title: Double Sonogashira reactions on dihalogenated aminopyridines for the assembly of an array of 7-azaindoles bearing triazole and quinoxaline substituents at C-5: Inhibitory bioactivity against Giardia duodenalis trophozoites.
abstract: The synthesis of 2,3,5-trisubstituted 7-azaindoles as well as 2,5-disubstituted 7-azaindoles from 3,5-dihalogenated 2-aminopyridines is outlined. Using a double Sonogashira coupling reaction on 2-amino-3,5-diiodopyridine followed by the Cacchi reaction the synthesis of 2,3,5-trisubstituted 7-azaindoles was accomplished. In addition, using two sequential Sonogashira coupling reactions on 2-amino-5-bromo-3-iodopyridine and a potassium t-butoxide mediated ring closure reaction resulted in the assembly of 2,5-disubstituted 7-azaindoles. The 5-alkynyl substituent of the azaindole was easily converted into both quinoxaline and triazole substituents, the latter utilizing an alkyne-azide cycloaddition reaction. Some of these azaindole derivatives showed very promising biological activity against the gastrointestinal protozoal parasite Giardia duodenalis.
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits 2050, Johannesburg, South Africa.
authors.forename: Tlabo C
authors.initials: TC
authors.lastname: Leboho
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits 2050, Johannesburg, South Africa.
authors.forename: Somnath
authors.initials: S
authors.lastname: Giri
authors.affiliation: Environmental Futures Research Institute and the School of Natural Sciences, Griffith University, Nathan Campus, 170 Kessels Road, Nathan, Queensland 4111, Australia.
authors.forename: Inessa
authors.initials: I
authors.lastname: Popova
authors.affiliation: Environmental Futures Research Institute and the School of Natural Sciences, Griffith University, Nathan Campus, 170 Kessels Road, Nathan, Queensland 4111, Australia.
authors.forename: Ian
authors.initials: I
authors.lastname: Cock
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits 2050, Johannesburg, South Africa.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Michael
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits 2050, Johannesburg, South Africa. Electronic address: Charles.deKoning@wits.ac.za.
authors.forename: Charles B
authors.initials: CB
authors.lastname: de Koning
mesh_terms: D000631:Aminopyridines / Q000737:chemistry*; D000977:Antiparasitic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016829:Giardia lamblia / Q000187:drug effects / Q000254:growth & development; D054879:Halogenation; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011810:Quinoxalines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*; D053058:Trophozoites / Q000187:drug effects
chemical_list: D000631:Aminopyridines; D000977:Antiparasitic Agents; D001372:Aza Compounds; D007211:Indoles; D011810:Quinoxalines; D014230:Triazoles
keywords: 7-Azaindoles; Giardia duodenalis; Sonogashira reactions