title: The synthesis of 2-nitroaryl-1,2,3,4-tetrahydroisoquinolines, nitro-substituted 5,6-dihydrobenzimidazo[2,1-a]isoquinoline N-oxides and related heterocycles as potential bioreducible substrates for the enzymes NAD(P)H: quinone oxidoreductase 1 and E. coli nitroreductase.
abstract: A series of 2-nitroaryl-1,2,3,4-tetrahydroisoquinolines 10 and nitro-substituted 5,6-dihydrobenzimidazo[2,1-a]isoquinoline N-oxides 11 have been synthesised and evaluated as potential bioreducible substrates for the enzymes NAD(P)H: quinone oxidoreductase 1 (NQO1) and Escherichia coli nitroreductase (NR). Also prepared and evaluated were 2-(3,5-dinitropyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline 12 and 5,6-dihydro-10-nitropyrido[3″,2″:4',5']imidazo[2',1'-a]isoquinoline 12-oxide 13. Both compounds 10b and 13 were reduced faster by human NQO1 than by CB-1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide].
authors.affiliation: Morvus Technology Ltd, Tŷ Myddfai, Llanarthne, Carmarthen SA32 8HZ, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Burke
authors.forename: Lai Chun
authors.initials: LC
authors.lastname: Wong
authors.forename: Terence C
authors.initials: TC
authors.lastname: Jenkins
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Knox
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Stanforth
mesh_terms: D001388:Aziridines / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D009601:Nitroreductases / Q000378:metabolism*; D010087:Oxides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D001388:Aziridines; D006571:Heterocyclic Compounds; D007546:Isoquinolines; D010087:Oxides; C100099:tretazicar; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D009601:Nitroreductases; C039109:isoquinoline