OSA Meeting Friday January 22nd 2021

[danaklug]

Meeting Jan 22nd 2021 at 2pm UK time at https://ucl.zoom.us/j/92800004715. This page follows on from #51.

Recording is here.

On the call:

1. Screening
   a) Potency
   New targets discussed in previous two meetings summarized in the image below.
   

Next potency screen will include any of the above targets that have been successfully synthesized, along with NEU compounds from @loriferrins (#48).

b) Human Cytotox
Underway in the lab of Andreas Schatzlein. This is also to test the metal-binding potential of the 2-pyridyl system. Updates will be at issue #3 .

@loriferrins has shared tox data on several related compounds, located in the Sample Contributions repository. Action on @danaklug to summarize and integrate into master OSA molecules spreadsheet.

2. Synthetic Chemistry
   No updates this week. @danaklug back in lab early/mid-Feb. Synthetic protocols from @loriferrins for the one-pot procedure (outlined below) are here. As per @MFernflower’s suggestion, a Google doc shopping list has been created. @danaklug to place orders by end of Jan.
   

3. in vitro PK
   Hypha results are in at Hypha Results (Jan 2021) #50 and will be discussed there. No action currently needed.

4. Community updates
   a) Newsletters. Action on @mattodd to write the second newsletter
   There is a Google form for sign-up here. Link has been added to OSA GH landing page. Action on @danaklug , also to copy over existing newsletter recipient names to the sheet.

5. Molecule contributions
   Terms discussed in Acceptable Terms for Molecule Donations? #45, with new revision (discussed more at Donating Molecules to Open Source Drug Discovery Projects mattodd/blog#1). Terms have been updated on OSA Series 2 wiki and on the Google form here.

6. Mechanism of Action
   Results received via email and have been shared here
   Discussion at Mechanism of action #15. Action on @edwintse to ensure the data are also installed on Labarchives and linked to Github, to ensure we don't lose such crucial files.
   Action on @mattodd to organise consultation on meaning of results.

7. Series Origin/Similarity Landscape
   GSK conversation here. @mattodd has incorporated into wiki.

8. ELN
   @danaklug or @edwintse to try again (Action) Labarchives' molecule sketching facility to see if the ELN page is Google-able. i.e. sketch a molecule from OSA using the drawing facility, and check each day to see if it is indexed. ELN pages on which strings have been manually pasted are indexed (@mattodd checked this). Can we do away with manual strings pasting? Separately, @mattodd found that the OSA molecule spreadsheet is not indexed. @drc007 said he would check this out (Action).

AOB

• @mattodd mentioned the value of having a Twitter Bot that takes a molecule from the OSA spreadsheet and tweets out the structure with the strings and with a page where it is clear what the use of the molecule is. This allows for human to spot the molecules that OSA requires. Action on @mattodd to outline what this would entail. Done at Hey Chemists! Planetary Forge Twitter Bot mattodd/blog#2

• (ongoing -> install in wiki as a way of working) @mattodd also reminded people to keep an eye on sites such as Enamine, Manifold and Mcule, to check whether any molecules might be commercially available. We should always try to make the challenging molecules in the lab, and buy the others. Action on @edwintse to include this in wiki somewhere logical.

Actions (can be checked as complete after the meeting).

• ACTION ITEM: Mat to write second newsletter.
• ACTION ITEM: Dana to assemble shopping list for immediate purchase for both new ideas (e.g. benzimidazole) and one-pot procedure from Lori.
• ACTION ITEM: Dana and Ed to look into whether manual strings are still needed in Labarchives, or whether molecule sketching facility is sufficient.
• ACTION ITEM: Ed to outline on wiki how we should keep in mind searches for commercially-available molecules from various suppliers, in parallel to the in-house synthetic chemistry.
• ACTION ITEM: Chris to look into why the OSA molecule sheet is not Google-indexed.
• ACTION ITEM: Dana to dig up and summarise Lori's tox/metabolic data on related compounds.
• ACTION ITEM: This meeting to be posted on YouTube.

[MFernflower]

@danaklug I hate being a nitpick but in the discussed compounds graphic one of the compounds I proposed is missing:

CC1=CC=C(SC2=C(N=C3CCCN23)C2=NC=CC=C2)C=C1

[mattodd]

You mean this? I'd not picked up on that in the notes, but fine. The RHS ring's obvs less important than the N -> S change or the nature of the para substituent.

[MFernflower]

@mattodd @danaklug That is the missing compound

We should be able to use the same arylation protocol for that and Chris Swain's structure hop

NaH in THF 0 °C-rt for 5 h - some papers recommend adding 1 mol% of tetrabutylammonium iodide for really fussy substrates - https://www.organic-chemistry.org/abstracts/lit1/961.shtm

[MFernflower]

@mattodd reason P-methyl was chosen is cause fluorochem.co.uk sells para-thiocresol in 50 gram bottles for 20 quid

[danaklug]

Closing - link to this issue has been added to the Project Meetings wiki.