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OpenSourceMalaria / OSM_To_Do_List

Action Items in the Open Source Malaria Consortium
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Trends in logD vs metabolic stability? #333

Open mattodd opened 9 years ago

mattodd commented 9 years ago

We have measured logD data and metabolic clearance data for 8 compounds in Series 4, from Monash. The data are all contained in the main sheet, but I've extracted the data into this daughter sheet.

The plot of log D vs log CLint appears to give a fair scatter, with perhaps a vague trend for the MLM data.

Can anyone spot any clear trends here? I can't. Clearly the idea is that if we lower logD we might improve clearance and half-lives in a way that we're not doing currently.

Feel free to add to the daughter sheet. You can drag and drop images below.

Can discuss in Monday's meeting #317

drc007 commented 9 years ago

Now we have a few measured values I thought it might be useful to compare with calculated values. As you can see in the table below ChemDraw is poor a predicting values, ChemAxon seems to be better.

logp

mattodd commented 9 years ago

Very nice Chris. Where are the data from which you generated the image? The Chemaxon algorithm seems to be a decent predictor going forward, at least as a first pass. Presumably it's predicting for pH 7.4? The chemdraw cLogP seems to be not useful.

drc007 commented 9 years ago

All calculated within vortex

Sent from Chris's iPhone

On 28 Jul 2015, at 13:51, Mat Todd notifications@github.com wrote:

Very nice Chris. Where are the data from which you generated the image? The Chemaxon algorithm seems to be a decent predictor going forward, at least as a first pass. Presumably it's predicting for pH 7.4? The chemdraw cLogP seems to be not useful.

— Reply to this email directly or view it on GitHub.

pluralise commented 8 years ago

logD - metabolism data plots, using data from the daughter sheet mentioned in the original post

In each plot, the matched pair MMV672723 and MMV672727 are the darker spots (image where R1 is O and F respectively)

image

image

mattodd commented 8 years ago

That's fantastic, @MJTarnowski . What do you conclude? Do these trends tell us anything relevant about the discussion going on over in #358 - specifically the issue (here) related to whether the periphery of the compounds is responsible for fast clearance, or whether it's the triazolopyrazine ring that is the culprit?