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Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase

Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP (1, 1-(1-benzo[b]thiophen-2-yl-cyclohexyl) piperidine) was found to be a competitive inhibitor of...

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Autores principales: Patterson, Stephen, Jones, Deuan C, Shanks, Emma J, Frearson, Julie A, Gilbert, Ian H, Wyatt, Paul G, Fairlamb, Alan H
Formato: Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929374/
https://www.ncbi.nlm.nih.gov/pubmed/19557802
http://dx.doi.org/10.1002/cmdc.200900098
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author Patterson, Stephen
Jones, Deuan C
Shanks, Emma J
Frearson, Julie A
Gilbert, Ian H
Wyatt, Paul G
Fairlamb, Alan H
author_facet Patterson, Stephen
Jones, Deuan C
Shanks, Emma J
Frearson, Julie A
Gilbert, Ian H
Wyatt, Paul G
Fairlamb, Alan H
author_sort Patterson, Stephen
collection PubMed
description Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP (1, 1-(1-benzo[b]thiophen-2-yl-cyclohexyl) piperidine) was found to be a competitive inhibitor of the enzyme (K(i)=1 μm) and biologically active against bloodstream T. brucei (EC(50)=10 μm), but with poor selectivity against mammalian MRC5 cells (EC(50)=29 μm). Analogues with improved enzymatic and biological activity were obtained. The structure–activity relationships of this novel series are discussed.
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spelling pubmed-29293742010-09-09 Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase Patterson, Stephen Jones, Deuan C Shanks, Emma J Frearson, Julie A Gilbert, Ian H Wyatt, Paul G Fairlamb, Alan H ChemMedChem Full Paper Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP (1, 1-(1-benzo[b]thiophen-2-yl-cyclohexyl) piperidine) was found to be a competitive inhibitor of the enzyme (K(i)=1 μm) and biologically active against bloodstream T. brucei (EC(50)=10 μm), but with poor selectivity against mammalian MRC5 cells (EC(50)=29 μm). Analogues with improved enzymatic and biological activity were obtained. The structure–activity relationships of this novel series are discussed. WILEY-VCH Verlag 2009-08-03 2009-06-25 /pmc/articles/PMC2929374/ /pubmed/19557802 http://dx.doi.org/10.1002/cmdc.200900098 Text en Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim http://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation.
spellingShingle Full Paper
Patterson, Stephen
Jones, Deuan C
Shanks, Emma J
Frearson, Julie A
Gilbert, Ian H
Wyatt, Paul G
Fairlamb, Alan H
Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase
title Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase
title_full Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase
title_fullStr Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase
title_full_unstemmed Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase
title_short Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase
title_sort synthesis and evaluation of 1-(1-(benzo[b]thiophen-2-yl)cyclohexyl)piperidine (btcp) analogues as inhibitors of trypanothione reductase
topic Full Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929374/
https://www.ncbi.nlm.nih.gov/pubmed/19557802
http://dx.doi.org/10.1002/cmdc.200900098
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