OSA Meeting Friday Oct 1st 2021

[mattodd]

Meeting Oct 1st 2021 at 2pm UK time at https://ucl.zoom.us/j/92800004715. This page follows on from #93 and #89.

Recording: https://youtu.be/8fBrndO7fFk

On the call: @mattodd @drc007 @danaklug @edwintse @QSimpson @loriferrins @danielgedder @MFernflower and Thomas Kresina.

Going to start minutes/agenda from scratch, to refresh. Let's discuss:

1) New MRSA screening results #92 and the very nice SAR analysis from Dana in #94. Control compound OK. One potent compound, up against the ceiling (#97). Notably removing the ortho-pyridine, but keeping a coordinating group, does not help (though pyridine substitution is OK). Folding into overall SAR: analysis by Dana #94.

• The green compounds have not been made, but would be useful as filling SAR holes.
• The yellow compounds are possibilities for building off existing promising compounds, or are obvious gaps. @drc007 mentioned the possibility of a dimethylamino on the pyridine (making the N more basic, and the compound maybe more soluble).
• Some previous saturated cores were explored (like OSA865), but with a poor other substituent. So we cannot really conclude much about those.
• N-alkylations involving heteroatoms in the chain (like OSA982) have not really been explored, but could be.
• Dana has summarised the needs at the bottom of #94.

2) New compounds from @danielgedder (homologous series) @QSimpson

If we assume next biological eval is late Oct. Then make the high priority tolyl compound (InChI=1S/C19H15N3/c1-14-8-10-15(11-9-14)19-18(16-6-2-4-12-20-16)21-17-7-3-5-13-22(17)19/h2-13H,1H3). Daniel can by then ship several homologated compounds.

There was a discussion on which compounds Quillon and @loriferrins may have available for synthesis/shipping (shown below). On exocyclic N, alkyl chains better than methyl, generally. There was interest in the "DMAP"-type compound (like the one suggested by @drc007) which is NEU-0006672, which would need N-aklylating (which would be a challenge!).

Residual Q: Which of the NEU compounds might we be able to source by later this month?

3) Alex final tox data - update in next meeting. 4) Any updates from Lee Graves re MoA. Mat has chased and is chasing. 5) Anything else hanging over from #89 e.g. could we please get rid of these?

• Manual strings are needed in LabArchives. If you sketch molecules in LA, the metadata is not Googleable. This needs fixing if we're going to continue to use LA on a large scale, since the metadata need to be automatic.

• Ensuring that commercial searching of compounds is installed in our workflow: @MFernflower to install something in the wiki to remind people of the need, in our day-to-day workflow, to search whether molecules are commercially available using resources like Enamine, MCule, Manifold.

• Google indexing of OSA molecules. Does not happen - sheets are not indexed. How do we solve, to ensure we're findable. Are open CDD sheets Googleable? Could try a SMILES search on a known, unique compound? @drc007 will look into this further with e.g. Datawarrior folks.

ACTIONS

• [x] @danaklug make high priority tolyl compound
• [ ] ALL: consider SAR holes identified in #94
• [ ] @danielgedder to ship compounds to London for eval at end of Oct.
• [ ] @QSimpson @loriferrins to finalise list of potentially useful compounds that could be shipped for eval at end of Oct
• [ ] @MFernflower to capture commercial searching in part of molecule procurement workflow in wiki here
• [ ] @QSimpson to see whether an open CDD sheet/vault is Googleable
• [ ] @drc007 to look into solutions for converting master list to something Googleable.

[MFernflower]

A possible matched pair talked about in the meeting

[mattodd]

Screengrabs of @QSimpson slides shown in meeting

[QSimpson]

OSA Oct 1st.pptx