The Synaptic Leap

The following compounds have been identified as potential antimalarial drugs by GSK-Tres Cantos.

The top compound, known hereafter as 'compound 3', can be found on ChEMBL and ChemSpider:
https://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL535225 - ChEMBL
https://www.chemspider.com/Chemical-Structure.15995932.html?rid=1e70c7d6... - ChemSpider
 
As can the bottom compound, known hereafter as 'compound 4':

I've been working for six weeks now with the Todd Research Group at Sydney University as part of an undergraduate summer research program. The aim of my project is to synthesise analogues of this group of hits from the  antimalarial dataset released by GSK. They are referred to here as 'near neighbours' because they share the arylpyrrole moiety present in the two hits (TCMDC 123812 and 123794) Paul has been working on, but have a thiazolodinone side chain. The major components of my project are:

We have received encouraging biological results for the analogues we sent for testing before Christmas. Mat has discussed this here on TSL and on G+. Our best hit came from the "near-neighbour" compound and the original GSK hits came out slightly less active than in their original high throughput screen. However, Paul Willis at MMV rates TCMDC-123794 as a better lead than PMY 14-1 (TSL post).

 I have just packaged up TCMDC-123794 (PMY 11-2) and -123812 (PMY 10-2) along with the parent acid (PMY 8-2), ester (PMY 6-1), aldehyde (PMY 2-4), near neighbour analogue (PMY 14-1) and also the acylurea by-product (PMY 12-1-A). These have been sent to GSK Tres Cantos where the original study was carried out for further testing.

I'm now happy with the data for TCMDC-123812 and TCMDC-123794. A bit of usual practical annoynce with TCMDC-123794 caused some trivial issues, namely a bit of repurification and acetone in the final spectra. These have now been taken care of and the compounds are ready for testing!
I've summarised the various intermediates and other compounds that are in the works on OpenWetWare. Please get in touch if you're interested in testing them.