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Everything to do with Open Source Malaria Series 3
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Commercially available compounds similar to OSM-S-106 (Late Jan 2019 search) #13

Open mbhebhe opened 5 years ago

mbhebhe commented 5 years ago

image

@cdsouthan did a search on compounds similar to our hit compound (OSM-S-106). There were 33 compounds; some are already in our OSM library, others are not commercially available and some are (picture above). So we need to decide which ones (of the list above) we should purchase and send to Dundee for biological evaluation.

See Issue #12 for more info

cdsouthan commented 5 years ago

Could @holeung manage a 3D overlay?

MFernflower commented 5 years ago

My vote is for these two molecules based on cost and overall lookalikeness of them to the s3 hit _vote

mbhebhe commented 5 years ago

I agree with @MFernflower. Although in the past not having a primary sulfonamide has reduced potency. I think doing a 3D overlay would be good.

MFernflower commented 5 years ago

I feel it's important for all to note that the only one with an exposed sulfonamide is going to cost upwards of 2000 usd to screen against malaria (unless @mbhebhe can take a shot at making it?)

MFernflower commented 5 years ago

I'd like to hear from @mbhebhe and/or @mattodd regarding a final opinion on this - I still think sending a few select or all? of the Enamine LTD compounds listed would be the best option

MFernflower commented 5 years ago

@holeung Would it be possible to dock some of these drugs to your model of the TRNA synthase?

mbhebhe commented 5 years ago

Sending all the enamine compounds is a good idea as they are not expensive.

cdsouthan commented 5 years ago

Fine, Ukraine chemists are good value :) However, best to do a precautionary independent purity check (but only later on the good hits)

MedChemProf commented 5 years ago

I second @cdsouthan 's purity check with one additional caveat. Multiple times I have seen hits from commercial vendors repeat and have a good purity profile via LCMS, but then subsequently fail following testing after in-house synthesis. Not a deal breaker, just something to be cognizant about.

cdsouthan commented 5 years ago

Ho hum - so pure but wrong? (welcome back @MedChemProf by the way :)

drc007 commented 5 years ago

As they say "Trust but verify".

MFernflower commented 5 years ago

Always good to verify your hits - especially when the hit is from a commercial library!

We should screen the products first and then verify the ones that show activity @mbhebhe

mattodd commented 5 years ago

Ok, so 1) There are two compounds we're interested in? What's the cost? Need 5 or 10 mg, roughly. 2) We ship to UCL, NMR, re-ship 2 mg to Dundee?

MFernflower commented 5 years ago

Price for the two molecules I proposed is gonna be 178 usd before shipping (but i think enamine has a UK distributor so shipping to UCL hopefully wont be that problematic)

https://www.enaminestore.com/catalog/Z196159998

https://www.enaminestore.com/catalog/Z373297698

I tagged this needs action because it seemed like there was a resurgence in interest regarding this topic @mattodd