title: Aryl tetrahydropyridine inhibitors of farnesyltransferase: bioavailable analogues with improved cellular potency.
abstract: Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clinical trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered bioavailable aryl tetrahydropyridines that are potent in cell culture. The design, synthesis, SAR and biological properties of these compounds will be discussed.
authors.affiliation: Pharmaceutical Discovery, R47B, Building AP-10, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. stephen.gwaltney@syrrx.com
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Gwaltney
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: O'Connor
authors.forename: Lissa T J
authors.initials: LT
authors.lastname: Nelson
authors.forename: Gerard M
authors.initials: GM
authors.lastname: Sullivan
authors.forename: Hovis
authors.initials: H
authors.lastname: Imade
authors.forename: Weibo
authors.initials: W
authors.lastname: Wang
authors.forename: Lisa
authors.initials: L
authors.lastname: Hasvold
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Jerome
authors.initials: J
authors.lastname: Cohen
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Gu
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Tahir
authors.forename: Joy
authors.initials: J
authors.lastname: Bauch
authors.forename: Kennan
authors.initials: K
authors.lastname: Marsh
authors.forename: Shi-Chung
authors.initials: SC
authors.lastname: Ng
authors.forename: David J
authors.initials: DJ
authors.lastname: Frost
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Steve
authors.initials: S
authors.lastname: Muchmore
authors.forename: Clarissa G
authors.initials: CG
authors.lastname: Jakob
authors.forename: Vincent
authors.initials: V
authors.lastname: Stoll
authors.forename: Charles
authors.initials: C
authors.lastname: Hutchins
authors.forename: Saul H
authors.initials: SH
authors.lastname: Rosenberg
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000478:Alkylation; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D006207:Half-Life; D008958:Models, Molecular; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011725:Pyridines; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase