title: Synthesis and biological evaluation of 4-amino derivatives of benzimidazoquinoxaline, benzimidazoquinoline, and benzopyrazoloquinazoline as potent IKK inhibitors.
abstract: We have recently identified BMS-345541 (1) as a highly selective and potent inhibitor of IKK-2 (IC50 = 0.30 microM), which however was considerably less potent against IKK-1 (IC50 = 4.0 microM). In order to further explore the SAR around the imidazoquinoxaline tricyclic structure of 1, we prepared a series of tetracyclic analogues (7, 13, and 18). The synthesis and biological activities of these potent IKK inhibitors are described.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, 100 boul. de l'Industrie, Candiac, Que., Canada J5R 1J1. francis.beaulieu@bms.com
authors.forename: Francis
authors.initials: F
authors.lastname: Beaulieu
authors.forename: Carl
authors.initials: C
authors.lastname: Ouellet
authors.forename: Edward H
authors.initials: EH
authors.lastname: Ruediger
authors.forename: Makonen
authors.initials: M
authors.lastname: Belema
authors.forename: Yuping
authors.initials: Y
authors.lastname: Qiu
authors.forename: Xuejie
authors.initials: X
authors.lastname: Yang
authors.forename: Jacques
authors.initials: J
authors.lastname: Banville
authors.forename: James R
authors.initials: JR
authors.lastname: Burke
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Gregor
authors.forename: John F
authors.initials: JF
authors.lastname: MacMaster
authors.forename: Alain
authors.initials: A
authors.lastname: Martel
authors.forename: Kim W
authors.initials: KW
authors.lastname: McIntyre
authors.forename: Mark A
authors.initials: MA
authors.lastname: Pattoli
authors.forename: F Christopher
authors.initials: FC
authors.lastname: Zusi
authors.forename: Dolatrai
authors.initials: D
authors.lastname: Vyas
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000494:pharmacology; D011810:Quinoxalines / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D001562:Benzimidazoles; D006576:Heterocyclic Compounds, 4 or More Rings; D011799:Quinazolines; D011804:Quinolines; D011810:Quinoxalines; D051550:I-kappa B Kinase