CA2980161A1 - Heterocyclic compounds useful as inhibitors of tnf - Google Patents
Heterocyclic compounds useful as inhibitors of tnf Download PDFInfo
- Publication number
- CA2980161A1 CA2980161A1 CA2980161A CA2980161A CA2980161A1 CA 2980161 A1 CA2980161 A1 CA 2980161A1 CA 2980161 A CA2980161 A CA 2980161A CA 2980161 A CA2980161 A CA 2980161A CA 2980161 A1 CA2980161 A1 CA 2980161A1
- Authority
- CA
- Canada
- Prior art keywords
- zero
- substituted
- tetrahydroimidazo
- alkyl
- aryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 150000002391 heterocyclic compounds Chemical class 0.000 title description 6
- 239000003112 inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 288
- 150000003839 salts Chemical class 0.000 claims abstract description 73
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 17
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 14
- 125000003118 aryl group Chemical group 0.000 claims description 76
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 72
- -1 -OH Chemical group 0.000 claims description 53
- 125000000623 heterocyclic group Chemical group 0.000 claims description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 42
- 125000002950 monocyclic group Chemical group 0.000 claims description 34
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 27
- 229910052731 fluorine Inorganic materials 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 24
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 20
- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 12
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- 201000005569 Gout Diseases 0.000 claims description 4
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 4
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 4
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 208000023328 Basedow disease Diseases 0.000 claims description 3
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 206010016207 Familial Mediterranean fever Diseases 0.000 claims description 3
- 208000015023 Graves' disease Diseases 0.000 claims description 3
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 3
- 201000004681 Psoriasis Diseases 0.000 claims description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
- 206010018634 Gouty Arthritis Diseases 0.000 claims description 2
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 2
- 208000024908 graft versus host disease Diseases 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 208000004296 neuralgia Diseases 0.000 claims description 2
- 208000021722 neuropathic pain Diseases 0.000 claims description 2
- 230000000737 periodic effect Effects 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 208000020408 systemic-onset juvenile idiopathic arthritis Diseases 0.000 claims description 2
- BPKHFMRIEPPQHW-UHFFFAOYSA-N 12-(6-methoxypyridin-3-yl)-3-[2-(trifluoromethoxy)phenyl]-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=CC=C1OC(F)(F)F BPKHFMRIEPPQHW-UHFFFAOYSA-N 0.000 claims 4
- RRMAYOKQWQYLHR-UHFFFAOYSA-N 3-(2-methoxy-5-methylphenyl)-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC(C)=CC=C1OC RRMAYOKQWQYLHR-UHFFFAOYSA-N 0.000 claims 4
- BKUKOKIJNVZIOU-UHFFFAOYSA-N 4-[5-[3-(2,5-dimethylphenyl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyrimidin-2-yl]morpholine Chemical compound CC1=CC=C(C)C(=C1)N1CCCC2=C1N1C=C(C=CC1=N2)C1=CN=C(N=C1)N1CCOCC1 BKUKOKIJNVZIOU-UHFFFAOYSA-N 0.000 claims 4
- MDOOVNVPGLCIQS-UHFFFAOYSA-N 11-chloro-3-[2-(difluoromethoxy)phenyl]-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1Cl)=NC1=C2N(CCC1)C1=CC=CC=C1OC(F)F MDOOVNVPGLCIQS-UHFFFAOYSA-N 0.000 claims 2
- GTKINMSFAALGIX-UHFFFAOYSA-N 12-(6-methoxypyridin-3-yl)-3-(2-methylphenyl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=CC=C1C GTKINMSFAALGIX-UHFFFAOYSA-N 0.000 claims 2
- YQCMHYPDMRJWAE-UHFFFAOYSA-N 12-(6-methoxypyridin-3-yl)-3-[2-methyl-5-(trifluoromethyl)phenyl]-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COc1ccc(cn1)-c1ccc2nc3CCCN(c3n2c1)c1cc(ccc1C)C(F)(F)F YQCMHYPDMRJWAE-UHFFFAOYSA-N 0.000 claims 2
- RAZXTCKOFLVXEW-UHFFFAOYSA-N 2-[4-[3-(2,5-dimethylphenyl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]phenyl]-5-methyl-1,3,4-oxadiazole Chemical compound CC1=NN=C(O1)C1=CC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC(C)=CC=C1C RAZXTCKOFLVXEW-UHFFFAOYSA-N 0.000 claims 2
- NJPSVZZOBISWPG-UHFFFAOYSA-N 2-[4-[3-(2,5-dimethylphenyl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]phenyl]propan-2-ol Chemical compound CC1=CC=C(C)C(=C1)N1CCCC2=C1N1C=C(C=CC1=N2)C1=CC=C(C=C1)C(C)(C)O NJPSVZZOBISWPG-UHFFFAOYSA-N 0.000 claims 2
- LRSSUODUVVLJMO-UHFFFAOYSA-N 2-[4-[3-[2-(difluoromethoxy)phenyl]-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]phenyl]-5-methyl-1,3,4-oxadiazole Chemical compound CC1=NN=C(O1)C1=CC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=CC=C1OC(F)F LRSSUODUVVLJMO-UHFFFAOYSA-N 0.000 claims 2
- LIAYRLHOEYLYRD-UHFFFAOYSA-N 2-[4-[3-[2-(difluoromethoxy)phenyl]-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]phenyl]propan-2-ol Chemical compound CC(C)(O)C1=CC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=CC=C1OC(F)F LIAYRLHOEYLYRD-UHFFFAOYSA-N 0.000 claims 2
- GZZJAUBTDCDPMJ-UHFFFAOYSA-N 2-[5-(11-chloro-3-phenyl-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl)pyrimidin-2-yl]propan-2-ol Chemical compound CC(C)(O)C1=NC=C(C=N1)C1=CN2C(C=C1Cl)=NC1=C2N(CCC1)C1=CC=CC=C1 GZZJAUBTDCDPMJ-UHFFFAOYSA-N 0.000 claims 2
- FAXFRALLHNUUQK-UHFFFAOYSA-N 2-[5-[3-(2,5-dimethylphenyl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound CC1=CC=C(C)C(=C1)N1CCCC2=C1N1C=C(C=CC1=N2)C1=CN=C(N=C1)C(C)(C)O FAXFRALLHNUUQK-UHFFFAOYSA-N 0.000 claims 2
- BXEVCQBRIJKBGK-UHFFFAOYSA-N 2-[5-[3-[2-(trifluoromethoxy)phenyl]-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound CC(C)(O)C1=NC=C(C=N1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=CC=C1OC(F)(F)F BXEVCQBRIJKBGK-UHFFFAOYSA-N 0.000 claims 2
- NEYWZSZKGWQPIT-UHFFFAOYSA-N 3-(2,3-dimethylphenyl)-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=CC(C)=C1C NEYWZSZKGWQPIT-UHFFFAOYSA-N 0.000 claims 2
- SJYAUOSFCWKCMA-UHFFFAOYSA-N 3-(2,5-dimethylphenyl)-11-methyl-12-(1-methylpyrazol-4-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound CN1C=C(C=N1)C1=CN2C(C=C1C)=NC1=C2N(CCC1)C1=CC(C)=CC=C1C SJYAUOSFCWKCMA-UHFFFAOYSA-N 0.000 claims 2
- ISNVPEHTFMANHQ-UHFFFAOYSA-N 3-(2,5-dimethylphenyl)-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC(C)=CC=C1C ISNVPEHTFMANHQ-UHFFFAOYSA-N 0.000 claims 2
- YELUGHHDAGMPFR-UHFFFAOYSA-N 3-(2,5-dimethylphenyl)-6-methyl-12-(1-methylpyrazol-4-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound CC1CCN(C2=C1N=C1C=CC(=CN21)C1=CN(C)N=C1)C1=CC(C)=CC=C1C YELUGHHDAGMPFR-UHFFFAOYSA-N 0.000 claims 2
- DXBLRWOOVQWASI-UHFFFAOYSA-N 3-(2-chlorophenyl)-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=CC=C1Cl DXBLRWOOVQWASI-UHFFFAOYSA-N 0.000 claims 2
- HGNACBVBFXXTOE-UHFFFAOYSA-N 3-(2-ethylphenyl)-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound CCC1=CC=CC=C1N1CCCC2=C1N1C=C(C=CC1=N2)C1=CN=C(OC)C=C1 HGNACBVBFXXTOE-UHFFFAOYSA-N 0.000 claims 2
- WSZVUMRAHWUBML-UHFFFAOYSA-N 3-(4-fluoro-2-methylphenyl)-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=C(F)C=C1C WSZVUMRAHWUBML-UHFFFAOYSA-N 0.000 claims 2
- QMJSYAYVXHPGHF-UHFFFAOYSA-N 3-(5-chloro-2-methylphenyl)-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC(Cl)=CC=C1C QMJSYAYVXHPGHF-UHFFFAOYSA-N 0.000 claims 2
- JJOQVANVLCVTHX-UHFFFAOYSA-N 3-(5-fluoro-2-methylphenyl)-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC(F)=CC=C1C JJOQVANVLCVTHX-UHFFFAOYSA-N 0.000 claims 2
- OBNJCHVJXDESNR-UHFFFAOYSA-N 3-[2-(difluoromethoxy)-5-methylphenyl]-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC(C)=CC=C1OC(F)F OBNJCHVJXDESNR-UHFFFAOYSA-N 0.000 claims 2
- YUJVHZBMQPZPBW-UHFFFAOYSA-N 3-[2-(difluoromethoxy)phenyl]-11-methyl-12-(1-methylpyrazol-4-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound CN1C=C(C=N1)C1=CN2C(C=C1C)=NC1=C2N(CCC1)C1=CC=CC=C1OC(F)F YUJVHZBMQPZPBW-UHFFFAOYSA-N 0.000 claims 2
- WAKBDVCYVKBZOR-UHFFFAOYSA-N 3-[2-(difluoromethoxy)phenyl]-12-(1-methylpyrazol-4-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound CN1C=C(C=N1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=CC=C1OC(F)F WAKBDVCYVKBZOR-UHFFFAOYSA-N 0.000 claims 2
- YJHNEWLMWIYRLL-UHFFFAOYSA-N 3-[2-(difluoromethoxy)phenyl]-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=CC=CC=C1OC(F)F YJHNEWLMWIYRLL-UHFFFAOYSA-N 0.000 claims 2
- DCGGMEVQFCHRNX-UHFFFAOYSA-N 3-[2-(difluoromethoxy)phenyl]-6-methyl-12-(1-methylpyrazol-4-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound CC1CCN(C2=C1N=C1C=CC(=CN21)C1=CN(C)N=C1)C1=CC=CC=C1OC(F)F DCGGMEVQFCHRNX-UHFFFAOYSA-N 0.000 claims 2
- YYNXSHZSOQSTRL-UHFFFAOYSA-N 3-isoquinolin-1-yl-12-(6-methoxypyridin-3-yl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraene Chemical compound COC1=NC=C(C=C1)C1=CN2C(C=C1)=NC1=C2N(CCC1)C1=NC=CC2=C1C=CC=C2 YYNXSHZSOQSTRL-UHFFFAOYSA-N 0.000 claims 2
- CMRXGVMEQDEAGO-UHFFFAOYSA-N 4-[5-[3-[2-(difluoromethoxy)-5-methylphenyl]-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyrimidin-2-yl]morpholine Chemical compound CC1=CC=C(OC(F)F)C(=C1)N1CCCC2=C1N1C=C(C=CC1=N2)C1=CN=C(N=C1)N1CCOCC1 CMRXGVMEQDEAGO-UHFFFAOYSA-N 0.000 claims 2
- VPZUJTMGMASNDY-UHFFFAOYSA-N 4-[5-[3-[2-(difluoromethoxy)phenyl]-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyrimidin-2-yl]morpholine Chemical compound FC(F)OC1=CC=CC=C1N1CCCC2=C1N1C=C(C=CC1=N2)C1=CN=C(N=C1)N1CCOCC1 VPZUJTMGMASNDY-UHFFFAOYSA-N 0.000 claims 2
- ZHIWKGWNUSQWDP-UHFFFAOYSA-N [5-[3-(2,5-dimethylphenyl)-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyridin-2-yl]methanol Chemical compound CC1=CC=C(C)C(=C1)N1CCCC2=C1N1C=C(C=CC1=N2)C1=CN=C(CO)C=C1 ZHIWKGWNUSQWDP-UHFFFAOYSA-N 0.000 claims 2
- WWYOIRSSYXRFBJ-UHFFFAOYSA-N [5-[3-(2,5-dimethylphenyl)-11-methyl-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyridin-2-yl]methanol Chemical compound CC1=CC=C(C)C(=C1)N1CCCC2=C1N1C=C(C(C)=CC1=N2)C1=CN=C(CO)C=C1 WWYOIRSSYXRFBJ-UHFFFAOYSA-N 0.000 claims 2
- SGNASRIYHOLKCO-UHFFFAOYSA-N [5-[3-(2,5-dimethylphenyl)-6-methyl-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyridin-2-yl]methanol Chemical compound CC1CCN(C2=C1N=C1C=CC(=CN21)C1=CN=C(CO)C=C1)C1=CC(C)=CC=C1C SGNASRIYHOLKCO-UHFFFAOYSA-N 0.000 claims 2
- SMFCQKJYSAWDPR-UHFFFAOYSA-N [5-[3-[2-(difluoromethoxy)phenyl]-11-methyl-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyridin-2-yl]methanol Chemical compound CC1=CC2=NC3=C(N2C=C1C1=CN=C(CO)C=C1)N(CCC3)C1=CC=CC=C1OC(F)F SMFCQKJYSAWDPR-UHFFFAOYSA-N 0.000 claims 2
- FEXOVFADEOBNJT-UHFFFAOYSA-N [5-[6-methyl-3-[2-(trifluoromethoxy)phenyl]-1,3,8-triazatricyclo[7.4.0.02,7]trideca-2(7),8,10,12-tetraen-12-yl]pyridin-2-yl]methanol Chemical compound CC1CCN(C2=C1N=C1C=CC(=CN21)C1=CN=C(CO)C=C1)C1=CC=CC=C1OC(F)(F)F FEXOVFADEOBNJT-UHFFFAOYSA-N 0.000 claims 2
- 125000002015 acyclic group Chemical group 0.000 claims 1
- IISBACLAFKSPIT-UHFFFAOYSA-N bisphenol A Chemical compound C=1C=C(O)C=CC=1C(C)(C)C1=CC=C(O)C=C1 IISBACLAFKSPIT-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 131
- 108700012920 TNF Proteins 0.000 abstract description 27
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 92
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 90
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- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
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- 201000000498 stomach carcinoma Diseases 0.000 description 1
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- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 239000011593 sulfur Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- SOJRRCWSZXYEQN-UHFFFAOYSA-N tert-butyl 4-methyl-3-oxopiperidine-1-carboxylate Chemical compound CC1CCN(C(=O)OC(C)(C)C)CC1=O SOJRRCWSZXYEQN-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
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- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
- 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 206010043778 thyroiditis Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Neurology (AREA)
- Physical Education & Sports Medicine (AREA)
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- Biomedical Technology (AREA)
- Communicable Diseases (AREA)
- Diabetes (AREA)
- Transplantation (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epidemiology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562134800P | 2015-03-18 | 2015-03-18 | |
| US62/134,800 | 2015-03-18 | ||
| PCT/US2016/022742 WO2016149439A1 (en) | 2015-03-18 | 2016-03-17 | Heterocyclic compounds useful as inhibitors of tnf |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2980161A1 true CA2980161A1 (en) | 2016-09-22 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2980161A Abandoned CA2980161A1 (en) | 2015-03-18 | 2016-03-17 | Heterocyclic compounds useful as inhibitors of tnf |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US10112944B2 (OSRAM) |
| EP (1) | EP3271362B1 (OSRAM) |
| JP (1) | JP6779899B2 (OSRAM) |
| KR (1) | KR102696304B1 (OSRAM) |
| CN (1) | CN107567450B (OSRAM) |
| AU (1) | AU2016233202A1 (OSRAM) |
| BR (1) | BR112017019605A2 (OSRAM) |
| CA (1) | CA2980161A1 (OSRAM) |
| EA (1) | EA201792054A1 (OSRAM) |
| ES (1) | ES2803650T3 (OSRAM) |
| IL (1) | IL254430A0 (OSRAM) |
| MX (1) | MX2017011577A (OSRAM) |
| SG (1) | SG11201707473VA (OSRAM) |
| WO (1) | WO2016149439A1 (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2797685T3 (es) | 2015-03-18 | 2020-12-03 | Bristol Myers Squibb Co | Compuestos heterocíclicos tricíclicos útiles como inhibidores de TNF |
| EA032315B1 (ru) | 2015-03-18 | 2019-05-31 | Бристол-Маерс Сквибб Компани | Замещенные трициклические гетероциклические соединения |
| AR104293A1 (es) | 2015-04-17 | 2017-07-12 | Abbvie Inc | Indazolonas como moduladores de la señalización de tnf |
| US9856253B2 (en) | 2015-04-17 | 2018-01-02 | Abbvie, Inc. | Tricyclic modulators of TNF signaling |
| US20160304496A1 (en) | 2015-04-17 | 2016-10-20 | Abbvie Inc. | Indazolones as modulators of tnf signaling |
| GB201510758D0 (en) | 2015-06-18 | 2015-08-05 | Ucb Biopharma Sprl | Novel TNFa structure for use in therapy |
| CN108137609B (zh) | 2015-08-03 | 2021-07-16 | 百时美施贵宝公司 | 用作TNFα的调节剂的环状化合物 |
| GB201621907D0 (en) | 2016-12-21 | 2017-02-01 | Ucb Biopharma Sprl And Sanofi | Antibody epitope |
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| US4391806A (en) * | 1982-07-12 | 1983-07-05 | The Dow Chemical Company | Substituted tetrahydropyridazino-(1,6-A)benzimidazoles and use as bronchodilators |
| AU741772B2 (en) | 1997-02-25 | 2001-12-06 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Substituted benzimidazoles as non-nucleoside inhibitors of reverse transcriptase |
| JPWO2003064422A1 (ja) | 2002-01-31 | 2005-05-26 | 第一製薬株式会社 | イミダゾ［１，２−ａ］ピリジン誘導体 |
| AU2003298839A1 (en) | 2002-12-03 | 2004-06-23 | Isis Pharmaceuticals, Inc. | Benzimidazoles and analogs thereof as antivirals |
| US20050124638A1 (en) | 2003-12-08 | 2005-06-09 | Swayze Eric E. | Benzimidazoles and analogs thereof as antivirals |
| WO2008072682A1 (ja) * | 2006-12-15 | 2008-06-19 | Daiichi Sankyo Company, Limited | イミダゾ［１，２－ｂ］ピリダジン誘導体 |
| WO2009045174A1 (en) | 2007-10-05 | 2009-04-09 | S*Bio Pte Ltd | 2-morpholinylpurines as inhibitors of pi3k |
| JP2009227599A (ja) | 2008-03-21 | 2009-10-08 | Daiichi Sankyo Co Ltd | イミダゾピリダジン誘導体 |
| CN101717397B (zh) | 2008-10-09 | 2012-11-28 | 中国科学院上海药物研究所 | 一类取代吡啶并[2',1':2,3]咪唑并[4,5-c]异喹啉酮类化合物及其合成方法和用途,以及包含该类化合物的药物组合物 |
| US8691187B2 (en) | 2009-03-23 | 2014-04-08 | Eli Lilly And Company | Imaging agents for detecting neurological disorders |
| WO2012148550A1 (en) | 2011-02-25 | 2012-11-01 | Myrexis, Inc. | Prodrugs of therapeutic compounds |
| EP2527344A1 (en) | 2011-05-25 | 2012-11-28 | Almirall, S.A. | Pyridin-2(1H)-one derivatives useful as medicaments for the treatment of myeloproliferative disorders, transplant rejection, immune-mediated and inflammatory diseases |
| TR201807207T4 (tr) * | 2012-06-11 | 2018-06-21 | Ucb Biopharma Sprl | Tnf-alfa modüle edici benzimidazol bileşikleri. |
| GB201212513D0 (en) | 2012-07-13 | 2012-08-29 | Ucb Pharma Sa | Therapeutic agents |
| CN104619709B (zh) * | 2012-07-13 | 2016-11-09 | Ucb生物制药私人有限公司 | 作为tnf活性调节剂的咪唑并吡啶衍生物 |
| BR112015009649A2 (pt) * | 2012-11-07 | 2017-07-04 | Hoffmann La Roche | composto de triazolo |
| WO2014080241A1 (en) * | 2012-11-21 | 2014-05-30 | Piramal Enterprises Limited | Imidazopyridine compounds and uses thereof |
| WO2015008611A1 (ja) | 2013-07-18 | 2015-01-22 | 株式会社 村田製作所 | 積層型インダクタ素子の製造方法 |
| GB201321746D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321741D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321737D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| GB201321743D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321742D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321744D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321735D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| GB201321738D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| BR112016013018A2 (pt) | 2013-12-09 | 2017-08-08 | Ucb Biopharma Sprl | Derivados heteroaromáticos bicíclicos fundidos como moduladores de atividade de tnf |
| GB201321739D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| RU2695664C1 (ru) | 2013-12-09 | 2019-07-25 | Юсб Байофарма Спрл | Производные имидазопиридина в качестве модуляторов активности tnf |
| CN113248506A (zh) | 2014-10-06 | 2021-08-13 | 西格诺药品有限公司 | 取代的氨基嘌呤化合物、其组合物及其治疗方法 |
| ES2797685T3 (es) | 2015-03-18 | 2020-12-03 | Bristol Myers Squibb Co | Compuestos heterocíclicos tricíclicos útiles como inhibidores de TNF |
| EA032315B1 (ru) | 2015-03-18 | 2019-05-31 | Бристол-Маерс Сквибб Компани | Замещенные трициклические гетероциклические соединения |
-
2016
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- 2016-03-17 ES ES16712647T patent/ES2803650T3/es active Active
- 2016-03-17 AU AU2016233202A patent/AU2016233202A1/en not_active Abandoned
- 2016-03-17 SG SG11201707473VA patent/SG11201707473VA/en unknown
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- 2016-03-17 JP JP2017548855A patent/JP6779899B2/ja active Active
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Also Published As
| Publication number | Publication date |
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| US20180072728A1 (en) | 2018-03-15 |
| BR112017019605A2 (pt) | 2018-05-08 |
| IL254430A0 (en) | 2017-11-30 |
| EP3271362A1 (en) | 2018-01-24 |
| KR102696304B1 (ko) | 2024-08-16 |
| ES2803650T3 (es) | 2021-01-28 |
| EA201792054A1 (ru) | 2018-01-31 |
| SG11201707473VA (en) | 2017-10-30 |
| CN107567450B (zh) | 2020-03-13 |
| CN107567450A (zh) | 2018-01-09 |
| JP2018512062A (ja) | 2018-05-10 |
| AU2016233202A1 (en) | 2017-11-09 |
| JP6779899B2 (ja) | 2020-11-04 |
| US10112944B2 (en) | 2018-10-30 |
| WO2016149439A1 (en) | 2016-09-22 |
| KR20170129192A (ko) | 2017-11-24 |
| EP3271362B1 (en) | 2020-04-22 |
| MX2017011577A (es) | 2017-10-26 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20220301 |