title: New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis.
abstract: A new synthetic pathway was devised to reach tetrasubstituted 3-arylthiophene 2-carboxylic acids in a three-step solid-phase synthesis. This very efficient methodology provided more than 20 new compounds that were evaluated for their ability to inhibit protein farnesyltransferase from different species as well as Trypanosoma brucei and Plasmodium falciparum proliferation.
authors.affiliation: Institut de Chimie des Substances Naturelles, CNRS, Centre de Recherche de Gif, Gif sur Yvette, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lethu
authors.forename: Damien
authors.initials: D
authors.lastname: Bosc
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mouray
authors.forename: Philippe
authors.initials: P
authors.lastname: Grellier
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dubois
mesh_terms: D001483:Base Sequence; D002264:Carboxylic Acids / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development; D060327:Solid-Phase Synthesis Techniques / Q000379:methods*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D013876:Thiophenes; D051231:Farnesyltranstransferase