title: Potent inhibitors of farnesyltransferase and geranylgeranyltransferase-I.
abstract: Compound 1 has been shown to be a dual prenylation inhibitor with FPTase (IC50=2 nM) and GGPTase-I (IC50=95 nM). Analogues of 1, which replaced the cyanophenyl group with various biaryls, led to the discovery of highly potent dual FPTase/GGPTase-I inhibitors. 4-trifluoromethylphenyl, trifluoropentynyl, and trifluoropentyl were identified as good p-cyano replacements.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. diem_nguyen@merck.com
authors.forename: Diem N
authors.initials: DN
authors.lastname: Nguyen
authors.forename: Craig A
authors.initials: CA
authors.lastname: Stump
authors.forename: Eileen S
authors.initials: ES
authors.lastname: Walsh
authors.forename: Christine
authors.initials: C
authors.lastname: Fernandes
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Davide
authors.forename: Michelle
authors.initials: M
authors.lastname: Ellis-Hutchings
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Robinson
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Williams
authors.forename: Robert B
authors.initials: RB
authors.lastname: Lobell
authors.forename: Hans E
authors.initials: HE
authors.lastname: Huber
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Buser
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; C064911:p21(ras) farnesyl-protein transferase