Next steps

[MFernflower]

Since data has come back on the first batch of N-alkyl tricyclics made by @P-Rayner and his lab indicating only weak antifungal effects compared to the NEU/Curaxin type compounds, I feel like we need to move to compounds that are more similar to CBL0137 - as it was found that removing the N-ethylisopropylamine "tail" rendered the drugs unable to kill trypanosomes:

I have compiled a list of possible compounds to make for groups who may be interested in such - I.E @eloizidou @P-Rayner @lferrins

https://github.com/OpenSourceMycetoma/Series-3-Phenothiazines/wiki/Desirable-Compounds-Not-Yet-Synthesised

These will be a bit harder to make then then original chlorpromazine hit but I feel like it would be worth it

[P-Rayner]

We will take a look at making some of these types of cores in the coming academic year. They aren't the most straightforward to make but we should be able to make some progress towards them.

[MFernflower]

@P-Rayner No idea if this would work but ambeed sells the tail section with a chloride attached to it https://www.ambeed.com/products/6306-61-2.html

I wonder if it would be possible to take the raw tricycle and this alkyl chloride and use phase transfer conditions to SN2 them into the finished drug?

http://phasetransfercatalysis.com/ptc_reaction/ptc-n-alkylation-of-carbazole-derivative/

[P-Rayner]

@MFernflower We had tried a few things similar (though not with the isopropylamine) this year with limited success. I plan to go via reductive aminations as they seem a bit more successful.

[MFernflower]

Sounds good - I assume you are going to go via this route? @P-Rayner

[P-Rayner]

Possibly, there are a few routes that look feasible but we will certainly give something similar to that a go.

[MFernflower]

@p-rayner Hope everything is going well, I know the first few weeks of the new college semester are normally quite hectic (I myself are currently taking prerequisite mathematics courses!) but I was wondering if there has been any work started on the next batch of tricyclic antifungals and if so where is the notebook where such work is being recorded since I do not see any updates in the ELN that was linked on the wiki.

[P-Rayner]

Students are due to get back in the lab in a couple of weeks and will be working on this through to about April/May. As you say, things are a bit hectic with the start of term but will update once we get going.