The specific aims of this proposal are to develop analogues and prodrugs of bis-acyloxymethyl-pyrroles and -pyrrolizines which will have improved stability and water-solubility compared to existing agents in this class; to study structure-activity requirements for compounds in this class; to develop new """"""""lead"""""""" structures based on polycyclic benz-fused pyrroles and on heterocyclic nuclei other than pyrroles; to examine the effects of selected agents in this class on tumor cell function in order to develop an understanding of the mechanism of action of these agents.
These specific aims relate to the long term goals of the project which are to develop clinically useful antineoplastic agents which show activity against a broad range of tumors and, in particular, against the more intractable tumors. These specific objectives also relate to the long term goals of developing more potent, less toxic antitumor agents in the new class of antitumor agents referred to as acylated vinylogous carbinolamines.
