Send 10-15 Compounds to Sue Charman for in vitro DMPK and Solubility

[mattodd]

Sue Charman can run in vitro DMPK and solubility on up to 10-15 compounds from Series 4. We need to send 5-7 mg to Monash.

Question therefore: for which of the compounds in the current batch (http://malaria.ourexperiment.org/biological_data/10048) do we have a remaining 5-7 mg?

@JoannaUbels @alintheopen @tscmacdonald can you please give the ID's for the relevant compounds you've made for which we have these amounts?

[mattodd]

Ping @alintheopen @tscmacdonald @JoannaUbels - can we action this, please - i.e. can you each suggest some compounds for which we have 5-7 mg? We have to send these off ASAP. Prioritise those compounds we know (now) are actives, followed by any compounds that have since been made. If the compounds don't have OSM numbers yet, put structures in the below. Let's get together the list (on Wed - want the list before the meeting) and then see how many we have to send.

[tscmacdonald]

I have enough of TM 9, TM 14, TM 19, and TM 26. Of those, TM 14 is active but has already been tested quite comprehensively (we were making to reconfirm data)

My current available amides:

Top row are sitting pure in >50 mg quantities in the fridge, the other four (methoxy phenyl and token nitrophenyl) are currently hydrazones but should be cyclised by the end of the week.

[alintheopen]

Thanks Tom, we are having a short meeting this arvo re: this issue. Should the list include MMV compounds too @mattoddchem?

On Wed, Jul 2, 2014 at 1:15 PM, tscmacdonald notifications@github.com wrote:

I have enough of TM 9, TM 14, TM 19, and TM 26. Of those, TM 14 is active but has already been tested quite comprehensively (we were making to reconfirm data)

My current available amides: [image: amides 2] https://cloud.githubusercontent.com/assets/6529539/3451430/ce7eea68-0196-11e4-891c-3ec6efa9f3fb.png

Top row are sitting pure in >50 mg quantities in the fridge, the other four (methoxy phenyl and token nitrophenyl) are currently hydrazones but should be cyclised by the end of the week.

— Reply to this email directly or view it on GitHub https://github.com/OpenSourceMalaria/OSM_To_Do_List/issues/213#issuecomment-47733341 .

[mattodd]

Can include MMV compounds that we've made and for which the wiki mentions no metabolic studies, sure. Let's see what's available to send, then whittle down the list if needed.

[alintheopen]

Right, the first figure shows all compounds that are ready and their activity status: The second figure shows compounds that we very nearly have that we could also consider sending for testing if we can send them next week.

[mattodd]

OK, I'd recommend (numbering corresponds to your latest scheme, Alice): 2 (acts as control - I'm surprised by the existing solubility measurement, on the wiki) 5 (major modification to ring, might expect lower sol) Either 10 or 11 12 The others are a gamble (since we don't know potency), but could we prioritise based on cLogP? So, one amide, one phenol, one ether and one chiral ether? If that's OK (say if so) I'll contact Sue to warn her and ensure that our sending these is still OK. Proceed as-is with the "one step away's" first in preference to the "underways" - the advice from the ESAC is to go for very low logP's and that may mean we stop the tweaking of these aromatics and introduce bigger mods. More on that at the meeting. i.e. if the "underways" are 3 steps away, it may not be worth taking through.