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

Philip Burke; Lai Chun Wong; Terence Jenkins; Richard Knox; Stephen Stanforth

doi:10.1016/j.bmcl.2011.10.044

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

Philip Burke, Lai Chun Wong, Terence Jenkins, Richard Knox, Stephen Stanforth

Applied Sciences Department

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

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].

Original language	English
Pages (from-to)	7447-7450
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	21
Issue number	24
DOIs	https://doi.org/10.1016/j.bmcl.2011.10.044
Publication status	Published - 2011

Keywords

NAD(P)H
quinone oxidoreductase 1 (NQO1)
Escherichia coli nitroreductase
CB-1954
1
2
3
4-Tetrahydroisoquinolines
Benzimidazo[2
1-a]isoquinoline N-oxides

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Burke, P., Chun Wong, L., Jenkins, T., Knox, R., & Stanforth, S. (2011). 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. Bioorganic & Medicinal Chemistry Letters, 21(24), 7447-7450. https://doi.org/10.1016/j.bmcl.2011.10.044

Burke, Philip ; Chun Wong, Lai ; Jenkins, Terence et al. / 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. In: Bioorganic & Medicinal Chemistry Letters. 2011 ; Vol. 21, No. 24. pp. 7447-7450.

@article{fe193baec1c64817a04fb5f24968282c,

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].",

keywords = "NAD(P)H, quinone oxidoreductase 1 (NQO1), Escherichia coli nitroreductase, CB-1954, 1, 2, 3, 4-Tetrahydroisoquinolines, Benzimidazo[2, 1-a]isoquinoline N-oxides",

author = "Philip Burke and {Chun Wong}, Lai and Terence Jenkins and Richard Knox and Stephen Stanforth",

year = "2011",

doi = "10.1016/j.bmcl.2011.10.044",

language = "English",

volume = "21",

pages = "7447--7450",

journal = "Bioorganic & Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier",

number = "24",

}

Burke, P, Chun Wong, L, Jenkins, T, Knox, R & Stanforth, S 2011, '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', Bioorganic & Medicinal Chemistry Letters, vol. 21, no. 24, pp. 7447-7450. https://doi.org/10.1016/j.bmcl.2011.10.044

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. / Burke, Philip; Chun Wong, Lai; Jenkins, Terence et al.
In: Bioorganic & Medicinal Chemistry Letters, Vol. 21, No. 24, 2011, p. 7447-7450.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Burke, Philip

AU - Chun Wong, Lai

AU - Jenkins, Terence

AU - Knox, Richard

AU - Stanforth, Stephen

PY - 2011

Y1 - 2011

N2 - 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].

AB - 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].

KW - NAD(P)H

KW - quinone oxidoreductase 1 (NQO1)

KW - Escherichia coli nitroreductase

KW - CB-1954

KW - 1

KW - 2

KW - 3

KW - 4-Tetrahydroisoquinolines

KW - Benzimidazo[2

KW - 1-a]isoquinoline N-oxides

U2 - 10.1016/j.bmcl.2011.10.044

DO - 10.1016/j.bmcl.2011.10.044

M3 - Article

SN - 0960-894X

SN - 1464-3405

VL - 21

SP - 7447

EP - 7450

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 24

ER -

Burke P, Chun Wong L, Jenkins T, Knox R, Stanforth S. 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. Bioorganic & Medicinal Chemistry Letters. 2011;21(24):7447-7450. doi: 10.1016/j.bmcl.2011.10.044