title: 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.
abstract: 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.
authors.affiliation: Schering-Plough Research Institute, Department of Chemistry, Kenilworth, New Jersey 07033, USA.
authors.forename: R
authors.initials: R
authors.lastname: Wolin
authors.forename: M
authors.initials: M
authors.lastname: Connolly
authors.forename: J
authors.initials: J
authors.lastname: Kelly
authors.forename: J
authors.initials: J
authors.lastname: Weinstein
authors.forename: S
authors.initials: S
authors.lastname: Rosenblum
authors.forename: A
authors.initials: A
authors.lastname: Afonso
authors.forename: L
authors.initials: L
authors.lastname: James
authors.forename: P
authors.initials: P
authors.lastname: Kirschmeier
authors.forename: W R
authors.initials: WR
authors.lastname: Bishop
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000577:Amides / Q000737:chemistry*; D001552:Benzazepines / Q000737:chemistry; D001584:Benzoxepins / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006146:Guanidines / Q000737:chemistry*; D008956:Models, Chemical; D010879:Piperazines / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D017368:Protein Prenylation / Q000187:drug effects*; D011725:Pyridines / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D001552:Benzazepines; D001584:Benzoxepins; D004791:Enzyme Inhibitors; D006146:Guanidines; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase; C004711:dicyandiamido