Series-2-Aminothiazoles
Screening of the stasis box (and a subsequent resynthesis project) identified MMV006357 a 2-aminothiazole with useful activity.
This compound is known in the literature and a search of ChEMBL identifies it as CHEMBL476339. It has been screened extensively:
- Malaria Screening (GlaxoSmithKline)
- Malaria Screening (Novartis)
- Leishmania Screening (Saint Jude)
In the literature it has been described as a potent Kca2.3 channel inhibitor (4 nM) DOI. This is a human calcium-activated potassium channel, does this channel or a homologue of it exist in ascomycota?
Try to confirm the mode of action
ChEMBL also contains details of several other molecules that are reported to be active at the same channel and it would be useful to evaluate them.
These include:
- The cyclic peptide Apimin (from honeybee venom) CHEMBL525408 (0.064 nM)
- A interesting cyclic polyamine CHEMBL3040285 (31 nM)
- This rather tame looking pyrazolo[1,5‐ a]pyrimidine CHEMBL472452 (350 nM).
If these are active it adds support to potassium channel blockade being the MOA.
Exploring the SAR of 2-Aminothiazoles
This structural class is well known in the literature and rather than embark on synthesis it would seem logical to see if we can access samples prepared for other projects.
A number of analogues were made in an leishmania project - seems to have been a DNDI project - can we get samples?
This interesting antimalarial screen - would not hurt to ask for samples?