Synthesis of conformationally constrained 5,6,7,8-tetrahydroimidazo[1,5-a]pyridine inhibitors of farnesyltransferase

[GRAPHICS] Synthesis of the 8-amino-5,6,7,8-tetrahydroimidazo[1,5 a]pyridine ring syst em was accomplished by intramolecular cyclization of an iminium ion, derive d from condensation of an amine and a substituted gamma-(1-imidazolyl)butyr aldehyde. The reaction was used to produce conformationally restricted farn esyltransferase inhibitor analogues which exhibit improved in vivo metaboli c stability.