A series of novel N-cyanoguanidine tricyclic farnesyl protein transferase (FPT) inhibitors was prepared. Replacement of a piperidine amide-group with a N-cyanoguanidine functionality increased FPT activity. X-ray crystal structure determination of 42 complexed with FPT revealed differences in the interactions of the amide and N-cyanoguanidine groups with the protein.
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