Desirable Compounds Not Yet Synthesised
This part of the wiki tracks suggestions of molecules that have yet to be completed. To suggest a molecule, it's best to start an Issue (tab above; use the tag "Molecule Suggestion") so that the suggestion can be explained/justified/debated. If the suggestion is good, the molecule can be added below, the original Issue can be linked and the Issue can be closed.
(Synthetic planning from Nov 2015 can be seen here)
Side chain derived from phenylalanine: GHI 254, ELN, OSM-S-261
ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCH(N)CC4=CC=CC=C4)N32 InChI=1S/C20H18ClN5O/c21-16-8-6-15(7-9-16)20-25-24-18-11-23-12-19(26(18)20)27-13-17(22)10-14-4-2-1-3-5-14/h1-9,11-12,17H,10,13,22H2/t17-/m1/s1
The Tianyi compound (contains methylated imidazopyrazine core, analogous to MMV669846): Discussion of Desirability: GHI358, GHI390 Haverford Planning OC(C1=CC=CC=C1)COC2=CN=CC3=NC(C)=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C22H19F2N3O3/c1-14-21(16-7-9-17(10-8-16)30-22(23)24)27-19(26-14)11-25-12-20(27)29-13-18(28)15-5-3-2-4-6-15/h2-12,18,22,28H,13H2,1H3 VGNPLLBRBOUQAA-UHFFFAOYSA-N
The Heterooxazole (unexplored amide isostere in side chain): General discussion of the idea, Proposed synthesis, start of the synthesis, ELN FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(C4=CN=C(C5=CC=CC=C5)O4)N32 (free acid) InChI=1S/C21H13F2N5O2/c22-21(23)29-15-8-6-13(7-9-15)19-27-26-18-12-24-10-16(28(18)19)17-11-25-20(30-17)14-4-2-1-3-5-14/h1-12,21H FBTBZFMQUBZDSN-UHFFFAOYSA-N
The Heterooxadiazole (unexplored amide isostere in side chain): General discussion of the idea, Rationale, Proposed synthesis, Synthesis progress report by Haverford College, Relevant ELN, Revised synthetic route(s), Problems with imine formation, Discussion of potentially anomalous NMR spectrum, Second phase introduction and new ELN FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(C4=NC(C5=CC=CC=C5)=NO4)N32 InChI=1S/C20H12F2N6O2/c21-20(22)29-14-8-6-13(7-9-14)18-26-25-16-11-23-10-15(28(16)18)19-24-17(27-30-19)12-4-2-1-3-5-12/h1-11,20H HFPKPTYSFARKAA-UHFFFAOYSA-N
The hERG Evador/Acid Test (carboxylic acid analogue of MMV688896): Comment on desirability, Synthesis proposal, First synthesis attempt, summary and suggestions of ways forward with ELN, Discussion of synthetic roadblock, Discussion of Rationale. FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(C(O)=O)C4=CC=CC=C4)N32 InChI=1S/C21H16F2N4O4/c22-21(23)31-15-8-6-14(7-9-15)19-26-25-17-10-24-11-18(27(17)19)30-12-16(20(28)29)13-4-2-1-3-5-13/h1-11,16,21H,12H2,(H,28,29) FICNFVPYGUTYFV-UHFFFAOYSA-N
The Alkyl (Test to see if heteroatoms are needed on left-hand-side). Length may need tweaking - MMV669304 is potent): 1st proposed synthesis with commencement and ELN, 2nd proposed synthesis with ELN, FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(CCC4=CC=CC=C4)N32 InChI=1S/C20H16F2N4O/c21-20(22)27-17-10-7-15(8-11-17)19-25-24-18-13-23-12-16(26(18)19)9-6-14-4-2-1-3-5-14/h1-5,7-8,10-13,20H,6,9H2 QKTHSIJWBSHMDZ-UHFFFAOYSA-N
The Internal Alkyne (related to alkyl): Opening synthesis, ELN, discussion of rationale FC(F)OC1=CC=C(C2=NN=C3C=NC=C(C#CC4=CC=CC=C4)N32)C=C1 InChI=1S/C20H12F2N4O/c21-20(22)27-17-10-7-15(8-11-17)19-25-24-18-13-23-12-16(26(18)19)9-6-14-4-2-1-3-5-14/h1-5,7-8,10-13,20H KNVACGGMAGPRRW-UHFFFAOYSA-N
The Internal Alkene/Reduced Alkyl (synthetically related to alkyne and alkyl compounds; discussion of rationale of all three; The SMILES string is only for the cis isomer: Discussed, starting synthesis, Discussion of NMR spectrum of intermediate, ELN FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(/C=C\C4=CC=CC=C4)N32 InChI=1S/C20H14F2N4O/c21-20(22)27-17-10-7-15(8-11-17)19-25-24-18-13-23-12-16(26(18)19)9-6-14-4-2-1-3-5-14/h1-13,20H/b9-6- SGPCUHISMIPDDU-TWGQIWQCSA-N
The 6 (probe of tolerance to ring substitution): Synthesis proposal, Start of synthesis, ELN. Second phase Haverford attempt with second ELN FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC(C)=C(OCC(O)C4=CC=CC=C4)N32 InChI=1S/C21H18F2N4O3/c1-13-20(29-12-17(28)14-5-3-2-4-6-14)27-18(11-24-13)25-26-19(27)15-7-9-16(10-8-15)30-21(22)23/h2-11,17,21,28H,12H2,1H3 ZYFKQWHTACKGJR-UHFFFAOYSA-N
The 8 (also a probe of tolerance to ring substitution): Haverford synthesis plan, Start of Haverford synthesis, ELN, Rationale, Summary and closure of first attempt, cross-link to new attempt at 6- and 8- FC(F)OC(C=C1)=CC=C1C2=NN=C3C(C)=NC=C(OCC(O)C4=CC=CC=C4)N32 InChI=1S/C21H18F2N4O3/c1-13-19-25-26-20(15-7-9-16(10-8-15)30-21(22)23)27(19)18(11-24-13)29-12-17(28)14-5-3-2-4-6-14/h2-11,17,21,28H,12H2,1H3 ASWYMQOLUDKKDJ-UHFFFAOYSA-N
The Burns (amide isostere): Proposed synthesis from Haverford College, Start of synthesis, Discussion of results of intermediate steps here and here, ELN including summary of outcomes of first attempt. Start of Second Attempt with new ELN. FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(C(C(F)(F)F)NCC4=CC=CC=C4)N32 InChI=1S/C21H16F5N5O/c22-20(23)32-15-8-6-14(7-9-15)19-30-29-17-12-27-11-16(31(17)19)18(21(24,25)26)28-10-13-4-2-1-3-5-13/h1-9,11-12,18,20,28H,10H2 NYRGMZUFRGWPBF-UHFFFAOYSA-N
The Nemesis (deplanarisation of right-hand-side): Haverford College synthetic plan, Start of first Haverford synthesis, ELN, Second phase of synthesis with same ELN. OC(C1=CC=CC=C1)C OC2=CN=CC3=NN=C(C4CNCCC4)N32 InChI=1S/C18H21N5O2/c24-15(13-5-2-1-3-6-13)12-25-17-11-20-10-16-21-22-18(23(16)17)14-7-4-8-19-9-14/h1-3,5-6,10-11,14-15,19,24H,4,7-9,12H2 SNDLBGDEOQPBOQ-UHFFFAOYSA-N
The Ketone (analog of amide linker): Haverford College proposed syntheses, Start of synthesis, ELN. Also "ketone linker" folder in Ed Tse's lab notebook. Second Haverford College campaign with new ELN. FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(C(CC4=CC=CC=C4)=O)N32 InChI=1S/C20H14F2N4O2/c21-20(22)28-15-8-6-14(7-9-15)19-25-24-18-12-23-11-16(26(18)19)17(27)10-13-4-2-1-3-5-13/h1-9,11-12,20H,10H2 KALFSUSYOZTBSP-UHFFFAOYSA-N
The Urea was suggested here. ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(NC(NC4=CC=CC=C4)=O)N32 InChI=1S/C18H13ClN6O/c19-13-8-6-12(7-9-13)17-24-23-16-11-20-10-15(25(16)17)22-18(26)21-14-4-2-1-3-5-14/h1-11H,(H2,21,22,26) MNPRTDCYYNHGPG-UHFFFAOYSA-N
The Chase Difluorobenzamide was suggested as a result of the SAR associated with related "reversed amide" compounds. O=C(C1=CC(F)=C(F)C=C1)NC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C19H10F2N6O/c20-14-6-5-13(7-15(14)21)19(28)24-16-9-23-10-17-25-26-18(27(16)17)12-3-1-11(8-22)2-4-12/h1-7,9-10H,(H,24,28) IAUQUTZYIOSAOR-UHFFFAOYSA-N
The Dimethyl proposed synthesis from Haverford College. FC(F)OC(C=C1)=CC=C1C2=NN=C3C(C)=NC(C)=C(OCC(O)C4=CC=CC=C4)N32 InChI=1S/C22H20F2N4O3/c1-13-19-26-27-20(16-8-10-17(11-9-16)31-22(23)24)28(19)21(14(2)25-13)30-12-18(29)15-6-4-3-5-7-15/h3-11,18,22,29H,12H2,1-2H3 SPPBNNNUJINLLF-UHFFFAOYSA-N
The Chase Hop1 was suggested here. ClC(C=C1)=CC=C1C2=NN=NN2C3=CN=CC(OCCC4=CC(F)=C(F)C=C4)=N3 InChI=1S/C19H13ClF2N6O/c20-14-4-2-13(3-5-14)19-25-26-27-28(19)17-10-23-11-18(24-17)29-8-7-12-1-6-15(21)16(22)9-12/h1-6,9-11H,7-8H2 HHZUPBCYYAXEQO-UHFFFAOYSA-N
