DK3137455T3 - Triaminopyrimidine compounds for the prevention or treatment of malaria - Google Patents

Info

Publication number

DK3137455T3

DK3137455T3 DK15713170.7T DK15713170T DK3137455T3 DK 3137455 T3 DK3137455 T3 DK 3137455T3 DK 15713170 T DK15713170 T DK 15713170T DK 3137455 T3 DK3137455 T3 DK 3137455T3

Authority

DK

Denmark

Prior art keywords

methyl

cyclopropyl

diamine

fluoro

pyridyl

Prior art date

2014-04-28

Links

• Espacenet
• Global Dossier
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• 201000004792 malaria Diseases 0.000 title claims description 30
• 238000011282 treatment Methods 0.000 title claims description 27
• 230000002265 prevention Effects 0.000 title claims description 4
• CSNFMBGHUOSBFU-UHFFFAOYSA-N pyrimidine-2,4,5-triamine Chemical class NC1=NC=C(N)C(N)=N1 CSNFMBGHUOSBFU-UHFFFAOYSA-N 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 137
• 150000003839 salts Chemical class 0.000 claims description 56
• -1 4-cyclopropyl-5-fluoro-6-methyl-2-pyridyl Chemical group 0.000 claims description 49
• 239000000203 mixture Substances 0.000 claims description 41
• 239000008194 pharmaceutical composition Substances 0.000 claims description 28
• 125000000217 alkyl group Chemical group 0.000 claims description 27
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 241000224016 Plasmodium Species 0.000 claims description 16
• 229910052739 hydrogen Inorganic materials 0.000 claims description 16
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
• 238000004519 manufacturing process Methods 0.000 claims description 12
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
• 239000002207 metabolite Substances 0.000 claims description 11
• 239000003430 antimalarial agent Substances 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 10
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 10
• OVCDSSHSILBFBN-UHFFFAOYSA-N Amodiaquine Chemical compound C1=C(O)C(CN(CC)CC)=CC(NC=2C3=CC=C(Cl)C=C3N=CC=2)=C1 OVCDSSHSILBFBN-UHFFFAOYSA-N 0.000 claims description 8
• 229960001444 amodiaquine Drugs 0.000 claims description 8
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 239000012453 solvate Substances 0.000 claims description 7
• FOHHNHSLJDZUGQ-VWLOTQADSA-N Halofantrine Chemical compound FC(F)(F)C1=CC=C2C([C@@H](O)CCN(CCCC)CCCC)=CC3=C(Cl)C=C(Cl)C=C3C2=C1 FOHHNHSLJDZUGQ-VWLOTQADSA-N 0.000 claims description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 6
• 208000030852 Parasitic disease Diseases 0.000 claims description 6
• 229960003242 halofantrine Drugs 0.000 claims description 6
• XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 0.000 claims description 5
• 229930101531 artemisinin Natural products 0.000 claims description 5
• 239000000460 chlorine Substances 0.000 claims description 5
• 229910052801 chlorine Inorganic materials 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 150000004677 hydrates Chemical class 0.000 claims description 5
• 229960001962 mefloquine Drugs 0.000 claims description 5
• YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical compound NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 claims description 5
• SARMGXPVOFNNNG-UHFFFAOYSA-N 1-[amino-(4-chloroanilino)methylidene]-2-propan-2-ylguanidine;hydron;chloride Chemical compound Cl.CC(C)N=C(N)N=C(N)NC1=CC=C(Cl)C=C1 SARMGXPVOFNNNG-UHFFFAOYSA-N 0.000 claims description 4
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 4
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 4
• 229960003722 doxycycline Drugs 0.000 claims description 4
• XQTWDDCIUJNLTR-CVHRZJFOSA-N doxycycline monohydrate Chemical compound O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H](N(C)C)[C@@H]1[C@H]2O XQTWDDCIUJNLTR-CVHRZJFOSA-N 0.000 claims description 4
• 229910052731 fluorine Inorganic materials 0.000 claims description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
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• 238000005576 amination reaction Methods 0.000 claims description 3
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• BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical class C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 claims description 3
• 239000011737 fluorine Substances 0.000 claims description 3
• 229910052736 halogen Inorganic materials 0.000 claims description 3
• 150000002367 halogens Chemical class 0.000 claims description 3
• 229910052763 palladium Inorganic materials 0.000 claims description 3
• DLYPREQTTOHKSM-UHFFFAOYSA-N 7-chloro-n-[[2-[(dimethylamino)methyl]cyclopenta-1,4-dien-1-yl]methyl]quinolin-4-amine;cyclopenta-1,3-diene;iron(2+) Chemical compound [Fe+2].C1C=CC=[C-]1.C1=[C-]CC(CN(C)C)=C1CNC1=CC=NC2=CC(Cl)=CC=C12 DLYPREQTTOHKSM-UHFFFAOYSA-N 0.000 claims description 2
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• PRIKOVXXBHBBFQ-UHFFFAOYSA-N C1(CC1)C1=CC(=NC(=C1F)C)NC1=NC=C(C(=N1)NC1=NN(N=C1)C)N1CC(N(CC1)C)C Chemical compound C1(CC1)C1=CC(=NC(=C1F)C)NC1=NC=C(C(=N1)NC1=NN(N=C1)C)N1CC(N(CC1)C)C PRIKOVXXBHBBFQ-UHFFFAOYSA-N 0.000 claims description 2
• 235000001258 Cinchona calisaya Nutrition 0.000 claims description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
• 229960000981 artemether Drugs 0.000 claims description 2
• 229960002521 artenimol Drugs 0.000 claims description 2
• BJDCWCLMFKKGEE-ISOSDAIHSA-N artenimol Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-ISOSDAIHSA-N 0.000 claims description 2
• 229960003159 atovaquone Drugs 0.000 claims description 2
• KUCQYCKVKVOKAY-CTYIDZIISA-N atovaquone Chemical compound C1([C@H]2CC[C@@H](CC2)C2=C(C(C3=CC=CC=C3C2=O)=O)O)=CC=C(Cl)C=C1 KUCQYCKVKVOKAY-CTYIDZIISA-N 0.000 claims description 2
• 229930016266 dihydroartemisinin Natural products 0.000 claims description 2
• SXYIRMFQILZOAM-HVNFFKDJSA-N dihydroartemisinin methyl ether Chemical compound C1C[C@H]2[C@H](C)CC[C@H]3[C@@H](C)[C@@H](OC)O[C@H]4[C@]32OO[C@@]1(C)O4 SXYIRMFQILZOAM-HVNFFKDJSA-N 0.000 claims description 2
• 229950010451 ferroquine Drugs 0.000 claims description 2
• 229960000901 mepacrine Drugs 0.000 claims description 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
• 229960005179 primaquine Drugs 0.000 claims description 2
• INDBQLZJXZLFIT-UHFFFAOYSA-N primaquine Chemical compound N1=CC=CC2=CC(OC)=CC(NC(C)CCCN)=C21 INDBQLZJXZLFIT-UHFFFAOYSA-N 0.000 claims description 2
• 229960005385 proguanil Drugs 0.000 claims description 2
• 229960001870 proguanil hydrochloride Drugs 0.000 claims description 2
• GPKJTRJOBQGKQK-UHFFFAOYSA-N quinacrine Chemical compound C1=C(OC)C=C2C(NC(C)CCCN(CC)CC)=C(C=CC(Cl)=C3)C3=NC2=C1 GPKJTRJOBQGKQK-UHFFFAOYSA-N 0.000 claims description 2
• 229960000948 quinine Drugs 0.000 claims description 2
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• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
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