title: Discovery of potent imidazole and cyanophenyl containing farnesyltransferase inhibitors with improved oral bioavailability.
abstract: A pyridyl moiety was introduced into a previously developed series of farnesyltransferase inhibitors containing imidazole and cyanophenyl (such as 4), resulting in potent inhibitors with improved pharmacokinetics.
authors.affiliation: R47B, AP10, Global Pharmaceutical R&D, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6101, USA. yunsong.tong@abbott.com
authors.forename: Yunsong
authors.initials: Y
authors.lastname: Tong
authors.forename: Nan-Horng
authors.initials: NH
authors.lastname: Lin
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.forename: Lisa
authors.initials: L
authors.lastname: Hasvold
authors.forename: Weibo
authors.initials: W
authors.lastname: Wang
authors.forename: Nicholas
authors.initials: N
authors.lastname: Leonard
authors.forename: Tongmei
authors.initials: T
authors.lastname: Li
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Jerry
authors.initials: J
authors.lastname: Cohen
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Gu
authors.forename: Haiying
authors.initials: H
authors.lastname: Zhang
authors.forename: Vincent
authors.initials: V
authors.lastname: Stoll
authors.forename: Joy
authors.initials: J
authors.lastname: Bauch
authors.forename: Kennan
authors.initials: K
authors.lastname: Marsh
authors.forename: Saul H
authors.initials: SH
authors.lastname: Rosenberg
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
mesh_terms: D000284:Administration, Oral; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001682:Biological Availability; D018360:Crystallography, X-Ray; D004285:Dogs; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051231:Farnesyltranstransferase; D000882:Haplorhini; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D009570:Nitriles; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase