Synthesis and use of .beta.-lapachone analogs

Details Synthesis and use of .beta.-lapachone analogs Synthesis and use of .beta.-lapachone analogs

1995-04-25

1998-06-09

Richter, Johann

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

549391, 549393, 549395, C07D31180

Patent

active

057636257

ABSTRACT:
3-Substituted-.beta.-lapachone analogs and their use either alone or to augment chemotherapy or radiotherapy to induce programmed neoplastic cell death without exhibiting toxicity to surrounding normal cells are disclosed. In particular, 3-allyl-.beta.-lapachones, 3-alkyl-.beta.-lapachones and 3-halo-.beta.-lapachones were found to be Topoisomerase (Topo I) inhibitors. When these analogs are used alone there is a reversible single-strand break in the DNA of neoplastic cells causing apoptosis and cell death in some cells. However, when these analogs are combined with chemotherapy or X-irradiation, an irreversible Topo I-mediated break is achieved. A new and more efficient chemical synthesis of the compounds is also disclosed.

REFERENCES:
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