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Synthesis and evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase.
ChemMedChem. 2009 Aug; 4(8):1341-53.C

Abstract

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 microM) and biologically active against bloodstream T. brucei (EC(50)=10 microM), but with poor selectivity against mammalian MRC5 cells (EC(50)=29 microM). Analogues with improved enzymatic and biological activity were obtained. The structure-activity relationships of this novel series are discussed.

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Publisher Full Text
ncbi.nlm.nih.gov
doi.org
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Authors+Show Affiliations

Patterson S
Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
Jones DC
No affiliation info available
Shanks EJ
No affiliation info available
Frearson JA
No affiliation info available
Gilbert IH
No affiliation info available
Wyatt PG
No affiliation info available
Fairlamb AH
No affiliation info available

MeSH

AnimalsCell LineEnzyme InhibitorsHumansNADH, NADPH OxidoreductasesPhencyclidinePiperidinesStructure-Activity RelationshipThiophenesTrypanocidal AgentsTrypanosoma brucei brucei

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19557802

Citation

Patterson, Stephen, et al. "Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase." ChemMedChem, vol. 4, no. 8, 2009, pp. 1341-53.
Patterson S, Jones DC, Shanks EJ, et al. Synthesis and evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase. ChemMedChem. 2009;4(8):1341-53.
Patterson, S., Jones, D. C., Shanks, E. J., Frearson, J. A., Gilbert, I. H., Wyatt, P. G., & Fairlamb, A. H. (2009). Synthesis and evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase. ChemMedChem, 4(8), 1341-53. https://doi.org/10.1002/cmdc.200900098
Patterson S, et al. Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase. ChemMedChem. 2009;4(8):1341-53. PubMed PMID: 19557802.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis and evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) analogues as inhibitors of trypanothione reductase. AU - Patterson,Stephen, AU - Jones,Deuan C, AU - Shanks,Emma J, AU - Frearson,Julie A, AU - Gilbert,Ian H, AU - Wyatt,Paul G, AU - Fairlamb,Alan H, PY - 2009/6/27/entrez PY - 2009/6/27/pubmed PY - 2009/10/29/medline SP - 1341 EP - 53 JF - ChemMedChem JO - ChemMedChem VL - 4 IS - 8 N2 - 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 microM) and biologically active against bloodstream T. brucei (EC(50)=10 microM), but with poor selectivity against mammalian MRC5 cells (EC(50)=29 microM). Analogues with improved enzymatic and biological activity were obtained. The structure-activity relationships of this novel series are discussed. SN - 1860-7187 UR - https://www.unboundmedicine.com/medline/citation/19557802/Synthesis_and_evaluation_of_1__1__Benzo[b]thiophen_2_yl_cyclohexyl_piperidine__BTCP__analogues_as_inhibitors_of_trypanothione_reductase_ L2 - https://doi.org/10.1002/cmdc.200900098 DB - PRIME DP - Unbound Medicine ER -