"Ketone" 3 Changes to Molecule

[liana-alves]

Hi, Dora and I have been working at the "Ketone" synthesis. And for part of our final superlab project, we want to look at 3 modifications of the "Ketone" that make it an even better potential drug. Any suggestions how we could change the molecule? In other words, modifications that could be made that may affect its solubility, stability, or potency in a significant way? And why those modifications would be better?

Here is the Ketone

Thanks!

[MFernflower]

Why not do 3,4 difluorophenyl on the left hand side?

[mattodd]

Hi @liana-alves . First things first. You've written an "orphan post" with no links out to anything else. This is no good because we can easily lose track of what's been discussed. Can you please edit your original post to link to the most relevant Github issues, your lab notebook and the current summary of where we're up to on this target, which is on the wiki here?

To your question: well, I think making the ketone itself remains the top priority, no? Any modifications are likely to make the molecule more difficult or expensive to make, unless there are relevant starting materials you can buy that would take you to the endpoint more quickly? So we can always append groups to improve solubility, or potency (likely @MFernflower 's suggestion will do that, based on what we know) but these would normally come after we've developed the methods we need for the key bond formations.

[MFernflower]

@mattodd 3,4 difluorophenylacetic acid runs about 50 usd a gram... (just need to esterfy with isobutanol) I wonder if it is worth shifting the singular target ketone from 3,4 H to 3,4 F?? @liana-alves @rbroadrup-HC

[drc007]

@liana-alves Perhaps the best way to decide what to make next is to look at similar analogues. OSM-S-202 has a carbonyl in the same position as the ketone, but it is an amide. Which other amides have shown good activity? Have a look at http://malaria.ourexperiment.org/biological_data/10456/IC50_determination_of_Compounds_Sent_to_GSK.html @mattodd

[liana-alves]

@MFernflower @drc007 Thanks for all the suggestions. @mattodd you are correct, making the Ketone is still the top priority for, this was more of a thought experiment on what parts of the molecule make it a candidate for drug usage, and how we could hypothesize any potential improvements.

[MFernflower]

@liana-alves What step of the chlorination process failed?