malaria research community

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02 Nov

A range of compounds are ready for testing with more coming.

Published by pylioja

Subject 

Request for Help

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!

17 Oct

Where Else Have the Aryl Pyrroles been Evaluated?

Published by MatTodd

Subject 

Miscellaneous

Last week I was talking with Lei Liu from Tsinghua University, who was visiting Sydney to give a talk on his synthetic methodology research. I showed him the compounds that are the starting point of the open source drug discovery project for malaria, the arylpyrrole set.

09 Oct

TCMDC-123812 and 123794, pending purification.

Published by pylioja

Subject 

Request for Help

I'm now fairly confident that I've made TCMDC-123794 and TCMDC-123812. By fairly confident I mean that I've got a reasonable looking but crude 1H NMR and low res. mass spec of both of the compounds. They are not clean by NMR after a column and the yield of the reaction was pretty bad (~20%). Still this isn't too bad for a first go, using a quick and dirty acid chloride. Most of the mass seems to go toward turning the acid into the anhydride.

21 Sep

Now we're getting somewhere but not with the oxidation

Published by pylioja

Subject 

Miscellaneous

Ok now I'm getting close to TCMDC-123812/123794. A slight change of tack for the alternative core synthesis seems to have paid off. First alkylation of ethyl acetoacetate with chloroacetone and then condensation with 4-fluoroaniline appears to have given the pyrrole with an ester on the 3-position quite nicely in 61% yield over the two steps after recrystallisation (PMY 8-1). Sometimes it just pays to change the plan completely when you feel like progress is slow.

19 Sep

Update on TCMDC-123812 and TCMDC-123794: Oxidation issues

Published by pylioja

Subject 

Rants

In the last couple of weeks my time has mostly been spent trying to figure out whats going on in the oxidation of pyrrole-3-carbaldehyde to the corresponding acid.
Reaction Scheme PY3_5.png

Known Near Neighbours of Initial Tres Cantos Leads

Published by MatTodd on 28 August 2011 - 7:01am

We're starting with the resynthesis of two leads from the GSK Tres Cantos dataset. The obvious question is: are there other, related structures in the dataset that might give us information on what to change next?

 

Biological Evaluation of Arylpyrrole Series

Published by MatTodd on 27 August 2011 - 12:51pm

New Stuff:
Online lab book hosting bioactivity data is here.
First set of compounds have been evaluated (Jan 2012) - here.
Background:

A list of what's needed in the OSDD Malaria project

Published by MatTodd on 27 August 2011 - 12:35pm

Main: Comment/Analysis on Initial Bioactivity Data

We have some excellent first results. What to do next?

 

Resynthesis of TCMDC-123812 and TCMDC-123794 (ELN)

Need: advice on oxidation of pyrrole-3-carbaldehydes - here. Through a work-around, these syntheses are complete, but we could still ue advice on the step above. Done

 

Druggability of the Arylpyrrole leads (TCMDC-123794 etc)

Published by MatTodd on 27 August 2011 - 12:25pm

Project is starting with a couple of leads from the GSK Tres Cantos set. There is a newly-published analysis of the druggability of the compounds in the original data set. The arylpyrrole series is listed as one of the most promising (though the Aryl-F is missing in the published paper - presume that is a clerical error).
 

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