activity of the 2,2-substituted derivatives 10b-e was as strong as 10a.However, only the 2-methyl-2-phenyl derivative 10e proved to be about as potent as 2,2-dimethyl reference compound 10a in prolonging the mean survival time of mice with Rauscher leukemia virus induced leukemia.