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28th November 2017 @ 01:00

A set of 26 Series 4 Triazolopyrazine compounds were sent to have their efficacy evaluated against Plasmodium flaciparum in-vitro at Dundee (GitHub issue #8)

The data has been posted here

Strings:

MMV Number SMILES InChI InChI Key
MMV1576784 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC/C4=C/BBBBBBBBBB4)N32 InChI=1S/C16H22B10F2N4O2/c27-16(28)34-12-3-1-10(2-4-12)15-31-30-13-8-29-9-14(32(13)15)33-6-5-11-7-17-19-21-23-25-26-24-22-20-18-11/h1-4,7-9,16-26H,5-6H2/b11-7- AGPVLTOPROUGPQ-XFFZJAGNSA-N
MMV1576785 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(N4CCOCC4)C5=CC=CC=C5)N32 InChI=1S/C24H23F2N5O3/c25-24(26)34-19-8-6-18(7-9-19)23-29-28-21-14-27-15-22(31(21)23)33-16-20(17-4-2-1-3-5-17)30-10-12-32-13-11-30/h1-9,14-15,20,24H,10-13,16H2 NLNZVWQRJHUCOA-UHFFFAOYSA-N
MMV1576786 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCN4CC5(COC5)C4)N32 InChI=1S/C19H19F2N5O3/c20-18(21)29-14-3-1-13(2-4-14)17-24-23-15-7-22-8-16(26(15)17)28-6-5-25-9-19(10-25)11-27-12-19/h1-4,7-8,18H,5-6,9-12H2 CWOUGAWUCYKRFC-UHFFFAOYSA-N
MMV1576787 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4=CC=C(CO)C=C4)N32 InChI=1S/C20H16F2N4O3/c21-20(22)29-16-7-5-15(6-8-16)19-25-24-17-9-23-10-18(26(17)19)28-12-14-3-1-13(11-27)2-4-14/h1-10,20,27H,11-12H2 VIQWBWLDUDXSBJ-UHFFFAOYSA-N
MMV1576788 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4COC4)N32 InChI=1S/C17H16F2N4O3/c18-17(19)26-13-3-1-12(2-4-13)16-22-21-14-7-20-8-15(23(14)16)25-6-5-11-9-24-10-11/h1-4,7-8,11,17H,5-6,9-10H2 VMXSRABLXQMXLK-UHFFFAOYSA-N
MMV1576789 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4(OCCO4)C5=CC(F)=C(F)C=C5)N32 InChI=1S/C22H16F4N4O4/c23-16-6-3-14(9-17(16)24)22(32-7-8-33-22)12-31-19-11-27-10-18-28-29-20(30(18)19)13-1-4-15(5-2-13)34-21(25)26/h1-6,9-11,21H,7-8,12H2 UAZNIGDYRZOARG-UHFFFAOYSA-N
MMV1576790 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC/C4=C/BBBBB[BH]5[BH]([H]5)BB4)N32.[Cs+] InChI=1S/C16H22B9F2N4O2.Cs/c26-16(27)33-12-3-1-10(2-4-12)15-30-29-13-8-28-9-14(31(13)15)32-6-5-11-7-17-19-20-21-23-25-24(34-25)22-18-11;/h1-4,7-9,16-25H,5-6H2;/q;+1/b11-7-; GZUNPULXOLJYSG-AJULUCINSA-N
MMV1576791 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(N(CC)CC)C4=CC(F)=C(F)C=C4)N32 InChI=1S/C24H23F4N5O2/c1-3-32(4-2)20(16-7-10-18(25)19(26)11-16)14-34-22-13-29-12-21-30-31-23(33(21)22)15-5-8-17(9-6-15)35-24(27)28/h5-13,20,24H,3-4,14H2,1-2H3 FFKUJTSUMDVIQH-UHFFFAOYSA-N
MMV1576792 FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(N(CC)C)C4=CC(F)=C(F)C=C4)N32 InChI=1S/C23H21F4N5O2/c1-3-31(2)19(15-6-9-17(24)18(25)10-15)13-33-21-12-28-11-20-29-30-22(32(20)21)14-4-7-16(8-5-14)34-23(26)27/h4-12,19,23H,3,13H2,1-2H3 XPBTWBXREHLVRP-UHFFFAOYSA-N
MMV1576793 FC1=CC(CCOC2=CN=CC3=NN=C(C4=CC=C(C(N)=O)C=C4)N32)=CC=C1F InChI=1S/C20H15F2N5O2/c21-15-6-1-12(9-16(15)22)7-8-29-18-11-24-10-17-25-26-20(27(17)18)14-4-2-13(3-5-14)19(23)28/h1-6,9-11H,7-8H2,(H2,23,28) INLVQLIAJLYDGP-UHFFFAOYSA-N
MMV1576794 FC1=CC(CCOC2=CN=CC3=NN=C(C4=CC(C(N)=O)=CC=C4)N32)=CC=C1F InChI=1S/C20H15F2N5O2/c21-15-5-4-12(8-16(15)22)6-7-29-18-11-24-10-17-25-26-20(27(17)18)14-3-1-2-13(9-14)19(23)28/h1-5,8-11H,6-7H2,(H2,23,28) SUVZMBHYRLCWQO-UHFFFAOYSA-N
MMV1576795 FC1=CC(CCOC2=CN=CC3=NN=C(C4=CC=C(C(N(C)C)=O)C=C4)N32)=CC=C1F InChI=1S/C22H19F2N5O2/c1-28(2)22(30)16-6-4-15(5-7-16)21-27-26-19-12-25-13-20(29(19)21)31-10-9-14-3-8-17(23)18(24)11-14/h3-8,11-13H,9-10H2,1-2H3 VILLYIKHHVUPAT-UHFFFAOYSA-N
MMV1576796 BrC1=NN=C2C=NC=C(OCCC3=CC(F)=C(F)C=C3)N21 InChI=1S/C13H9BrF2N4O/c14-13-19-18-11-6-17-7-12(20(11)13)21-4-3-8-1-2-9(15)10(16)5-8/h1-2,5-7H,3-4H2 MNOZFILPXCZGRJ-UHFFFAOYSA-N
14th August 2017 @ 02:39

A set of 26 Series 4 Triazolopyrazine compounds were sent to have their efficacy evaluated against Plasmodium flaciparum in-vitro at Dundee (GitHub issue #517)

The data has been posted here

Strings:

MMV1557931

IC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC(F)=C(F)C=C4)N32       InChI=1S/C19H13F2IN4O/c20-15-6-1-12(9-16(15)21)7-8-27-18-11-23-10-17-24-25-19(26(17)18)13-2-4-14(22)5-3-13/h1-6,9-11H,7-8H2                                                                       SYOXDOQMLHMQGB-UHFFFAOYSA-N

MMV1557932

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(C4=CC(F)=C(F)C=C4)=O)N32 InChI=1S/C20H12F4N4O3/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/h1-9,20H,10H2                               OPCIMEMUOABUMK-UHFFFAOYSA-N

MMV1557933

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(OC)(OC)C4=CC(F)=C(F)C=C4)N32 InChI=1S/C22H18F4N4O4/c1-31-22(32-2,14-5-8-16(23)17(24)9-14)12-33-19-11-27-10-18-28-29-20(30(18)19)13-3-6-15(7-4-13)34-21(25)26/h3-11,21H,12H2,1-2H3                       HFRRKTROCJVLKP-UHFFFAOYSA-N

MMV1557934

FS(F)(F)(F)(F)C(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC=CC=C4)N32   InChI=1S/C19H15F5N4OS/c20-30(21,22,23,24)16-8-6-15(7-9-16)19-27-26-17-12-25-13-18(28(17)19)29-11-10-14-4-2-1-3-5-14/h1-9,12-13H,10-11H2                             PEMORNCGKKXBCP-UHFFFAOYSA-N

MMV1557935

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4(CC5C6)CC6CC@@HC4)N32   InChI=1S/C24H26F2N4O2/c25-23(26)32-19-3-1-18(2-4-19)22-29-28-20-13-27-14-21(30(20)22)31-6-5-24-10-15-7-16(11-24)9-17(8-15)12-24/h1-4,13-17,23H,5-12H2/t15-,16?,17?,24?BSXLJNOXQMXUOB-CRFYJIHUSA-N

MMV1557936

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OC(C)CC4=CC=CC=C4)N32   InChI=1S/C21H18F2N4O2/c1-14(11-15-5-3-2-4-6-15)28-19-13-24-12-18-25-26-20(27(18)19)16-7-9-17(10-8-16)29-21(22)23/h2-10,12-14,21H,11H2,1H3                                         HJOHTEUEFDSADX-UHFFFAOYSA-N

MMV1557937

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC45CC@@HC[C@@h]6C4)N32   InChI=1S/C23H24F2N4O2/c24-22(25)31-18-3-1-17(2-4-18)21-28-27-19-11-26-12-20(29(19)21)30-13-23-8-14-5-15(9-23)7-16(6-14)10-23/h1-4,11-12,14-16,22H,5-10,13H2/t14-,15+,16-,23?PIOOGPDPQVQAFQ-QUXYOMGYSA-N

MMV1557938

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4C[C@H]5C=C[C@@h]4C5)N32   InChI=1S/C20H18F2N4O2/c21-20(22)28-16-5-3-13(4-6-16)19-25-24-17-9-23-10-18(26(17)19)27-11-15-8-12-1-2-14(15)7-12/h1-6,9-10,12,14-15,20H,7-8,11H2/t12-,14+,15?/m0/s1 OMOCZBKUEFTIAC-DJIKBVBFSA-N

MMV1557939

CC1(C)[C@@h]2C[C@H]1C(CCOC3=CN=CC4=NN=C(C5=CC=C(OC(F)F)C=C5)N43)=CC2 InChI=1S/C23H24F2N4O2/c1-23(2)16-6-3-14(18(23)11-16)9-10-30-20-13-26-12-19-27-28-21(29(19)20)15-4-7-17(8-5-15)31-22(24)25/h3-5,7-8,12-13,16,18,22H,6,9-11H2,1-2H3/t16-,18-/m0/s1                                                                                             PQILDBPUDLGKJU-WMZOPIPTSA-N

MMV1557940

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC(C4=CC=CC=C4)=O)N32 InChI=1S/C20H14F2N4O3/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/h1-11,20H,12H2                                                         MQSMCJANEPVRGE-UHFFFAOYSA-N

MMV1557941

ClC(C=C1)=CC(Cl)=C1C2=NN=C3C=NC=C(OCC45CC@@HC[C@@h]6C4)N32 InChI=1S/C22H22Cl2N4O/c23-16-1-2-17(18(24)6-16)21-27-26-19-10-25-11-20(28(19)21)29-12-22-7-13-3-14(8-22)5-15(4-13)9-22/h1-2,6,10-11,13-15H,3-5,7-9,12H2/t13-,14+,15-,22?XRHQAPBKYTXPOW-HBJUSLLUSA-N

MMV1557942

ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC45CC@@HC[C@@h]6C4)N32 InChI=1S/C22H23ClN4O/c23-18-3-1-17(2-4-18)21-26-25-19-11-24-12-20(27(19)21)28-13-22-8-14-5-15(9-22)7-16(6-14)10-22/h1-4,11-12,14-16H,5-10,13H2/t14-,15+,16-,22?         MFXXXMMQULKXIX-GGTBJBEQSA-N

MMV1557943

CC1(C)[C@@h]2C[C@H]1C(CCOC3=CN=CC4=NN=C(C5=C(Cl)C=C(Cl)C=C5)N43)=CC2 InChI=1S/C22H22Cl2N4O/c1-22(2)14-4-3-13(17(22)9-14)7-8-29-20-12-25-11-19-26-27-21(28(19)20)16-6-5-15(23)10-18(16)24/h3,5-6,10-12,14,17H,4,7-9H2,1-2H3/t14-,17-/m0/s1 OYFPJLPMJIFAIS-YOEHRIQHSA-N

MMV1557944

CC1(C)[C@@h]2C[C@H]1C(CCOC3=CN=CC4=NN=C(C5=CC=C(Cl)C=C5)N43)=CC2 InChI=1S/C22H23ClN4O/c1-22(2)16-6-3-14(18(22)11-16)9-10-28-20-13-24-12-19-25-26-21(27(19)20)15-4-7-17(23)8-5-15/h3-5,7-8,12-13,16,18H,6,9-11H2,1-2H3/t16-,18-/m0/s1 BDWPPKIAXRRNII-WMZOPIPTSA-N

MMV1557945

ClC(C=C1)=CC(Cl)=C1C2=NN=C3C=NC=C(OCC4C[C@H]5C=C[C@@h]4C5)N32 InChI=1S/C19H16Cl2N4O/c20-14-3-4-15(16(21)7-14)19-24-23-17-8-22-9-18(25(17)19)26-10-13-6-11-1-2-12(13)5-11/h1-4,7-9,11-13H,5-6,10H2/t11-,12+,13?/m0/s1                         OLAUIVKJLBCHFE-LAGVYOHYSA-N

MMV1557946

ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCC4C[C@H]5C=C[C@@h]4C5)N32 InChI=1S/C19H17ClN4O/c20-16-5-3-13(4-6-16)19-23-22-17-9-21-10-18(24(17)19)25-11-15-8-12-1-2-14(15)7-12/h1-6,9-10,12,14-15H,7-8,11H2/t12-,14+,15?/m0/s1                       OWTVMOKESSEJOP-DJIKBVBFSA-N

MMV1557948

O=C(NC1=CC=NC=C1)C2=CN=CC3=NN=C(C4=CC=CC=C4)N32               InChI=1S/C17H12N6O/c24-17(20-13-6-8-18-9-7-13)14-10-19-11-15-21-22-16(23(14)15)12-4-2-1-3-5-12/h1-11H,(H,18,20,24)                                                                               JWMBXLLOVDKXRE-UHFFFAOYSA-N

MMV1557947

C12=NN=C(C3=CC=NC=C3)N1C(OCCC4=CC=CC=C4)=CN=C2                   InChI=1S/C18H15N5O/c1-2-4-14(5-3-1)8-11-24-17-13-20-12-16-21-22-18(23(16)17)15-6-9-19-10-7-15/h1-7,9-10,12-13H,8,11H2                                                                           BSTOZULDVQMNLS-UHFFFAOYSA-N

MMV1557950

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OC/C(C4=CC=CC=C4)=N/O)N32 InChI=1S/C20H15F2N5O3/c21-20(22)30-15-8-6-14(7-9-15)19-25-24-17-10-23-11-18(27(17)19)29-12-16(26-28)13-4-2-1-3-5-13/h1-11,20,28H,12H2/b26-16-                                   VJSBQKQNONLQQJ-QQXSKIMKSA-N

MMV1557949

FC(C=C1)=C(F)C=C1CCOC2=CN=CC3=NN=C(C4=CC=CC=C4)N32         InChI=1S/C19H14F2N4O/c20-15-7-6-13(10-16(15)21)8-9-26-18-12-22-11-17-23-24-19(25(17)18)14-4-2-1-3-5-14/h1-7,10-12H,8-9H2                                               RGEIFMMWUNGFHD-UHFFFAOYSA-N

MMV025100

NS(C1=CC(C2=CC3=NC=NC(N)=C3S2)=CC=C1)(=O)=O                     InChI=1S/C12H10N4O2S2/c13-12-11-9(15-6-16-12)5-10(19-11)7-2-1-3-8(4-7)20(14,17)18/h1-6H,(H2,13,15,16)(H2,14,17,18)                                                                               MQMXDJVOZKMSNT-UHFFFAOYSA-N

MMV897709

FC(C=C1)=C(F)C=C1C(OC)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C21H15F2N5O2/c1-29-18(15-6-7-16(22)17(23)8-15)12-30-20-11-25-10-19-26-27-21(28(19)20)14-4-2-13(9-24)3-5-14/h2-8,10-11,18H,12H2,1H3                           PERKBMZWWUEZNJ-UHFFFAOYSA-N

MMV1557952

FC(C=C1)=C(F)C=C1C@@HCOC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C21H15F2N5O2/c1-29-18(15-6-7-16(22)17(23)8-15)12-30-20-11-25-10-19-26-27-21(28(19)20)14-4-2-13(9-24)3-5-14/h2-8,10-11,18H,12H2,1H3/t18-/m0/s1         PERKBMZWWUEZNJ-SFHVURJKSA-N

MMV1557951

FC(C=C1)=C(F)C=C1C@HCOC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C21H15F2N5O2/c1-29-18(15-6-7-16(22)17(23)8-15)12-30-20-11-25-10-19-26-27-21(28(19)20)14-4-2-13(9-24)3-5-14/h2-8,10-11,18H,12H2,1H3/t18-/m1/s1         PERKBMZWWUEZNJ-GOSISDBHSA-N

MMV1557953

FC(C=C1)=C(F)C=C1C(OC)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32 InChI=1S/C21H15F2N5O2/c1-29-18(15-6-7-16(22)17(23)8-15)12-30-20-11-25-10-19-26-27-21(28(19)20)14-4-2-13(9-24)3-5-14/h2-8,10-11,18H,12H2,1H3                           PERKBMZWWUEZNJ-UHFFFAOYSA-N

MMV1557962

C12=NN=C(N3CCCCC3)N1C(OCCC4=CC=CC=C4)=CN=C2                           InChI=1S/C18H21N5O/c1-3-7-15(8-4-1)9-12-24-17-14-19-13-16-20-21-18(23(16)17)22-10-5-2-6-11-22/h1,3-4,7-8,13-14H,2,5-6,9-12H2                                                               QFNWKXKUHMYRFI-UHFFFAOYSA-N

13th February 2017 @ 00:46

Consult was in GHI479. New data received Feb 9th 2017. Raw data attached. Relevant discussion: GHI484. This post authoured by Mat Todd.

New Frontrunner Met/Physchem data

Attached Files
27th January 2017 @ 00:26

A set of 16 Series 4 Triazolopyrazine Frontrunner compounds were sent to have their efficacy re-evaluated against Plasmodium falciparum in-vitro at Dundee.

N.B. Potency values are an average of 2 runs. In one case (MMV672687), the 2 runs gave more-divergent-than-ideal values, however the average is still reported.

Discussion of the Frontrunner compounds and previous in-vitro data can be found here.

The following results were obtained:

Brief comments:

In comparison with the previous Frontrunner data linked above, all but one of the new potency values were slightly higher than before, but all values still indicate the active compounds were active etc.

MMV672687 had better activity than before even considering the N.B. above.

Strings:

MMV663915 OSM-S-293

ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC=CC=C4)N32             InChI=1S/C19H15ClN4O/c20-16-8-6-15(7-9-16)19-23-22-17-12-21-13-18(24(17)19)25-11-10-14-4-2-1-3-5-14/h1-9,12-13H,10-11H2

MMV670936 OSM-S-366

FC1=C(F)C=CC(CCOC2=CN=CC3=NN=C(C4=CN=C(C(F)(F)F)C=C4)N32)=C1 InChI=1S/C19H12F5N5O/c20-13-3-1-11(7-14(13)21)5-6-30-17-10-25-9-16-27-28-18(29(16)17)12-2-4-15(26-8-12)19(22,23)24/h1-4,7-10H,5-6H2

MMV639565 OSM-S-272

ClC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC(F)=C(F)C=C4)N32 InChI=1S/C19H13ClF2N4O/c20-14-4-2-13(3-5-14)19-25-24-17-10-23-11-18(26(17)19)27-8-7-12-1-6-15(21)16(22)9-12/h1-6,9-11H,7-8H2

MMV897709 OSM-S-218

FC1=C(F)C=CC(C(OC)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32)=C1 InChI=1S/C21H15F2N5O2/c1-29-18(15-6-7-16(22)17(23)8-15)12-30-20-11-25-10-19-26-27-21(28(19)20)14-4-2-13(9-24)3-5-14/h2-8,10-11,18H,12H2,1H3

MMV688895 OSM-S-278

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

MMV672687 OSM-S-390

OC(C1=CC(F)=C(F)C=C1)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 

MMV688896 OSM-S-279

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

MMV693155 OSM-S-353

OCC(C1=CC=CC=C1)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C21H18F2N4O3/c22-21(23)30-17-8-6-15(7-9-17)20-26-25-18-10-24-11-19(27(18)20)29-13-16(12-28)14-4-2-1-3-5-14/h1-11,16,21,28H,12-13H2

MMV897763 OSM-S-389

FC1=C(F)C=CC(C(N(C)C)COC2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32)=C1 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 

MMV669000 OSM-S-177

O=C(N1CC(C=CC=C2)=C2C1)C3=CN=CC4=NN=C(C5=CC=C(OC(F)F)C=C5)N43 InChI=1S/C21H15F2N5O2/c22-21(23)30-16-7-5-13(6-8-16)19-26-25-18-10-24-9-17(28(18)19)20(29)27-11-14-3-1-2-4-15(14)12-27/h1-10,21H,11-12H2 

MMV670246 OSM-S-367

O=C(NC1=CC=C(Cl)C=C1)C2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C19H12ClF2N5O2/c20-12-3-5-13(6-4-12)24-18(28)15-9-23-10-16-25-26-17(27(15)16)11-1-7-14(8-2-11)29-19(21)22/h1-10,19H,(H,24,28)

MMV670767 OSM-S-379

O=C(NC1=CC=C(F)C(Cl)=C1)C2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C19H11ClF3N5O2/c20-13-7-11(3-6-14(13)21)25-18(29)15-8-24-9-16-26-27-17(28(15)16)10-1-4-12(5-2-10)30-19(22)23/h1-9,19H,(H,25,29)

MMV670944 OSM-S-175

O=C(NC1=CC=NC(C(F)(F)F)=C1)C2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 InChI=1S/C19H11F5N6O2/c20-18(21)32-12-3-1-10(2-4-12)16-29-28-15-9-25-8-13(30(15)16)17(31)27-11-5-6-26-14(7-11)19(22,23)24/h1-9,18H,(H,26,27,31)

MMV675718 OSM-S-201

O=C(NC1=CC=CC(Cl)=C1C)C2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 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)

MMV675946 OSM-S-946

O=C(NC1=CC=CC(Cl)=C1F)C2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 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)

MMV675947 OSM-S-254

O=C(NC1=C(C)C=CC(Cl)=C1)C2=CN=CC3=NN=C(C4=CC=C(OC(F)F)C=C4)N32 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)

Attached Files
26th January 2017 @ 22:51

A new set of 20 Series 4 Triazolopyrazine compounds were sent to have their efficacy evaluated against Plasmodium falciparum in-vitro at Dundee.

N.B. Potency values are an average of 2 runs. In certain cases (MMV897697, MMV897698, MMV897699, MMV897700, MMV897708, MMV897714), the 2 runs gave more-divergent-than-ideal values, however the averages are still reported.

The following results were obtained:

Brief comments:

Thioether, sulfoxide and sulfone were inactive again. The comparative ether compounds showed good to moderate activity.

Left hand cubane bioisosteres showed good to moderate activty. Right hand isosteres were inactive.

All ether-triazole linked compounds were inactive.

Both 3- and 4-OMe compounds were active

MMV897708 showed slightly reduced activity to the OCHF2 analogue (MMV672687). MMV897707 was inactive compared with the active OCHF2 analogue (MMV897763).

Compounds with a methylated benzylic position showed moderate activity.

MMV897706 and MMV897705 were inactive.

Strings:

MMV693164 OSM-S-363

FC(F)OC1=CC=C(C2=NN=C3C=NC=C(N32)SCCC4=CC=CC=C4)C=C1       InChI=1S/C20H16F2N4OS/c21-20(22)27-16-8-6-15(7-9-16)19-25-24-17-12-23-13-18(26(17)19)28-11-10-14-4-2-1-3-5-14/h1-9,12-13,20H,10-11H2

MMV693167 OSM-S-364

O=S(CCC1=CC=CC=C1)C(N23)=CN=CC2=NN=C3C4=CC=C(OC(F)F)C=C4 InChI=1S/C20H16F2N4O2S/c21-20(22)28-16-8-6-15(7-9-16)19-25-24-17-12-23-13-18(26(17)19)29(27)11-10-14-4-2-1-3-5-14/h1-9,12-13,20H,10-11H2

MMV693166 OSM-S-365

FC(F)OC1=CC=C(C2=NN=C3C=NC=C(N32)S(CCC4=CC=CC=C4)(=O)=O)C=C1 InChI=1S/C20H16F2N4O3S/c21-20(22)29-16-8-6-15(7-9-16)19-25-24-17-12-23-13-18(26(17)19)30(27,28)11-10-14-4-2-1-3-5-14/h1-9,12-13,20H,10-11H2

MMV897697 OSM-S-368

FC(F)OC1=CC=C(C2=NN=C3C=NC=C(N32)OCC4=CC=CC=C4)C=C1     InChI=1S/C19H14F2N4O2/c20-19(21)27-15-8-6-14(7-9-15)18-24-23-16-10-22-11-17(25(16)18)26-12-13-4-2-1-3-5-13/h1-11,19H,12H2

MMV897698 OSM-S-369

FC(F)OC1=CC=C(C2=NN=C3C=NC=C(N32)OCCC4=CC=CC=C4)C=C1   InChI=1S/C20H16F2N4O2/c21-20(22)28-16-8-6-15(7-9-16)19-25-24-17-12-23-13-18(26(17)19)27-11-10-14-4-2-1-3-5-14/h1-9,12-13,20H,10-11H2

MMV897699 OSM-S-370

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCCC45C6C7C4C8C7C6C58)N32 InChI=1S/C23H20F2N4O2/c24-22(25)31-11-4-2-10(3-5-11)21-28-27-12-8-26-9-13(29(12)21)30-7-1-6-23-18-15-14-16(18)20(23)17(14)19(15)23/h2-5,8-9,14-20,22H,1,6-7H2

MMV897700 OSM-S-371

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC45C6C7C4C8C7C6C58)N32 InChI=1S/C22H18F2N4O2/c23-21(24)30-10-3-1-9(2-4-10)20-27-26-11-7-25-8-12(28(11)20)29-6-5-22-17-14-13-15(17)19(22)16(13)18(14)22/h1-4,7-8,13-19,21H,5-6H2

MMV897704 OSM-S-375

FC(C=C1)=C(F)C=C1CCOC2=CN=CC3=NN=C(C45C6C7C4C8C7(I)C6C58)N32 InChI=1S/C21H15F2IN4O/c22-9-2-1-8(5-10(9)23)3-4-29-12-7-25-6-11-26-27-19(28(11)12)20-13-16-14(20)18-15(20)17(13)21(16,18)24/h1-2,5-7,13-18H,3-4H2

MMV897710 OSM-S-382

IC12C3C4C5(C3C1C5C24)C6=NN=C7C=NC=C(C(NC8=CC(C(F)(F)F)=NC=C8)=O)N76 InChI=1S/C20H12F3IN6O/c21-20(22,23)8-3-6(1-2-26-8)27-16(31)7-4-25-5-9-28-29-17(30(7)9)18-10-13-11(18)15-12(18)14(10)19(13,15)24/h1-5,10-15H,(H,26,27,31)

MMV897701 OSM-S-372

FC(F)OC1=CC=C(C2=NN=C3C=NC=C(N32)OCC4=CN(CC5=CC=CC=C5)N=N4)C=C1 InChI=1S/C22H17F2N7O2/c23-22(24)33-18-8-6-16(7-9-18)21-28-27-19-10-25-11-20(31(19)21)32-14-17-13-30(29-26-17)12-15-4-2-1-3-5-15/h1-11,13,22H,12,14H2

MMV897702 OSM-S-373

FC(F)OC1=CC=C(C2=NN=C3C=NC=C(N32)OCC4=CN(C5=CC=CC=C5)N=N4)C=C1 InChI=1S/C21H15F2N7O2/c22-21(23)32-17-8-6-14(7-9-17)20-27-26-18-10-24-11-19(30(18)20)31-13-15-12-29(28-25-15)16-4-2-1-3-5-16/h1-12,21H,13H2

MMV897703 OSM-S-374

ClC1=CN=CC(N2N=NC(COC(N34)=CN=CC3=NN=C4C5=CC=C(C=C5)OC(F)F)=C2)=N1 InChI=1S/C19H12ClF2N9O2/c20-14-5-23-6-15(25-14)30-9-12(26-29-30)10-32-17-8-24-7-16-27-28-18(31(16)17)11-1-3-13(4-2-11)33-19(21)22/h1-9,19H,10H2

MMV897711 OSM-S-383

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC(OC)=CC=C4)N32 InChI=1S/C21H18F2N4O3/c1-28-17-4-2-3-14(11-17)9-10-29-19-13-24-12-18-25-26-20(27(18)19)15-5-7-16(8-6-15)30-21(22)23/h2-8,11-13,21H,9-10H2,1H3

MMV897712 OSM-S-384

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OCCC4=CC=C(OC)C=C4)N32 InChI=1S/C21H18F2N4O3/c1-28-16-6-2-14(3-7-16)10-11-29-19-13-24-12-18-25-26-20(27(18)19)15-4-8-17(9-5-15)30-21(22)23/h2-9,12-13,21H,10-11H2,1H3

MMV897708 OSM-S-376

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

MMV897707 OSM-S-378

FC1=C(F)C=CC(C(N(C)C)COC2=CN=CC3=NN=C(C4=CC=C(C#N)C=C4)N32)=C1 InChI=1S/C22H18F2N6O/c1-29(2)19(16-7-8-17(23)18(24)9-16)13-31-21-12-26-11-20-27-28-22(30(20)21)15-5-3-14(10-25)4-6-15/h3-9,11-12,19H,13H2,1-2H3

MMV897713 OSM-S-385

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OC(C)C4=CC=C(F)C(F)=C4)N32 InChI=1S/C20H14F4N4O2/c1-11(13-4-7-15(21)16(22)8-13)29-18-10-25-9-17-26-27-19(28(17)18)12-2-5-14(6-3-12)30-20(23)24/h2-11,20H,1H3

MMV897714 OSM-S-386

FC(F)OC(C=C1)=CC=C1C2=NN=C3C=NC=C(OC(C)C4=CC=C(C#N)C=C4)N32 InChI=1S/C21H15F2N5O2/c1-13(15-4-2-14(10-24)3-5-15)29-19-12-25-11-18-26-27-20(28(18)19)16-6-8-17(9-7-16)30-21(22)23/h2-9,11-13,21H,1H3

MMV897706 OSM-S-387

FC(C=C1)=C(F)C=C1CCOC2=CN=CC3=NN=C([H])N32                           InChI=1S/C13H10F2N4O/c14-10-2-1-9(5-11(10)15)3-4-20-13-7-16-6-12-18-17-8-19(12)13/h1-2,5-8H,3-4H2

MMV897705 OSM-S-388

OC1=CN=CC2=NN=C(N3CCCCC3)N21                                                     InChI=1S/C10H13N5O/c16-9-7-11-6-8-12-13-10(15(8)9)14-4-2-1-3-5-14/h6-7,16H,1-5H2

Attached Files