Aminothiazoles : DNDi analogues

[bendndi]

Here is a list of around 140 analogues to MMV006357 which were made for DNDi (by Advinus) as part of a leishmaniasis project. I've only included data for cytotoxicity, metabolic stability and solubility here. Feel free to have a look through and draw conclusions.

Note that compounds tend to be very tightly plasma protein bound, and in general only modest PK was achieved for the series.

Also note there seems to be significant species variability in the microsomal stability across the series (Hamster data was generated since this was the relevant species for the infection model)

We're currently looking into the possibility of sourcing samples from this list; I'll keep you updated as to if this is possible

@mattodd perhaps best option here is to put this list in google docs as with the fenarimol series

DNDI aminothiazoles list.xlsx

[drc007]

@bendndi Thanks for this. Whilst cytotoxicity might compromise interpretation I suspect PPB binding and metabolic turnover should not be too much of an issue in the screening assays @wwjvdsande (but very useful info to have up front).

[wwjvdsande]

No I don't think that in the in vitro assays it will matter @drc007. We don't include serum in the culture media. In the larvae it will matter

[bendndi]

UPDATE: Unfortunately we no longer have access to samples of any of the compounds from this series. Synthesis will be required if we want to validate / test any of these compounds.

[drc007]

@bendndi That is a shame. I had a look at the excel table you kindly provided and a number are commercially available. I've annotated the list with suppliers and codes.

DNDI.aminothiazolesUpdated.xlsx

[drc007]

@wwjvdsande These types of structures are quite common, if I was to put out a twitter request for people to donate samples would you be interested?

[wwjvdsande]

I think it could be a good idea to test. The final goal is to find some alternative compounds with activity against mycetoma. The fenarimols are a good starting point but should not be the only starting point. I think it is wise to spread our chances. If we do a similar set up as with the fenarimols and do an initial screening at two concentrations we can take it further from there. I would propose to screen 45 compounds for this in two concentrations at first and than based on these initial data work or way further. Any other suggestions?

[drc007]

I've added a range of identifiers to the list. ChEMBL and PubChem ID to give an indication of known biological activity. ZINC, eMolecules, Mcule to indicate where compounds are commercially available. DNDIaminothiazoles_list_suppliers.xlsx

[MFernflower]

8 Cross reference