Identification of Old Paul Willis Molecule Suggestions that Need Adding to DCNYS

[mattodd]

@mbhebhe can you please take a look at the Github file Wiki Files>DCNYS>Paul Willis_Thienopyrimidine new targets. Please can you see whether any of the compounds in the Chemdraw file have been completed (vs the list of all compounds made to date)? If they have, create a new ("V2") version of this Chemdraw file that shows which compounds have been made (black, with an OSM number) and which are still needed (in red). The ones that are still needed will need to be added to the DCNYS page, and we can create a new Issue for that when the required structures have been identified.

[mbhebhe]

What's written in blue is mine. Six of the compounds have been made but one (OSM-S-145), has not been sent for biological evaluation yet. The ones in red need to be made, for some of them we have the two halves that need need to be coupled together (hopefully are in the fridge).

[drc007]

@mattodd @mbhebhe Sorry if I have missed it, but have we remade and tested the original hit?

[mbhebhe]

@drc007 yes we have, it has been made and all the data is here on the wiki. I recently made more and it has been sent to Dundee for biological evaluation and if its good, I will send some to Ho Leung's lab.

[MFernflower]

A wee bit unrelated but has this compound ever been tested? @mattodd @mbhebhe

Should be easy as pie to make!!!!

This is a intrinsically harder idea to produce but is inspired by the fact the drug might be working as a ATP mimic:

[mattodd]

This is @mbhebhe 's out-of-office vacation reply service. The tetra-methyl is not something I'd be keen to go for given the lack of activity of TF18-1 above. Other compounds are listed in the wiki, e.g. https://github.com/OpenSourceMalaria/Series3/wiki/All-Analogs-Evaluated-to-Date The compound with the two methyls on the northern NH2 was apparently made but not evaluated if I'm reading that correctly (OSM-S-145).

[MFernflower]

Seems like it would be wise to re-synthesize some OSM-S-145? @mbhebhe @mattodd Also see the second idea I posted about a diamino compound (based on the prediction that s3 drugs mimic atp)

[mbhebhe]

OSM-S-145 should be resynthesized, yes. The diamino compound can be made, the dichloro can be purchased and then we should be able to brominate and then aminate and then couple

[MFernflower]

@mbhebhe Have not seen updates from you in a while - has synthesis of any of the ring analogues been completed as of late?

[mbhebhe]

Not complete yet, they are still in progress

[MFernflower]

Closing this - it appears that OSM-S-145 and OSM-S-437 need to be re-synthesized and send off for testing

@mbhebhe can you track down the finished osm-s-145?