Biological Evaluation of Compounds

 

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