Quick update on the compounds I've made and those I'm making

[edwintse]

Alongside some of the frontrunner resynthesis (#400), I have also been working on some other compounds for the next batch of samples to send to Syngene. (Note: CLogP values were calculated using DataWarrior (#385))

Compounds ready to ship (green box)

• OSM-S-363, -364 and -365 were synthesised as part of the hypothetical compounds (OSM Series 4 - Next Round of Synthesis #358) in addition to those already synthesised and evaluated (Compounds Shipped to Syngene May 2016 #384). These serve as a better comparison to the previous thioether compound (mentioned in Synthesis of 5-(benzylthio)-3-(4-(difluoromethoxy)phenyl)-[1,2,4]triazolo[4,3-a]pyrazine #377). OSM-S-368 and -369 were also synthesised to provide direct comparison with the two thioether compounds.
• OSM-S-370, -371 and -375 were synthesised following the discussion of using cubane bioisosteres (Cubane? #379). The three cubanes were generously provided by Craig Williams at UQ.
• OSM-S-372, -373 and -374 were synthesised as a suggestion following the potency discussion at the last online meeting (Meeting Discussion Point 3: Potency #390).

Compounds in progress (orange box)
(from left to right)

• As an amide comparison with OSM-S-375 above
• In order to prevent potential inherent cytotoxicity of OSM-S-374
• To reduce size of the substituent on the triazole
• As a comparison with OSM-S-373
• The azide is at hand and the compound may lower the CLogP

SMILES
(from left to right, top to bottom)

• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(SCCC4=CC=CC=C4)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(S(CCC4=CC=CC=C4)=O)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(S(CCC4=CC=CC=C4)(=O)=O)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CC=CC=C4)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC=CC=C4)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCCC45C6C7C4C8C5C6C87)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC45C6C7C4C8C5C6C78)N32
• IC12C(C3C1C4C52)C5C34C6=NN=C7C=NC=C(OCCC8=CC(F)=C(F)C=C8)N76
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CN(CC5=CC=CC=C5)N=N4)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CN(C5=CC=CC=C5)N=N4)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CN(C5=NC(Cl)=CN=C5)N=N4)N32
• IC12C(C3C1C4C52)C5C34C6=NN=C7C=NC=C(C(NC8=CC=NC(C(F)(F)F)=C8)=O)N76
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CN(C5=NC(OC)=CN=C5)N=N4)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CN(C(C)(C)C)N=N4)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CN(C5=NC=CC=C5)N=N4)N32
• FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CN(S(C5=CC=C(NC(C)=O)C=C5)(=O)=O)N=N4)N32

[edwintse]

Potency data for the final set of compounds has been written up here.