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16th December 2014 @ 22:51
Which molecules to make next in Open Source Malaria Series 4? The full reasoning is below. The executive summary is that OSM needs these ten molecules: And if you'd like to synthesise them yourself (open source only please), or suggest better ones, you're free to do so. You can comment on this post below (easy login via Google), on Twitter, Github, G+ or email (opensourcemalaria at gmail).  1. Immediate Actions on the FrontrunnersSome good-looking compounds are known that possess chiral amine groups in the northwest, and some analogs are currently being synthesized in the lab: (note GHI=“Git Hub Issue”, e.g. GHI 242) Of interest here are:  i) whether the compound activity arises from one of the enantiomers,  ii) the metabolic profile of these compounds. Primary amines should be better than tertiary from the point of view of hERG and metabolic stability (the substitution of fluorophenyl for phenyl is for synthetic ease and won’t improve matters, but can be dealt with later), and  iii) whether the mono-methyl substituent (in MMV670763) really does obliterate activity (a surprising result given the surrounding compounds)Alice Williamson has said that the cyano substituent has caused solubility problems in the lab, so this will be changed to OCHF2, CF3 or Cl. Of these perhaps the most interesting compound will be the one containing the primary amine. So the immediate aim is to synthesize compounds A-C below racemic and enantiopure (using phenylglycine), to confirm activity and to check logD/clearance. The racemate could also be sent out to interested parties for a resolution. While the cLogP’s of these compounds are too high, the evaluation of these compounds has the other benefits of addressing the points above. Compounds D-F are of interest but secondary targets - these are available to synthesize by anyone, and would be tested as for A-C, and included in the first OSM Series 4 paper.For the compounds with ethers/alcohols in the benzylic position, again there are compounds in development and there are relevant knowns: The same comments apply about the cyano substituent generating solubility problems, so that will be changed in the compounds to be prioritized. The suitably altered alcohol (GHI235) and ether (GHI236) remain of interest, again with a view to separating enantiomers, most likely by HPLC using the services of a contributing lab. The exploration of alkyl substitution in the northwest is of interest, but the only known example of this substitution (MMV670762) was inactive. The compound with the dimethyl substitution will be prioritized, with the mono methyl as a backup. Hence these compounds can be added to the shortlist:   2. Parking the Amide Series For NowThe amide series possesses many active compounds, but recent data has suggested this series presents more of a hERG and Aldehyde Oxidase risk than the ether series, so will for the moment be parked. Relevant data: [blog=11081]Compounds sent for evaluation against the hERG ion channel at AstraZeneca[/blog] [blog=11208]Results of Series 4 Aldehyde Oxidase Assay[/blog] The amides have also demonstrated extreme sensitivity to substitution in the northwest aromatic ring, without a significant increase in the potency: [blog=11216]Evaluation of Latest Series 4 Analogs in Ether and Amide Series[/blog] The amide series is therefore a lower priority than the ether series at present. The relevant synthetic chemistry that was being developed by Tom (carbonylation) will be written up as a community opportunity for someone interested in a methodology project.3. Acting on the Aldehyde Oxidase DataThe data obtained from Pfizer: [blog=11208]Results of Series 4 Aldehyde Oxidase Assay[/blog] indicate that though AO activity is a risk for some members of the series, several potent compounds are not substrates. The inherited project data also show that simple blocking of the pyrazinyl ring reduce potency: (note also that likely metabolites are inactive:) Jamie Scott is making some analogs based on a triazolopyridine, (GHI 266 and 267) to see if the presence of the relevant ring nitrogen is important for potency, and this would allow testing in an AO assay: Given these findings, and Jamie's current efforts, there is low current need to modify the triazolopyrazine core further to try to reduce/investigate AO activity.4. Explore Changes in NortheastThe major synthetic focus is exploration of new substitution in the Northeast. What’s known about variation here is already on the wiki, but is repeated here, including some new more recent results. The para-substituent on the aromatic ring can be OCF3 or OCHF2 but seemingly not CH3:   Pyridyl has proven to be a poor choice, though there is a known potent compound with a substituted pyridine in this position, and clearly the pyridine helps lower logP: Aliphatic or other changes in the Northeast have to date proven to lower potency: Previous suggestions for analogs with variation in the Northeast include many suggestions from Alice in response to ESAC report [blog=10462]ESAC Report 2014[/blog] shown on GHI 261. Suggestions for interesting compounds to make in the next round are these: 5. Summary of Metabolic Data vs. Solubility vs. cLogPAn important To Do items is to create a spreadsheet of all the available metabolic, solubility and predicted solubility data for Series 4 (shown as pictures on the wiki) to check:i) impact of solubility on clearanceii) accuracy of cLogP predictions vs. realityThis is an open To Do item that will be actioned and posted separately, though the results may alter compound design. 6. The Shortlist Taking into account the above, and the need for a cLogP of less than 3, the 2014 Christmas Top 10 is as follows: If you'd like to contribute to OSM, you can i) Make these compounds yourself, or others on this page. You need to work in the open. ii) Suggest better compounds for the shortlist below (using a Google login) or on Twitter (@O_S_M), on Github or on Google+, or as a last resort (since it's not open) use email (opensourcemalaria at gmail) iii) Do some predictive modeling of these compounds to suggest metabolic liabilities they may possess. Happy holidays everyone!   (This post authored originally by Mat Todd. This content, as with all OSM content, is CC-BY) Strings for molecules mentioned in this postGHI242 CN(C)C(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C22H20N6O/c1-27(2)19(17-6-4-3-5-7-17)15-29-21-14-24-13-20-25-26-22(28(20)21)18-10-8-16(12-23)9-11-18/h3-11,13-14,19H,15H2,1-2H3 RQLWYQJRHWLJKI-UHFFFAOYSA-NGHI241 CNC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C21H18N6O/c1-23-18(16-5-3-2-4-6-16)14-28-20-13-24-12-19-25-26-21(27(19)20)17-9-7-15(11-22)8-10-17/h2-10,12-13,18,23H,14H2,1H3 FGPUCVLDQMTWKM-UHFFFAOYSA-NGHI240 NC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C20H16N6O/c21-10-14-6-8-16(9-7-14)20-25-24-18-11-23-12-19(26(18)20)27-13-17(22)15-4-2-1-3-5-15/h1-9,11-12,17H,13,22H2 RGOLJPNZJGCEBP-UHFFFAOYSA-NMMV670437 FC(C=C1)=C(F)C=C1C(N(C)C)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C22H19F4N5O2/c1-30(2)18(14-5-8-16(23)17(24)9-14)12-32-20-11-27-10-19-28-29-21(31(19)20)13-3-6-15(7-4-13)33-22(25)26/h3-11,18,22H,12H2,1-2H3 PMIWBIXSAYKRGF-UHFFFAOYSA-NMMV670763 FC(C=C1)=C(F)C=C1C(N([H])C)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C21H17F4N5O2/c1-26-17(13-4-7-15(22)16(23)8-13)11-31-19-10-27-9-18-28-29-20(30(18)19)12-2-5-14(6-3-12)32-21(24)25/h2-10,17,21,26H,11H2,1H3 YFUIAROYVNJDHR-UHFFFAOYSA-NMMV671651 FC(C=C1)=C(F)C=C1C(N([H])[H])COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C20H15F4N5O2/c21-14-6-3-12(7-15(14)22)16(25)10-30-18-9-26-8-17-27-28-19(29(17)18)11-1-4-13(5-2-11)31-20(23)24/h1-9,16,20H,10,25H2 BIGCWGPLTSPPFJ-UHFFFAOYSA-NCompound A: NC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C20H17F2N5O2/c21-20(22)29-15-8-6-14(7-9-15)19-26-25-17-10-24-11-18(27(17)19)28-12-16(23)13-4-2-1-3-5-13/h1-11,16,20H,12,23H2 APNVCAYADQJJBZ-UHFFFAOYSA-NCompound B: NC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)(F)F)C=C4)N32 InChI=1S/C20H16F3N5O2/c21-20(22,23)30-15-8-6-14(7-9-15)19-27-26-17-10-25-11-18(28(17)19)29-12-16(24)13-4-2-1-3-5-13/h1-11,16H,12,24H2 INWYDCAJFDBEMF-UHFFFAOYSA-NCompound C: ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(N)C4=CC=CC=C4)N32 InChI=1S/C19H16ClN5O/c20-15-8-6-14(7-9-15)19-24-23-17-10-22-11-18(25(17)19)26-12-16(21)13-4-2-1-3-5-13/h1-11,16H,12,21H2 DNSLEDXZUCYMEH-UHFFFAOYSA-NCompound D: CNC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C21H19F2N5O2/c1-24-17(14-5-3-2-4-6-14)13-29-19-12-25-11-18-26-27-20(28(18)19)15-7-9-16(10-8-15)30-21(22)23/h2-12,17,21,24H,13H2,1H3 NXAYCBUWEUBZHA-UHFFFAOYSA-NCompound E: CNC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)(F)F)C=C4)N32 InChI=1S/C21H18F3N5O2/c1-25-17(14-5-3-2-4-6-14)13-30-19-12-26-11-18-27-28-20(29(18)19)15-7-9-16(10-8-15)31-21(22,23)24/h2-12,17,25H,13H2,1H3 HGKAZGKLOVRNSC-UHFFFAOYSA-NCompound F: ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(NC)C4=CC=CC=C4)N32 InChI=1S/C20H18ClN5O/c1-22-17(14-5-3-2-4-6-14)13-27-19-12-23-11-18-24-25-20(26(18)19)15-7-9-16(21)10-8-15/h2-12,17,22H,13H2,1H3 MEBGOUOIJWXZQK-UHFFFAOYSA-NGHI235 OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C20H15N5O2/c21-10-14-6-8-16(9-7-14)20-24-23-18-11-22-12-19(25(18)20)27-13-17(26)15-4-2-1-3-5-15/h1-9,11-12,17,26H,13H2 DAFIYRWZRZBCCQ-UHFFFAOYSA-NGHI235 (Fluoro Analog) OC(C1=CC(F)=C(F)C=C1)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C20H13F2N5O2/c21-15-6-5-14(7-16(15)22)17(28)11-29-19-10-24-9-18-25-26-20(27(18)19)13-3-1-12(8-23)2-4-13/h1-7,9-10,17,28H,11H2 HHHWRCNBDNZMPN-UHFFFAOYSA-NGHI236 COC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C21H17N5O2/c1-27-18(16-5-3-2-4-6-16)14-28-20-13-23-12-19-24-25-21(26(19)20)17-9-7-15(11-22)8-10-17/h2-10,12-13,18H,14H2,1H3 QAGSTSUWCMAMBB-UHFFFAOYSA-NGHI239 CC(OC)COC1=CN=CC2=NN=C(C3=CC=C(C#N)C=C3)N21 InChI=1S/C16H15N5O2/c1-11(22-2)10-23-15-9-18-8-14-19-20-16(21(14)15)13-5-3-12(7-17)4-6-13/h3-6,8-9,11H,10H2,1-2H3 PDPLSDFAIQBTIZ-UHFFFAOYSA-NGHI238 COC(C)(C)COC1=CN=CC2=NN=C(C3=CC=C(C#N)C=C3)N21 InChI=1S/C17H17N5O2/c1-17(2,23-3)11-24-15-10-19-9-14-20-21-16(22(14)15)13-6-4-12(8-18)5-7-13/h4-7,9-10H,11H2,1-3H3 QCZSLJNWYVZRRV-UHFFFAOYSA-NMMV672723 FC(C=C1)=C(F)C=C1C(O)(C)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C21H16F4N4O3/c1-21(30,13-4-7-15(22)16(23)8-13)11-31-18-10-26-9-17-27-28-19(29(17)18)12-2-5-14(6-3-12)32-20(24)25/h2-10,20,30H,11H2,1H3 NBSLUXDUMZFLCA-UHFFFAOYSA-NMMV672687 FC(C=C1)=C(F)C=C1C(O)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C20H14F4N4O3/c21-14-6-3-12(7-15(14)22)16(29)10-30-18-9-25-8-17-26-27-19(28(17)18)11-1-4-13(5-2-11)31-20(23)24/h1-9,16,20,29H,10H2 BXEWPSCIVPVASC-UHFFFAOYSA-NMMV670762 FC(OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(F)(F)F)N32)F InChI=1S/C14H9F5N4O2/c15-13(16)25-9-3-1-8(2-4-9)12-22-21-10-5-20-6-11(23(10)12)24-7-14(17,18)19/h1-6,13H,7H2 VZIMTSNALAAOKI-UHFFFAOYSA-NCompound G: OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C20H16F2N4O3/c21-20(22)29-15-8-6-14(7-9-15)19-25-24-17-10-23-11-18(26(17)19)28-12-16(27)13-4-2-1-3-5-13/h1-11,16,20,27H,12H2 GEHCMLKWLSBHDX-UHFFFAOYSA-NCompound H: OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)(F)F)C=C4)N32 InChI=1S/C20H15F3N4O3/c21-20(22,23)30-15-8-6-14(7-9-15)19-26-25-17-10-24-11-18(27(17)19)29-12-16(28)13-4-2-1-3-5-13/h1-11,16,28H,12H2 ZBQZXWIEUVKEGD-UHFFFAOYSA-NCompound I: ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(O)C4=CC=CC=C4)N32 InChI=1S/C19H15ClN4O2/c20-15-8-6-14(7-9-15)19-23-22-17-10-21-11-18(24(17)19)26-12-16(25)13-4-2-1-3-5-13/h1-11,16,25H,12H2 KDXBMCNZHBPMID-UHFFFAOYSA-NCompound J: COC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C21H18F2N4O3/c1-28-17(14-5-3-2-4-6-14)13-29-19-12-24-11-18-25-26-20(27(18)19)15-7-9-16(10-8-15)30-21(22)23/h2-12,17,21H,13H2,1H3 YDHUWNKEIONDLX-UHFFFAOYSA-NCompound K: COC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)(F)F)C=C4)N32 InChI=1S/C21H17F3N4O3/c1-29-17(14-5-3-2-4-6-14)13-30-19-12-25-11-18-26-27-20(28(18)19)15-7-9-16(10-8-15)31-21(22,23)24/h2-12,17H,13H2,1H3 XZNMMEOLACDFOM-UHFFFAOYSA-NCompound L: ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(OC)C4=CC=CC=C4)N32 InChI=1S/C20H17ClN4O2/c1-26-17(14-5-3-2-4-6-14)13-27-19-12-22-11-18-23-24-20(25(18)19)15-7-9-16(21)10-8-15/h2-12,17H,13H2,1H3 FJXGOWUTCAFUKB-UHFFFAOYSA-NCompound M: COC(C)(C)COC1=CN=CC2=NN=C(C3=CC=C(OC(F)F)C=C3)N21 InChI=1S/C17H18F2N4O3/c1-17(2,24-3)10-25-14-9-20-8-13-21-22-15(23(13)14)11-4-6-12(7-5-11)26-16(18)19/h4-9,16H,10H2,1-3H3 QPGDQEMNKJULOO-UHFFFAOYSA-NCompound N: COC(C)(C)COC1=CN=CC2=NN=C(C3=CC=C(OC(F)(F)F)C=C3)N21 InChI=1S/C17H17F3N4O3/c1-16(2,25-3)10-26-14-9-21-8-13-22-23-15(24(13)14)11-4-6-12(7-5-11)27-17(18,19)20/h4-9H,10H2,1-3H3 JLRZYQRSTMYUNL-UHFFFAOYSA-NCompound O: ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(C)(C)OC)N32 InChI=1S/C16H17ClN4O2/c1-16(2,22-3)10-23-14-9-18-8-13-19-20-15(21(13)14)11-4-6-12(17)7-5-11/h4-9H,10H2,1-3H3 CSHXFYLIRDWKAB-UHFFFAOYSA-NCompound P: COC(C)COC1=CN=CC2=NN=C(C3=CC=C(OC(F)F)C=C3)N21 InChI=1S/C16H16F2N4O3/c1-10(23-2)9-24-14-8-19-7-13-20-21-15(22(13)14)11-3-5-12(6-4-11)25-16(17)18/h3-8,10,16H,9H2,1-2H3 JOIANTFQDWQBSI-UHFFFAOYSA-NCompound Q: COC(C)COC1=CN=CC2=NN=C(C3=CC=C(OC(F)(F)F)C=C3)N21 InChI=1S/C16H15F3N4O3/c1-10(24-2)9-25-14-8-20-7-13-21-22-15(23(13)14)11-3-5-12(6-4-11)26-16(17,18)19/h3-8,10H,9H2,1-2H3 KMHXMKGJDPCJNH-UHFFFAOYSA-NCompound R: ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(C)OC)N32 InChI=1S/C15H15ClN4O2/c1-10(21-2)9-22-14-8-17-7-13-18-19-15(20(13)14)11-3-5-12(16)6-4-11/h3-8,10H,9H2,1-2H3 PCMAXZRFAMSVAN-UHFFFAOYSA-N MMV668823 FC1=C(F)C=CC(CCOC2=CN=C(Cl)C3=NN=C(C4=CC=C(OC(F)F)C=C4)N32)=C1 InChI=1S/C20H13ClF4N4O2/c21-17-19-28-27-18(12-2-4-13(5-3-12)31-20(24)25)29(19)16(10-26-17)30-8-7-11-1-6-14(22)15(23)9-11/h1-6,9-10,20H,7-8H2 FOQQXRIKYKUBGB-UHFFFAOYSA-N MMV669102 FC1=C(F)C=CC(CCOC2=CN=C(N(CC)CC)C3=NN=C(C4=CC=C(OC(F)F)C=C4)N32)=C1 InChI=1S/C24H23F4N5O2/c1-3-32(4-2)22-23-31-30-21(16-6-8-17(9-7-16)35-24(27)28)33(23)20(14-29-22)34-12-11-15-5-10-18(25)19(26)13-15/h5-10,13-14,24H,3-4,11-12H2,1-2H3 XEJMUSAAKCRDEX-UHFFFAOYSA-N MMV669541 FC1=C(F)C=CC(CCOC2=CN=C(C)C3=NN=C(C4=CC=C(OC(F)F)C=C4)N32)=C1 InChI=1S/C21H16F4N4O2/c1-12-19-27-28-20(14-3-5-15(6-4-14)31-21(24)25)29(19)18(11-26-12)30-9-8-13-2-7-16(22)17(23)10-13/h2-7,10-11,21H,8-9H2,1H3 ZOSZOZWECBRIDQ-UHFFFAOYSA-N MMV669311 FC1=C(F)C=CC(CCOC2=CN=C(N)C3=NN=C(C4=CC=C(OC(F)F)C=C4)N32)=C1 InChI=1S/C20H15F4N5O2/c21-14-6-1-11(9-15(14)22)7-8-30-16-10-26-17(25)19-28-27-18(29(16)19)12-2-4-13(5-3-12)31-20(23)24/h1-6,9-10,20H,7-8H2,(H2,25,26) XAQYLJFKZCILRM-UHFFFAOYSA-N MMV675960 FC1=C(F)C=CC(CCOC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32)=C1 InChI=1S/C20H14F4N4O2/c21-15-6-1-12(9-16(15)22)7-8-29-18-11-25-10-17-26-27-19(28(17)18)13-2-4-14(5-3-13)30-20(23)24/h1-6,9-11,20H,7-8H2 DEEWBVYNQGALDU-UHFFFAOYSA-N MMV669025 FC1=C(F)C=CC(CCOC2=CNC(C3=NN=C(C4=CC=C(OC(F)F)C=C4)N32)=O)=C1 InChI=1S/C20H14F4N4O3/c21-14-6-1-11(9-15(14)22)7-8-30-16-10-25-19(29)18-27-26-17(28(16)18)12-2-4-13(5-3-12)31-20(23)24/h1-6,9-10,20H,7-8H2,(H,25,29) ZXMYJCVYBZFJIJ-UHFFFAOYSA-N MMV668822 FC1=C(F)C=CC(CCOC2=C[N+]([O-])=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32)=C1 InChI=1S/C20H14F4N4O3/c21-15-6-1-12(9-16(15)22)7-8-30-18-11-27(29)10-17-25-26-19(28(17)18)13-2-4-14(5-3-13)31-20(23)24/h1-6,9-11,20H,7-8H2 CUNPWKYJVCNHNZ-UHFFFAOYSA-N Jamie1: ClC1=CC=CC=C1CCOC2=CC=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C21H15ClN4O/c22-18-5-2-1-4-16(18)12-13-27-20-7-3-6-19-24-25-21(26(19)20)17-10-8-15(14-23)9-11-17/h1-11H,12-13H2 APTFJFHOJWNXBX-UHFFFAOYSA-N Jamie 2: O=C(NC1=CC(Cl)=CC=C1)C2=CC=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C20H13ClF2N4O2/c21-13-3-1-4-14(11-13)24-19(28)16-5-2-6-17-25-26-18(27(16)17)12-7-9-15(10-8-12)29-20(22)23/h1-11,20H,(H,24,28) NVCZJGCEAVJDRA-UHFFFAOYSA-N Jamie 3: O=C(NC1=CC(C(F)(F)F)=NC=C1)C2=CC=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C20H11F3N6O/c21-20(22,23)16-10-14(8-9-25-16)26-19(30)15-2-1-3-17-27-28-18(29(15)17)13-6-4-12(11-24)5-7-13/h1-10H,(H,25,26,30) PGPJMFWOQCDCCV-UHFFFAOYSA-N MMV675947 OSM-S-254 O=C(NC1=CC(Cl)=CC=C1C)C2=CN=CC(N23)=NN=C3C4=CC=C(OC(F)F)C=C4 InChI=1S/C20H14ClF2N5O2/c1-11-2-5-13(21)8-15(11)25-19(29)16-9-24-10-17-26-27-18(28(16)17)12-3-6-14(7-4-12)30-20(22)23/h2-10,20H,1H3,(H,25,29) QKXZFYOMVFGRGS-UHFFFAOYSA-N MMV675952 OSM-S-257 O=C(NC1=CC(Cl)=CC=C1C)C2=CN=CC(N23)=NN=C3C4=CC=C(OC)C=C4 InChI=1S/C20H16ClN5O2/c1-12-3-6-14(21)9-16(12)23-20(27)17-10-22-11-18-24-25-19(26(17)18)13-4-7-15(28-2)8-5-13/h3-11H,1-2H3,(H,23,27) NFXWTMUWMZSIFL-UHFFFAOYSA-N MMV675946 OSM-S-204 O=C(NC1=C(F)C(Cl)=CC=C1)C2=CN=CC(N23)=NN=C3C4=CC=C(OC(F)F)C=C4 InChI=1S/C19H11ClF3N5O2/c20-12-2-1-3-13(16(12)21)25-18(29)14-8-24-9-15-26-27-17(28(14)15)10-4-6-11(7-5-10)30-19(22)23/h1-9,19H,(H,25,29) WBRLFZGDBUVKSB-UHFFFAOYSA-N MMV675951 OSM-S-256 O=C(NC1=C(F)C(Cl)=CC=C1)C2=CN=CC(N23)=NN=C3C4=CC=C(OC)C=C4 InChI=1S/C19H13ClFN5O2/c1-28-12-7-5-11(6-8-12)18-25-24-16-10-22-9-15(26(16)18)19(27)23-14-4-2-3-13(20)17(14)21/h2-10H,1H3,(H,23,27) FWGBPGUTIFKBOZ-UHFFFAOYSA-N MMV675963 OSM-S-271 O=C(NC1=CC(Cl)=CC=C1)C2=CN=CC(N23)=NN=C3C4=CC=C(OC(F)(F)F)C=C4 InChI=1S/C19H11ClF3N5O2/c20-12-2-1-3-13(8-12)25-18(29)15-9-24-10-16-26-27-17(28(15)16)11-4-6-14(7-5-11)30-19(21,22)23/h1-10H,(H,25,29) KPPYAXXEDYTONY-UHFFFAOYSA-N MMV669542 OSM-S-202 O=C(NC1=CC(Cl)=CC=C1)C2=CN=CC(N23)=NN=C3C4=CC=C(OC(F)F)C=C4 InChI=1S/C19H12ClF2N5O2/c20-12-2-1-3-13(8-12)24-18(28)15-9-23-10-16-25-26-17(27(15)16)11-4-6-14(7-5-11)29-19(21)22/h1-10,19H,(H,24,28) AJGOFYWOTIIYLR-UHFFFAOYSA-N OSM-S-201 O=C(NC1=C(C)C(Cl)=CC=C1)C2=CN=CC(N23)=NN=C3C4=CC=C(OC(F)F)C=C4 InChI=1S/C20H14ClF2N5O2/c1-11-14(21)3-2-4-15(11)25-19(29)16-9-24-10-17-26-27-18(28(16)17)12-5-7-13(8-6-12)30-20(22)23/h2-10,20H,1H3,(H,25,29) IVENWLQUYSRINV-UHFFFAOYSA-N MMV675950 OSM-S-255 O=C(NC1=C(C)C(Cl)=CC=C1)C2=CN=CC(N23)=NN=C3C4=CC=C(OC)C=C4 InChI=1S/C20H16ClN5O2/c1-12-15(21)4-3-5-16(12)23-20(27)17-10-22-11-18-24-25-19(26(17)18)13-6-8-14(28-2)9-7-13/h3-11H,1-2H3,(H,23,27) LIAWHOKMZQICES-UHFFFAOYSA-N Compound S: OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4CCCCC4)N32 InChI=1S/C19H22N4O2/c24-16(14-7-3-1-4-8-14)13-25-18-12-20-11-17-21-22-19(23(17)18)15-9-5-2-6-10-15/h1,3-4,7-8,11-12,15-16,24H,2,5-6,9-10,13H2 LWDWZIVAQMSZHL-UHFFFAOYSA-N Compound T: OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=CC=C4)N32 InChI=1S/C19H16N4O2/c24-16(14-7-3-1-4-8-14)13-25-18-12-20-11-17-21-22-19(23(17)18)15-9-5-2-6-10-15/h1-12,16,24H,13H2 HQWUAOFYEUBLBZ-UHFFFAOYSA-N Compound U: OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4COC4)N32 InChI=1S/C16H16N4O3/c21-13(11-4-2-1-3-5-11)10-23-15-7-17-6-14-18-19-16(20(14)15)12-8-22-9-12/h1-7,12-13,21H,8-10H2 ZLHKTQHFEDMDIZ-UHFFFAOYSA-N Compound V: OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CN=C(C(F)(F)F)C=C4)N32 InChI=1S/C19H14F3N5O2/c20-19(21,22)15-7-6-13(8-24-15)18-26-25-16-9-23-10-17(27(16)18)29-11-14(28)12-4-2-1-3-5-12/h1-10,14,28H,11H2 YUTTVQUFLHMVCQ-UHFFFAOYSA-N Compound W: OC(C1=CC=CC=C1)COC2=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 Compound X: OC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(CC)N32 InChI=1S/C15H16N4O2/c1-2-13-17-18-14-8-16-9-15(19(13)14)21-10-12(20)11-6-4-3-5-7-11/h3-9,12,20H,2,10H2,1H3 ZMELTVBBQIUHNR-UHFFFAOYSA-N      
Attached Files
Benzylic amines underway.png
Benzylic amines underway.cdxml
Top 10 Amines.png
Top 10 Amines.cdxml
Ethers Underway.cdxml
Ethers Underway.png
Top 10 Ethers.cdxml
Top 10 Ethers.png
Lactams.cdx
Pyrazine_Substitution_Mods.png
Lactams.png
Pyrazine Substitution Mods.cdx
CH3 vs CHF2 vs CF3 Northeast.cdxml
Aromatic Variants in Northeast.cdxml
Cycloaliphatic Triazole Subst v3.cdx
Aromatic Variants in Northeast.png
CH3 vs CHF2 vs CF3 Northeast.png
Cycloaliphatic Triazole Subst v3.png
Northeast Shortlist.cdxml
Northeast Shortlist.png
Jamie Scott Targets.cdxml
Jamie Scott Targets.png
Christmas Top 10.cdxml
Christmas Top 10.png