OSDDMalaria:OSDD Malaria Paper 1
- 1 Open Source Drug Discovery for Malaria - Highly Potent Compounds Derived from the GSK Arylpyrrole Set
Open Source Drug Discovery for Malaria - Highly Potent Compounds Derived from the GSK Arylpyrrole Set
Zoe Hungerford, School of Chemistry, The University of Sydney, NSW 2006, Australia
Matthew H. Todd, School of Chemistry, The University of Sydney, NSW 2006, Australia
Paul Ylioja, School of Chemistry, The University of Sydney, NSW 2006, Australia
Additional authors - add alphabetically if you contribute something substantial. Please include some public place you can be contacted, e.g. a G+ account.
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Malaria's continuing impact.
Emergence of resistance to artemisinin on the Thai-Myanmar border: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2960484-X/abstract.
The initial targets were TCMDC-123812 and its 4-aminoantipyrine derivative TCMDC-123794. The aryl pyrrole core was obtained via a Paal-Knorr cyclisation using 4-fluoroaniline and 2,5-hexanedione. This gave multi-gram quantities of the pyrrole that could be furnished with an aldehyde in good yield using Vilsmeier-Haack conditions. Unfortunately, the subsequent oxidation of this aldehyde failed to give the desired carboxylic acid in synthetically useful yields. Instead ethyl 2-acetyl-4-oxopentanoate was synthesised and cyclised to the desired pyrrole ester. Hydrolysis followed by conversion to the acid chloride and coupling with glycolamide side chains (xxx and xxx) gave both TCMDC-123812 and TCMDC-123794 in xxx and xxx% yield respectively.
The 2-iminothiazolidinone analogues were obtained from the pyrrole aldehyde and 2-phenyliminothiazolidin-4-one using conditions used by Roberts. These could then be converted to the acyl, cyclohexyl and acetonitrile derivatives...
Experimental Details for Novel Compounds
Identities of compounds are here
The original lab notebook entries and data can be found here
Experimental Details for Biological Evaluation
Description of the biological evaluation can be found here
Supporting Information Section
Insert details for known compounds here.
(Use PLoS style - see Gamo et al for an example, or the official guidelines are here. Arrange references below in alphabetical order of first author)
- Gamo FJ, Sanz LM, Vidal J, de Cozar C, Alvarez E et al (2010) Thousands of chemical starting points for antimalarial lead identification. Nature 465: 305-310 (DOI: 10.1038/nature09107)