HUE034721T2 - Szubsztituált 2-alkil-1-oxo-N-fenil-3-heteroaril-1,2,3,4-tetrahidroizokinolin-4-karboxamidok maláriaellenes terápiákhoz - Google Patents

Info

Publication number

HUE034721T2

HUE034721T2 HUE12772470A HUE12772470A HUE034721T2 HU E034721 T2 HUE034721 T2 HU E034721T2 HU E12772470 A HUE12772470 A HU E12772470A HU E12772470 A HUE12772470 A HU E12772470A HU E034721 T2 HUE034721 T2 HU E034721T2

Authority

HU

Hungary

Prior art keywords

oxo

carboxamide

pyrazol

fluoro

methyl

Prior art date

2011-08-25

Links

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• 239000003430 antimalarial agent Substances 0.000 title claims description 12
• 230000000078 anti-malarial effect Effects 0.000 title description 20
• 238000002560 therapeutic procedure Methods 0.000 title description 5
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• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 130
• 150000001875 compounds Chemical class 0.000 claims description 120
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 98
• 229910052739 hydrogen Inorganic materials 0.000 claims description 76
• 238000000034 method Methods 0.000 claims description 53
• 239000001257 hydrogen Substances 0.000 claims description 51
• 125000000217 alkyl group Chemical group 0.000 claims description 43
• 125000001153 fluoro group Chemical group F* 0.000 claims description 43
• 239000000203 mixture Substances 0.000 claims description 37
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• 201000004792 malaria Diseases 0.000 claims description 33
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 33
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• KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims description 26
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 24
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• 125000001072 heteroaryl group Chemical group 0.000 claims description 21
• 229910052757 nitrogen Inorganic materials 0.000 claims description 21
• 229910052717 sulfur Inorganic materials 0.000 claims description 20
• 239000011593 sulfur Substances 0.000 claims description 20
• WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 claims description 19
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
• 125000001424 substituent group Chemical group 0.000 claims description 19
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• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 16
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• 238000002360 preparation method Methods 0.000 claims description 14
• 150000003839 salts Chemical class 0.000 claims description 14
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• 239000002253 acid Substances 0.000 claims description 13
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 12
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• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 12
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• BXDZOYLPNAIDOC-UHFFFAOYSA-N N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide Chemical compound CC(C)(C)c1cnc(CSc2cnc(NC(=O)C3CCN(CC(=O)NCCOCCOCCOCCNc4cccc5C(=O)N(C6CCC(=O)NC6=O)C(=O)c45)CC3)s2)o1 BXDZOYLPNAIDOC-UHFFFAOYSA-N 0.000 claims description 11
• 125000001246 bromo group Chemical group Br* 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
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• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
• 229910052740 iodine Inorganic materials 0.000 claims description 8
• 229960001962 mefloquine Drugs 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
• 229960001870 proguanil hydrochloride Drugs 0.000 claims description 8
• OIZSVTOIBNSVOS-UHFFFAOYSA-N 2-(1,1-difluoroethyl)-5-methyl-n-[4-(pentafluoro-$l^{6}-sulfanyl)phenyl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine Chemical compound N12N=C(C(C)(F)F)N=C2N=C(C)C=C1NC1=CC=C(S(F)(F)(F)(F)F)C=C1 OIZSVTOIBNSVOS-UHFFFAOYSA-N 0.000 claims description 7
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
• 229910052794 bromium Inorganic materials 0.000 claims description 7
• 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 7
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
• CKLPLPZSUQEDRT-WPCRTTGESA-N nitd609 Chemical compound O=C1NC2=CC=C(Cl)C=C2[C@@]11C(NC=2C3=CC(F)=C(Cl)C=2)=C3C[C@H](C)N1 CKLPLPZSUQEDRT-WPCRTTGESA-N 0.000 claims description 7
• XLCNVWUKICLURR-UHFFFAOYSA-N oz439 Chemical compound C=1C=C(C2CCC3(CC2)OC2(OO3)C3CC4CC(C3)CC2C4)C=CC=1OCCN1CCOCC1 XLCNVWUKICLURR-UHFFFAOYSA-N 0.000 claims description 7
• 239000012453 solvate Substances 0.000 claims description 7
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
• 235000001258 Cinchona calisaya Nutrition 0.000 claims description 6
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 6
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