Next batch of compounds sent for testing April and June 2024

[qxsml]

These nine Series 4 compounds (synthesized at University College London) have been tested for activity (at https://github.com/OpenSourceMalaria/Series4_PredictiveModel/issues/34). Please find the details below:

OSM-LO-92; MMV897697-02；SMILES: FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CC=CC=C4)N32

OSM-LO-93; MMV2323731-01; SMILES: FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(OC)C4=CC=CC=C4)N32

OSM-LO-94; MMV2323732-01; SMILES: FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC=CC(N+=O)=C4)N32

OSM-LO-95; MMV2323733-01; SMILES: FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CC=CC(Br)=C4)N32

OSM-LO-96; MMV2323734-01; SMILES: FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=C(F)C=CC=C4F)N32

OSM-LO-97; MMV2323735-01; SMILES: FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CC5=C(C=C4)OCO5)N32

OSM-LO-98; MMV2323736-01; SMILES: FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=NC=CC(OC(F)F)=C4)N32

OSM-LO-99; MMV2323737-01; SMILES: FC(F)OC1=CC=C(C=C1)C2=NN=C3C=NC=C(OCC4=C(C(F)(F)F)C=CN=C4)N32

OSM-LO-100; MMV2323738-01; SMILES: FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCCC(F)(F)F)N32

[edwintse]

@qxsml Looks good! Just in terms of colour coding the potencies, we have normally done <1.0 µM = green, 1.0–2.5 µM = orange, >2.5 µM = red. That way everything is consistent across all the compounds.

[qxsml]

@qxsml Looks good! Just in terms of colour coding the potencies, we have normally done <1.0 µM = green, 1.0–2.5 µM = orange, >2.5 µM = red. That way everything is consistent across all the compounds.

Hi Edwin, thank you very much for letting me know！ I corrected it.

[MFernflower]

I know it is only n of 1 but really cool how you can just delete a phenyl ring and it still works !!!

Message ID: @.***>

[mattodd]

Yes, OSM-LO-100 is the big news item here. Any docking model needs to account for that!

[MFernflower]

SMILE strings of my proposed molecules @mattodd

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCCC(F)([H])F)N32

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCCC(F)([H])[H])N32

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCCC([H])([H])[H])N32

@edwintse

[miquelduranfrigola]

These results are interesting and I agree with @mattodd and @MFernflower that OSM-LO-100 is the big news here. Below, see structures suggested by @MFernflower in the previous comment

As for docking - @mattodd: do you know if someone can have a look into it? That would certainly be an interesting thing to check.

[GemmaTuron]

Hi @qxsml

Why did we end up doing Target 18 instead of Target 27? According to the colour-code in issue 34 we marked 27 in blue whereas 18 was not that easy

Thanks!

[qxsml]

Hi @qxsml

Why did we end up doing Target 18 instead of Target 27? According to the colour-code in issue 34 we marked 27 in blue whereas 18 was not that easy

Thanks!

Hi Gemma,

I had trouble making Target 27. The compound I isolated was a mixture of two. I purified this compound to 90% (LCMS) recently, and shipped it for testing last week.

Xin

[GemmaTuron]

Thanks for the update @qxsml

[qxsml]

OSM-LO-123; MMV2324976; FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CNC5=C4C=CC=C5)N32 OSM-LO-124; MMV2324977; FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCCC([H])([H])[H])N32 OSM-LO-125; MMV2324978; FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCCC([H])([H])F)N32 OSM-LO-126; MMV2324979; FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCCCC(F)(F)F)N32 OSM-LO-127; MMV2324980; FC(F)(F)CCOC1=CN=CC2=NN=C(C3=CC=C(OC(F)F)C=C3)N21

[mattodd]

Jeez, really interesting @qxsml. The potencies track very smoothly with chain length and F content... We must work with the ANU team to figure out how these might be binding to the protein. Have reached out by email. Just for interest, could we easily access the CF3-hexanol..? Can we get the pentanol with more F's on it?

[miquelduranfrigola]

That is so interesting. Thanks @qxsml

[MFernflower]

@mattodd some halogenated fatty alcohols are available but are $$$

https://www.ambeed.com/products/1535364-59-0.html

On Fri, Jun 14, 2024, 12:03 PM Miquel Duran-Frigola < @.***> wrote:

That is so interesting. Thanks @qxsml https://github.com/qxsml

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[MFernflower]

@mattodd 2-Chloroethyl ethyl ether seems to be commercially available and not too pricy however - maybe a PEG chain will work as well as the halogenated fatty chain?

On Fri, Jun 14, 2024, 12:08 PM MFernflower @.***> wrote:

@mattodd some halogenated fatty alcohols are available but are $$$

https://www.ambeed.com/products/1535364-59-0.html

On Fri, Jun 14, 2024, 12:03 PM Miquel Duran-Frigola < @.***> wrote:

That is so interesting. Thanks @qxsml https://github.com/qxsml

— Reply to this email directly, view it on GitHub https://github.com/OpenSourceMalaria/Series4/issues/79#issuecomment-2168329923, or unsubscribe https://github.com/notifications/unsubscribe-auth/AAYEWDTJEOTCYMCH4IX6QTLZHMH6BAVCNFSM6AAAAABG24LE2WVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMZDCNRYGMZDSOJSGM . You are receiving this because you were mentioned.Message ID: @.***>

[MFernflower]

@mattodd @miquelduranfrigola @qxsml

Here is my idea - the two alkyl chlorides needed can be bought cheaply from suppliers e.g

https://www.ambeed.com/products/69749-71-9.html https://www.ambeed.com/products/628-34-2.html