title: Design, synthesis, and structure-activity relationships of tetrahydroquinoline-based farnesyltransferase inhibitors.
abstract: Tetrahydroquinoline-based small molecule inhibitors of farnesyltransferase (FT) have been identified. Lead compounds were shown to have nanomolar to sub-nanomolar activity in biochemical assays with excellent potency in a Ras-mutated cellular reversion assay. BMS-316810 (9e), a 0.7 nM FT inhibitor, was orally-active in a nude mouse tumor allograft efficacy study.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, United States. louis.lombardo@bms.com
authors.forename: Louis J
authors.initials: LJ
authors.lastname: Lombardo
authors.forename: Amy
authors.initials: A
authors.lastname: Camuso
authors.forename: John
authors.initials: J
authors.lastname: Clark
authors.forename: Krista
authors.initials: K
authors.lastname: Fager
authors.forename: Johnni
authors.initials: J
authors.lastname: Gullo-Brown
authors.forename: John T
authors.initials: JT
authors.lastname: Hunt
authors.forename: Ivan
authors.initials: I
authors.lastname: Inigo
authors.forename: David
authors.initials: D
authors.lastname: Kan
authors.forename: Barry
authors.initials: B
authors.lastname: Koplowitz
authors.forename: Francis
authors.initials: F
authors.lastname: Lee
authors.forename: Kelly
authors.initials: K
authors.lastname: McGlinchey
authors.forename: Ligang
authors.initials: L
authors.lastname: Qian
authors.forename: Carolyn
authors.initials: C
authors.lastname: Ricca
authors.forename: George
authors.initials: G
authors.lastname: Rovnyak
authors.forename: Sarah
authors.initials: S
authors.lastname: Traeger
authors.forename: John
authors.initials: J
authors.lastname: Tokarski
authors.forename: David K
authors.initials: DK
authors.lastname: Williams
authors.forename: Laurence I
authors.initials: LI
authors.lastname: Wu
authors.forename: Yufen
authors.initials: Y
authors.lastname: Zhao
authors.forename: Veeraswamy
authors.initials: V
authors.lastname: Manne
authors.forename: Rajeev S
authors.initials: RS
authors.lastname: Bhide
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051231:Farnesyltranstransferase; D051379:Mice; D008819:Mice, Nude; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011804:Quinolines; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase