title: 2-Carbaborane-3-phenyl-1H-indoles--synthesis via McMurry reaction and cyclooxygenase (COX) inhibition activity.
abstract: Cyclooxygenase-2 (COX-2) inhibitors have been the focus of medicinal chemistry efforts for years, and many compounds that exhibit high selectivity and affinity have been developed. As carbaboranes represent interesting pharmacophores as phenyl mimetics in drug development, this paper presents the synthesis of carbaboranyl derivatives of COX-2-selective 2,3-disubstituted indoles. Despite the lability of carbaboranes under reducing conditions, 2-carbaborane-3-phenyl-1H-indoles could be synthesized by McMurry cyclization of the corresponding amides. Whereas the meta-carbaboranyl-substituted derivatives lacked COX inhibitory activity, an ortho-carbaboranyl analogue was active, but showed a selectivity shift toward COX-1.
authors.affiliation: Institut für Radiopharmazie, Helmholtz-Zentrum Dresden-Rossendorf, Bautzner Landstrasse 400, 01328 Dresden, Germany. m.laube@hzdr.de
authors.forename: Markus
authors.initials: M
authors.lastname: Laube
authors.forename: Wilma
authors.initials: W
authors.lastname: Neumann
authors.forename: Matthias
authors.initials: M
authors.lastname: Scholz
authors.forename: Peter
authors.initials: P
authors.lastname: Lönnecke
authors.forename: Brenda
authors.initials: B
authors.lastname: Crews
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
authors.forename: Torsten
authors.initials: T
authors.lastname: Kniess
authors.forename: Evamarie
authors.initials: E
authors.lastname: Hey-Hawkins
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003500:Cyclization; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051379:Mice; D008958:Models, Molecular; D012756:Sheep
chemical_list: D001896:Boron Compounds; D052246:Cyclooxygenase 2 Inhibitors; D007211:Indoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2