EA032314B1 - Трициклические гетероциклические соединения, применимые в качестве ингибиторов tnf - Google Patents

Info

Publication number

EA032314B1

EA032314B1 EA201792025A EA201792025A EA032314B1 EA 032314 B1 EA032314 B1 EA 032314B1 EA 201792025 A EA201792025 A EA 201792025A EA 201792025 A EA201792025 A EA 201792025A EA 032314 B1 EA032314 B1 EA 032314B1

Authority

EA

Eurasian Patent Office

Prior art keywords

phenyl

imidazo

pyridazin

difluoromethoxy

tetrahydropyrido

Prior art date

2015-03-18

Links

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• 239000003112 inhibitor Substances 0.000 title description 4
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• -1 methoxyphenyl Chemical group 0.000 claims description 228
• JPMJNVODBLZHLR-UHFFFAOYSA-N 5h-imidazo[1,2-b]pyridazin-6-one Chemical compound N1C(=O)C=CC2=NC=CN21 JPMJNVODBLZHLR-UHFFFAOYSA-N 0.000 claims description 62
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• VTVRXITWWZGKHV-UHFFFAOYSA-N imidazo[1,2-b]pyridazine Chemical compound N1=CC=CC2=NC=CN21 VTVRXITWWZGKHV-UHFFFAOYSA-N 0.000 claims description 23
• 125000001424 substituent group Chemical group 0.000 claims description 19
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 18
• 125000004526 pyridazin-2-yl group Chemical group N1N(C=CC=C1)* 0.000 claims description 17
• 201000010099 disease Diseases 0.000 claims description 15
• 125000004076 pyridyl group Chemical group 0.000 claims description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
• 125000002757 morpholinyl group Chemical group 0.000 claims description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
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• 239000003937 drug carrier Substances 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 7
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
• VERTYDKHQFEQMO-UHFFFAOYSA-N 12-[4-(2-hydroxypropan-2-yl)phenyl]-3-[2-(trifluoromethoxy)phenyl]-1,4,8,13-tetrazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-6-ol Chemical compound OC(C)(C)C1=CC=C(C=C1)C=1C=CC=2N(N=1)C1=C(N=2)C(CNC1C1=C(C=CC=C1)OC(F)(F)F)O VERTYDKHQFEQMO-UHFFFAOYSA-N 0.000 claims description 5
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• ZDJURXUJJAGERM-UHFFFAOYSA-N 2-[5-[3-[2-(difluoromethoxy)phenyl]-4-oxa-1,8,13-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)C1OCCC=2N=C3N(N=C(C=C3)C=3C=NC(=NC=3)C(C)(C)O)C=21)F ZDJURXUJJAGERM-UHFFFAOYSA-N 0.000 claims description 4
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• JNWGENHPTXAVTH-UHFFFAOYSA-N 1,4,8,13-tetrazatricyclo[7.4.0.02,7]trideca-2,4,6,8-tetraen-6-ol Chemical compound N1N2C(CCC1)=NC1=C2C=NC=C1O JNWGENHPTXAVTH-UHFFFAOYSA-N 0.000 claims 2
• HLSNOMZQZYVRSL-UHFFFAOYSA-N 2-[4-[3-[2-(difluoromethoxy)phenyl]-4-oxa-1,8,13-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]phenyl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)C1OCCC=2N=C3N(N=C(C=C3)C3=CC=C(C=C3)C(C)(C)O)C=21)F HLSNOMZQZYVRSL-UHFFFAOYSA-N 0.000 claims 2
• YGHANWAHRPLDGU-UHFFFAOYSA-N 3-[2-(difluoromethoxy)phenyl]-12-[2-(2-hydroxypropan-2-yl)pyrimidin-5-yl]-1,4,8,13-tetrazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-6-ol Chemical compound FC(OC1=C(C=CC=C1)C1NCC(C=2N=C3N(N=C(C=C3)C=3C=NC(=NC=3)C(C)(C)O)C=21)O)F YGHANWAHRPLDGU-UHFFFAOYSA-N 0.000 claims 2
• PQXVMEVPQIXYQE-UHFFFAOYSA-N 3-methoxyazetidine-1-carbaldehyde Chemical compound COC1CN(C=O)C1 PQXVMEVPQIXYQE-UHFFFAOYSA-N 0.000 claims 2
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• 208000020408 systemic-onset juvenile idiopathic arthritis Diseases 0.000 claims 1
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• 230000014759 maintenance of location Effects 0.000 description 52
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