title: Benzimidazolones and indoles as non-thiol farnesyltransferase inhibitors based on tipifarnib scaffold: synthesis and activity.
abstract: A series of analogs of tipifarnib (1) has been synthesized as inhibitors of FTase by substituting the benzimidazolones and indoles for the 2-quinolone of tipifarnib. The novel benzimidazolones are potent and selective FTase inhibitors (FTIs) with IC(50) values of the best compounds close to that of tipifarnib. The current series demonstrate good cellular activity as measured in their inhibiting the Ras processing in NIH-3T3 cells, with compounds 2c and 2f displaying EC(50) values of 18 and 22nM, respectively.
authors.affiliation: Cancer Research, GPRD, Abbott Laboratories, Abbott Park, IL 60064-6101, USA. qun.li@abbott.com
authors.forename: Qun
authors.initials: Q
authors.lastname: Li
authors.forename: Tongmei
authors.initials: T
authors.lastname: Li
authors.forename: Keith W
authors.initials: KW
authors.lastname: Woods
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Gu
authors.forename: Jerry
authors.initials: J
authors.lastname: Cohen
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Stoll
authors.forename: Tomas
authors.initials: T
authors.lastname: Galicia
authors.forename: Charles
authors.initials: C
authors.lastname: Hutchins
authors.forename: David
authors.initials: D
authors.lastname: Frost
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*; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D015363:Quinolones / Q000737:chemistry*
chemical_list: D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D007211:Indoles; D015363:Quinolones; C014353:benzimidazolone; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; C402769:tipifarnib