EA025863B1 - Карбазолкарбоксамидные соединения - Google Patents

Info

Publication number

EA025863B1

EA025863B1 EA201690012A EA201690012A EA025863B1 EA 025863 B1 EA025863 B1 EA 025863B1 EA 201690012 A EA201690012 A EA 201690012A EA 201690012 A EA201690012 A EA 201690012A EA 025863 B1 EA025863 B1 EA 025863B1

Authority

EA

Eurasian Patent Office

Prior art keywords

carbazole

carboxamide

methylphenyl

mixture

dioxo

Prior art date

2013-06-25

Links

• Espacenet
• Global Dossier
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• GFHHIWFKWFBNRU-UHFFFAOYSA-N 9h-carbazole-1-carboxamide Chemical class C12=CC=CC=C2NC2=C1C=CC=C2C(=O)N GFHHIWFKWFBNRU-UHFFFAOYSA-N 0.000 title claims description 23
• 150000001875 compounds Chemical class 0.000 claims abstract description 320
• 150000003839 salts Chemical class 0.000 claims abstract description 83
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 29
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 18
• -1 3- (8-fluoro-2,4-dioxo-1,2-dihydroquinazolin-3 (4H) -yl) -2-methylphenyl Chemical group 0.000 claims description 175
• 238000011282 treatment Methods 0.000 claims description 30
• 239000003814 drug Substances 0.000 claims description 25
• 229910052739 hydrogen Inorganic materials 0.000 claims description 20
• 238000004519 manufacturing process Methods 0.000 claims description 16
• 229910052698 phosphorus Inorganic materials 0.000 claims description 15
• 239000003937 drug carrier Substances 0.000 claims description 14
• VIRRHNLXPOCKII-UHFFFAOYSA-N 4-[3-(5-fluoro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(methoxymethyl)-9h-carbazole-1-carboxamide Chemical compound O=C1C=C2C(F)=CC=CN2C(=O)N1C1=C(C)C(C=2C=CC(=C3NC=4C(C=23)=CC=C(C=4)COC)C(N)=O)=CC=C1 VIRRHNLXPOCKII-UHFFFAOYSA-N 0.000 claims description 11
• HPPFVYVYCRLUIG-UHFFFAOYSA-N 7-(2-hydroxypropan-2-yl)-4-[3-(6-methoxy-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(=O)C=C3N(C2=O)C=CC(=C3)OC)=CC=C1 HPPFVYVYCRLUIG-UHFFFAOYSA-N 0.000 claims description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
• BPINSDADQGFXNS-UHFFFAOYSA-N 4-[2-chloro-3-(1-methyl-2,4-dioxoquinazolin-3-yl)phenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(Cl)C(N2C(=O)C3=CC=CC=C3N(C2=O)C)=CC=C1 BPINSDADQGFXNS-UHFFFAOYSA-N 0.000 claims description 7
• KXUXXPNDCAWJHM-UHFFFAOYSA-N 4-[2-chloro-3-(8-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)phenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(Cl)C(N2C(=O)C3=CC=CC(F)=C3N(C2=O)C)=CC=C1 KXUXXPNDCAWJHM-UHFFFAOYSA-N 0.000 claims description 7
• RNLHORWOBQSYJE-UHFFFAOYSA-N 4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(methoxymethyl)-9h-carbazole-1-carboxamide Chemical compound O=C1C=C2C(Cl)=CC=CN2C(=O)N1C1=C(C)C(C=2C=CC(=C3NC=4C(C=23)=CC=C(C=4)COC)C(N)=O)=CC=C1 RNLHORWOBQSYJE-UHFFFAOYSA-N 0.000 claims description 7
• KQUDGOWUGZTCKG-UHFFFAOYSA-N 4-[3-(6-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(C3=CC(F)=CC=C3N(C)C2=O)=O)=CC=C1 KQUDGOWUGZTCKG-UHFFFAOYSA-N 0.000 claims description 7
• YSLQGJFYBNLPDI-UHFFFAOYSA-N 7-(2-hydroxypropan-2-yl)-4-[3-(5-methoxy-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(=O)C=C3N(C2=O)C=CC=C3OC)=CC=C1 YSLQGJFYBNLPDI-UHFFFAOYSA-N 0.000 claims description 7
• 238000002560 therapeutic procedure Methods 0.000 claims description 7
• FFVSEFDDGUYDFO-UHFFFAOYSA-N 4-[3-(5,7-dioxo-[1,3]thiazolo[3,2-c]pyrimidin-6-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(N3C=CSC3=CC2=O)=O)=CC=C1 FFVSEFDDGUYDFO-UHFFFAOYSA-N 0.000 claims description 6
• XAJGLHVYSGTVTF-UHFFFAOYSA-N 4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2,2-dimethylpropanoylamino)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(NC(=O)C(C)(C)C)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(N3C=CC=C(Cl)C3=CC2=O)=O)=CC=C1 XAJGLHVYSGTVTF-UHFFFAOYSA-N 0.000 claims description 6
• OPCHAIUSSHIEQR-UHFFFAOYSA-N 4-[3-[3-(4-fluorophenyl)-2,6-dioxopyrimidin-1-yl]-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound CC1=C(C=2C=3C4=CC=C(C=C4NC=3C(C(N)=O)=CC=2)C(C)(C)O)C=CC=C1N(C1=O)C(=O)C=CN1C1=CC=C(F)C=C1 OPCHAIUSSHIEQR-UHFFFAOYSA-N 0.000 claims description 6
• HMFXPCSTCHRNIX-UHFFFAOYSA-N 7-(2-hydroxypropan-2-yl)-4-[3-(7-methoxy-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(=O)C=C3C=CC(=CN3C2=O)OC)=CC=C1 HMFXPCSTCHRNIX-UHFFFAOYSA-N 0.000 claims description 6
• BEVUBRZINAWGDH-UHFFFAOYSA-N 4-[3-(8-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-5-methyl-9h-carbazole-1-carboxamide Chemical compound O=C1N(C)C2=C(F)C=CC=C2C(=O)N1C1=C(C)C(C=2C=CC(=C3NC=4C=C(C=C(C=4C3=2)C)C(C)(C)O)C(N)=O)=CC=C1 BEVUBRZINAWGDH-UHFFFAOYSA-N 0.000 claims description 5
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
• RAGWYGVSFHQCQZ-UHFFFAOYSA-N 7-(2-hydroxypropan-2-yl)-4-[3-(8-methoxy-1-methyl-2,4-dioxoquinazolin-3-yl)-2-methylphenyl]-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(=O)N(C)C3=C(C2=O)C=CC=C3OC)=CC=C1 RAGWYGVSFHQCQZ-UHFFFAOYSA-N 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 3
• 208000037976 chronic inflammation Diseases 0.000 claims 2
• 208000037893 chronic inflammatory disorder Diseases 0.000 claims 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 90
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 49
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• 108010029445 Agammaglobulinaemia Tyrosine Kinase Proteins 0.000 abstract description 2
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• 238000001819 mass spectrum Methods 0.000 description 91
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