Tomorrow we will be having an open chat with anyone who wants to pitch in about which compounds we should be making for the next round of testing. We've been talking about this for a while (phase 1, phase 2) and this the final call before we split some of the compounds into seperate jobs that teams can take on. In the mean time, I've made a few of the compounds we mentioned and I'm most of the way to a couple of others.

I thought I would just quickly summarise some of the hits that come up in ChEMBL-NTD for the core structures of the compounds we're working with at the moment. The most active compounds, the "near neighbours", contain both a 2-iminothiazolidinone and 2,5-dialkylpyrrole moiety.

We've just had a single crystal x-ray structure back for OSM-S-9 (PMY 35-1) confirming which isomer of the product we've been making.

The structure shows the acyl group on the N-phenyl nitrogen rather than on the iminothiazolidinone nitrogen. It's nice to have this cleared up.

There's something that we've been neglecting on our Labtrove ELN entries so far that we should probably deal with. Metadata. It would be great to add some more of this to our posts but the question is what would be most useful? Labtrove adds metadata in the same way as it add "Sections", i.e. it places them onto the menu on the right hand side. The problem with this is: if the precise yield is given in the metadata then it lists every single yield on the right hand side making for inconvinient reading.

It's exciting as usual on the project. We've submitted the three compounds for in-vivo oral evaluation in a mouse model. The original hits TCMDC-123812 and -123794 were submitted along with one of Zoe's near neighbours, ZYH 3-1. It's not the most active of our compounds with an IC50 of 26 nM, but its logP comes in at just under 5 or there abouts (see: http://www.thesynapticleap.org/node/384#comment-798). It's still pretty high so we'll see how it goes.

 The first results of bio-data for the 2nd round of compounds is back from the Avery group and Mat has summarised the results in his post here on synaptic leap and on Google+. We are seeing some very active compounds but as many people have pointed out, all of the highly active compounds have high logP value (ChemDraw calculated). This is something we've definitely noticed when synthesising the compounds themselves. 
 

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.

 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 (P