The design, synthesis, and evaluation of functional analogs of the potent antitumor antibiotic (+)-CC-1065 are detailed. A primary objective of the studies is the definition of the structural origin of the agents DNA alkylation selectivity. Concurrent with these efforts, the evaluation of analogs bearing deep seated structural changes continue to help define the relationship between their DNA alkylation properties and biological properties, provide key partial structures and fundamental new agents for evaluation, and have resulted in the preparation of a class of potentially useful antitumor agents. These studies will be fully developed in the current grant period.
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