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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...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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WILEY-VCH Verlag
2009
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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. |
format | Text |
id | pubmed-2929374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | WILEY-VCH Verlag |
record_format | MEDLINE/PubMed |
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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