title: Diversity oriented synthesis and IKK inhibition of aminobenzimidazole tethered quinazoline-2,4-diones, thioxoquinazolin-4-ones, benzodiazepine-2,3,5-triones, isoxazoles and isoxazolines.
abstract: The derivatization of resin-bound aminobenzimidazole toward the parallel solid-phase synthesis of aminobenzimidazole tethered pharmacologically important heterocycles such as quinazoline-2,4-diones, thioxoquinazolin-4-ones, benzodiazepine-2,3,5-triones, isoxazoles and isoxazolines is reported. All the compounds were tested for IKK inhibition. Only one compound elicited significant inhibition of IKKε, TBK-1 and IKK2.
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA.
authors.forename: Sureshbabu
authors.initials: S
authors.lastname: Dadiboyena
authors.affiliation: Laboratory of Selective Organic Chemistry & Biological Activity, Faculty of Science of Tunis, University El Manar, 2092, Tunisia.
authors.forename: Aïcha
authors.initials: A
authors.lastname: Arfaoui
authors.affiliation: Laboratory of Selective Organic Chemistry & Biological Activity, Faculty of Science of Tunis, University El Manar, 2092, Tunisia.
authors.forename: Hassen
authors.initials: H
authors.lastname: Amri
authors.affiliation: Torrey Pines Institute for Molecular Studies, General Atomics Court, San Diego, CA 92121, USA.
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Piedrafita
authors.affiliation: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA. Electronic address: adeln@tpims.org.
authors.forename: Adel
authors.initials: A
authors.lastname: Nefzi
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D001570:Benzodiazepinones / Q000737:chemistry*; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007555:Isoxazoles / Q000737:chemistry*; D007700:Kinetics; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D052999:Quinazolinones / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques
chemical_list: D001562:Benzimidazoles; D001570:Benzodiazepinones; D007555:Isoxazoles; D047428:Protein Kinase Inhibitors; D052999:Quinazolinones; C031000:benzimidazole; D051550:I-kappa B Kinase
keywords: 1,3-Dipolar cycloaddition; Aminobenzimidazoles; Benzodiazepinetriones; Heterocycles; Intramolecular cyclization; Isoxazoles; Isoxazolines; Quinazolinediones; Solid-phase synthesis; Thioxoquina-zolinones