Inhibitors Of Farnesyl Protein Transferase. Synthesis And Biological Activity Of Amide And Cyanoguanidine Derivatives Containing A 5,11-Dihydro[1]Benzthiepin, Benzoxepin, And Benzazepin [4,3-B]Pyridine Ring System.

Bioisosteric replacement of the C-6 carbon atom in piperidine I and piperazine II with S, O, and N heteroatoms is described. Amide and cyanoguanidine derivatives of these compounds were evaluated in vitro and found to be good inhibitors of farnesyl-protein transferase. An improved method of preparing the 5,11-dihydro-[1]-benzthiepin nucleus 6 was accomplished in high yield and with excellent regioselectivity using an AlCl3 melt protocol. (C) 1998 Elsevier Science Ltd. All rights reserved.