title: Aryl tetrahydropyridine inhibitors of farnesyltransferase: glycine, phenylalanine and histidine derivatives.
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 a series of aryl tetrahydropyridines that incorporate substituted glycine, phenylalanine and histidine residues. 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*; D001682:Biological Availability; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D011905:Genes, ras / Q000187:drug effects; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006639:Histidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011725:Pyridines; D010649:Phenylalanine; D006639:Histidine; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; D005998:Glycine