CA2994703A1 - Cyclic compounds useful as modulators of tnf alpha - Google Patents
Cyclic compounds useful as modulators of tnf alpha Download PDFInfo
- Publication number
- CA2994703A1 CA2994703A1 CA2994703A CA2994703A CA2994703A1 CA 2994703 A1 CA2994703 A1 CA 2994703A1 CA 2994703 A CA2994703 A CA 2994703A CA 2994703 A CA2994703 A CA 2994703A CA 2994703 A1 CA2994703 A1 CA 2994703A1
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- Prior art keywords
- zero
- alkyl
- substituted
- phenyl
- pyrrolo
- 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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- 150000001923 cyclic compounds Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 285
- 150000003839 salts Chemical class 0.000 claims abstract description 75
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 74
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 27
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 20
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 18
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 13
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims abstract description 6
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 206
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 100
- -1 -OH Chemical group 0.000 claims description 85
- 125000002950 monocyclic group Chemical group 0.000 claims description 85
- 125000003118 aryl group Chemical group 0.000 claims description 78
- 125000000217 alkyl group Chemical group 0.000 claims description 69
- 239000000203 mixture Substances 0.000 claims description 66
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 61
- 229910052731 fluorine Inorganic materials 0.000 claims description 40
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 40
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 38
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 30
- 229910052801 chlorine Inorganic materials 0.000 claims description 30
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims description 27
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 26
- IIOKDOJKJGCOEP-UHFFFAOYSA-N 3h-pyrrolo[1,2-a]imidazole Chemical compound C1=CN2CC=NC2=C1 IIOKDOJKJGCOEP-UHFFFAOYSA-N 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000005843 halogen group Chemical group 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 22
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 21
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 20
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 19
- 229910052794 bromium Inorganic materials 0.000 claims description 18
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000005605 benzo group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 9
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 9
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 239000003085 diluting agent Substances 0.000 claims description 7
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 5
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 4
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 4
- 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 102000003298 tumor necrosis factor receptor Human genes 0.000 claims description 4
- 208000023328 Basedow disease Diseases 0.000 claims description 3
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 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
- 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
- 125000001054 5 membered carbocyclic 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
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 2
- 125000001207 fluorophenyl group Chemical group 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
- DSEWTWHQTAWRCR-XFQAVAEZSA-N 2-[5-[(3R,4R,6S)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@H]2[C@@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)C(C)(C)O)F)C2)F DSEWTWHQTAWRCR-XFQAVAEZSA-N 0.000 claims 4
- BJEMFFWEUUXDTP-IEVXNVSRSA-N (3R,4S,6R)-12-bromo-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(13),7,9,11-tetraene Chemical compound BrC1=CC2=C(N=C3N2[C@H]([C@@H]2[C@H]3C2)C2=C(C=CC=C2)OC(F)F)C=C1F BJEMFFWEUUXDTP-IEVXNVSRSA-N 0.000 claims 2
- ZMXXUTYAIDYCHN-TYBLODHISA-N 1-[(10R,14S,15S)-4-(6-methoxypyridin-3-yl)-15-phenyl-1,8,12-triazatetracyclo[7.6.0.02,7.010,14]pentadeca-2(7),3,5,8-tetraen-12-yl]ethanone Chemical compound COC1=CC=C(C=N1)C1=CC2=C(N=C3N2[C@@H]([C@H]2[C@@H]3CN(C2)C(C)=O)C2=CC=CC=C2)C=C1 ZMXXUTYAIDYCHN-TYBLODHISA-N 0.000 claims 2
- ZWWMMUMETQYJQW-JKSBSHDWSA-N 1-[4-[(3R,4S,6R)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrazol-1-yl]-2-methylpropan-2-ol Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@@H]2[C@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NN(C=1)CC(C)(O)C)F)C2)F ZWWMMUMETQYJQW-JKSBSHDWSA-N 0.000 claims 2
- HRDJBRDUCRJPQF-GLDPYIMESA-N 2-[4-[(3R,4S,6R)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]phenyl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@@H]2[C@H](C=3N1C1=C(N=3)C=C(C(=C1)C1=CC=C(C=C1)C(C)(C)O)F)C2)F HRDJBRDUCRJPQF-GLDPYIMESA-N 0.000 claims 2
- OOFCGIVGOQCKFA-HHJKRLRDSA-N 2-[4-[5-[(3S,4R,6S)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]piperazin-1-yl]acetic acid Chemical compound FC(OC1=C(C=CC=C1)[C@@H]1[C@H]2[C@@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)N1CCN(CC1)CC(=O)O)F)C2)F OOFCGIVGOQCKFA-HHJKRLRDSA-N 0.000 claims 2
- JPFAOFJABONAJB-VHSZZVNMSA-N 2-[5-[(3R,4R,6S)-11-fluoro-3-(2-phenoxyphenyl)-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC=1C(=CC2=C(N=C3N2[C@H]([C@H]2[C@@H]3C2)C2=C(C=CC=C2)OC2=CC=CC=C2)C=1)C=1C=NC(=NC=1)C(C)(C)O JPFAOFJABONAJB-VHSZZVNMSA-N 0.000 claims 2
- JIQGOPATCHHCIY-JVAFGIKQSA-N 2-[5-[(3R,4R,6S)-11-fluoro-3-[2-(2-fluorophenoxy)phenyl]-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC=1C(=CC2=C(N=C3N2[C@H]([C@H]2[C@@H]3C2)C2=C(C=CC=C2)OC2=C(C=CC=C2)F)C=1)C=1C=NC(=NC=1)C(C)(C)O JIQGOPATCHHCIY-JVAFGIKQSA-N 0.000 claims 2
- SMBWSTQAPWTKBN-VHSZZVNMSA-N 2-[5-[(3R,4R,6S)-11-fluoro-3-[2-(pyridin-4-ylmethoxy)phenyl]-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC=1C(=CC2=C(N=C3N2[C@H]([C@H]2[C@@H]3C2)C2=C(C=CC=C2)OCC2=CC=NC=C2)C=1)C=1C=NC(=NC=1)C(C)(C)O SMBWSTQAPWTKBN-VHSZZVNMSA-N 0.000 claims 2
- JPFAOFJABONAJB-XXAUWVGASA-N 2-[5-[(3R,4S,6R)-11-fluoro-3-(2-phenoxyphenyl)-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC=1C(=CC2=C(N=C3N2[C@H]([C@@H]2[C@H]3C2)C2=C(C=CC=C2)OC2=CC=CC=C2)C=1)C=1C=NC(=NC=1)C(C)(C)O JPFAOFJABONAJB-XXAUWVGASA-N 0.000 claims 2
- ZEUSMNCNQXELPK-JWZKTCGFSA-N 2-[5-[(3R,4S,6R)-11-fluoro-3-(2-phenylmethoxyphenyl)-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound C(C1=CC=CC=C1)OC1=C(C=CC=C1)[C@H]1[C@@H]2[C@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)C(C)(C)O)F)C2 ZEUSMNCNQXELPK-JWZKTCGFSA-N 0.000 claims 2
- KPSZBWZVNHDONM-MFEFFIJZSA-N 2-[5-[(3R,4S,6R)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyridin-2-yl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@@H]2[C@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=CC(=NC=1)C(C)(C)O)F)C2)F KPSZBWZVNHDONM-MFEFFIJZSA-N 0.000 claims 2
- DSEWTWHQTAWRCR-MRUHUIDDSA-N 2-[5-[(3R,4S,6R)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@@H]2[C@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)C(C)(C)O)F)C2)F DSEWTWHQTAWRCR-MRUHUIDDSA-N 0.000 claims 2
- JPFAOFJABONAJB-UMTXDNHDSA-N 2-[5-[(3S,4R,6S)-11-fluoro-3-(2-phenoxyphenyl)-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC=1C(=CC2=C(N=C3N2[C@@H]([C@H]2[C@@H]3C2)C2=C(C=CC=C2)OC2=CC=CC=C2)C=1)C=1C=NC(=NC=1)C(C)(C)O JPFAOFJABONAJB-UMTXDNHDSA-N 0.000 claims 2
- JIQGOPATCHHCIY-IOKPGSKQSA-N 2-[5-[(3S,4R,6S)-11-fluoro-3-[2-(2-fluorophenoxy)phenyl]-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC=1C(=CC2=C(N=C3N2[C@@H]([C@H]2[C@@H]3C2)C2=C(C=CC=C2)OC2=C(C=CC=C2)F)C=1)C=1C=NC(=NC=1)C(C)(C)O JIQGOPATCHHCIY-IOKPGSKQSA-N 0.000 claims 2
- SMBWSTQAPWTKBN-UMTXDNHDSA-N 2-[5-[(3S,4R,6S)-11-fluoro-3-[2-(pyridin-4-ylmethoxy)phenyl]-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC=1C(=CC2=C(N=C3N2[C@@H]([C@H]2[C@@H]3C2)C2=C(C=CC=C2)OCC2=CC=NC=C2)C=1)C=1C=NC(=NC=1)C(C)(C)O SMBWSTQAPWTKBN-UMTXDNHDSA-N 0.000 claims 2
- DSEWTWHQTAWRCR-VWKPWSFCSA-N 2-[5-[(3S,4R,6S)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound FC(OC1=C(C=CC=C1)[C@@H]1[C@H]2[C@@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)C(C)(C)O)F)C2)F DSEWTWHQTAWRCR-VWKPWSFCSA-N 0.000 claims 2
- ZEUSMNCNQXELPK-SXDGJLEOSA-N 2-[5-[(3S,4S,6R)-11-fluoro-3-(2-phenylmethoxyphenyl)-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound C(C1=CC=CC=C1)OC1=C(C=CC=C1)[C@@H]1[C@@H]2[C@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)C(C)(C)O)F)C2 ZEUSMNCNQXELPK-SXDGJLEOSA-N 0.000 claims 2
- DSEWTWHQTAWRCR-UHFFFAOYSA-N 2-[5-[3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]propan-2-ol Chemical compound CC(C)(C1=NC=C(C=N1)C2=CC3=C(C=C2F)N=C4N3C(C5C4C5)C6=CC=CC=C6OC(F)F)O DSEWTWHQTAWRCR-UHFFFAOYSA-N 0.000 claims 2
- WIHPGSLLVUIVNA-MRUHUIDDSA-N 3-[5-[(3R,4S,6R)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]oxetan-3-ol Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@@H]2[C@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)C1(COC1)O)F)C2)F WIHPGSLLVUIVNA-MRUHUIDDSA-N 0.000 claims 2
- KNIBARYIKQDQLT-STSQHVNTSA-N 4-[5-[(3R,4R,6S)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]morpholine Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@H]2[C@@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)N1CCOCC1)F)C2)F KNIBARYIKQDQLT-STSQHVNTSA-N 0.000 claims 2
- MNIYJLHJHQTSEE-MFEFFIJZSA-N 4-[5-[(3R,4S,6R)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]piperazin-2-one Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@@H]2[C@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)N1CC(NCC1)=O)F)C2)F MNIYJLHJHQTSEE-MFEFFIJZSA-N 0.000 claims 2
- KNIBARYIKQDQLT-IEGUWTFLSA-N 4-[5-[(3S,4R,6S)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyrimidin-2-yl]morpholine Chemical compound FC(OC1=C(C=CC=C1)[C@@H]1[C@H]2[C@@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=NC(=NC=1)N1CCOCC1)F)C2)F KNIBARYIKQDQLT-IEGUWTFLSA-N 0.000 claims 2
- QUUPVBOIUYQRLI-WIEQDCTASA-N 5-[(3R,4R,6S)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]pyridine-2-carboxamide Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@H]2[C@@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=CC(=NC=1)C(=O)N)F)C2)F QUUPVBOIUYQRLI-WIEQDCTASA-N 0.000 claims 2
- UYWCYWQJCZVXOE-DMPWYTOCSA-N 5-[(3R,4S,6R)-3-[2-(difluoromethoxy)phenyl]-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(9),7,10,12-tetraen-12-yl]-N-methylpyridine-2-carboxamide Chemical compound FC(OC1=C(C=CC=C1)[C@H]1[C@@H]2[C@H](C=3N1C1=C(N=3)C=C(C(=C1)C=1C=CC(=NC=1)C(=O)NC)F)C2)F UYWCYWQJCZVXOE-DMPWYTOCSA-N 0.000 claims 2
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562200415P | 2015-08-03 | 2015-08-03 | |
| US62/200,415 | 2015-08-03 | ||
| PCT/US2016/045104 WO2017023902A1 (en) | 2015-08-03 | 2016-08-02 | Cyclic compounds useful as modulators of tnf alpha |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2994703A1 true CA2994703A1 (en) | 2017-02-09 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2994703A Abandoned CA2994703A1 (en) | 2015-08-03 | 2016-08-02 | Cyclic compounds useful as modulators of tnf alpha |
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| EP (1) | EP3331889B1 (enExample) |
| JP (1) | JP6811233B2 (enExample) |
| KR (1) | KR102679517B1 (enExample) |
| CN (1) | CN108137609B (enExample) |
| AU (1) | AU2016301215A1 (enExample) |
| BR (1) | BR112018001980A2 (enExample) |
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| IL (1) | IL257159A (enExample) |
| MX (1) | MX2018001173A (enExample) |
| WO (1) | WO2017023902A1 (enExample) |
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| UY36629A (es) | 2015-04-17 | 2016-11-30 | Abbvie Inc | Indazolonas como moduladores de la señalización de tnf |
| EP3286195A1 (en) | 2015-04-17 | 2018-02-28 | AbbVie Inc. | Indazolones as modulators of tnf signaling |
| AR104291A1 (es) | 2015-04-17 | 2017-07-12 | Abbvie Inc | Moduladores tricíclicos de la señalización por tnf |
| GB201510758D0 (en) | 2015-06-18 | 2015-08-05 | Ucb Biopharma Sprl | Novel TNFa structure for use in therapy |
| GB201621907D0 (en) | 2016-12-21 | 2017-02-01 | Ucb Biopharma Sprl And Sanofi | Antibody epitope |
| WO2021226208A2 (en) | 2020-05-05 | 2021-11-11 | Nuvalent, Inc. | Heteroaromatic macrocyclic ether chemotherapeutic agents |
| KR102698413B1 (ko) | 2020-05-05 | 2024-08-26 | 뉴베일런트, 아이엔씨. | 헤테로방향족 거대환식 에터 화학치료제 |
| TW202320768A (zh) | 2021-10-01 | 2023-06-01 | 美商努法倫特公司 | 雜芳族大環醚化合物之固體形式、醫藥組成物及製備 |
| KR20250051687A (ko) * | 2022-08-08 | 2025-04-17 | 메디노 파마슈티컬 테크놀로지 (주하이) 컴퍼니 리미티드 | TGF-β 억제제 화합물 및 그 사용 |
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| JPS5149386A (ja) * | 1974-10-28 | 1976-04-28 | Hitachi Ltd | Shuchukanshiseigyohoho |
| EP0963371B1 (en) | 1997-02-25 | 2003-05-02 | THE GOVERNMENT OF THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES | Substituted benzimidazoles as non-nucleoside inhibitors of reverse transcriptase |
| JPH11228539A (ja) * | 1997-12-03 | 1999-08-24 | Taisho Pharmaceut Co Ltd | 含窒素四環性化合物 |
| US7601846B2 (en) | 2001-06-26 | 2009-10-13 | The Regents Of The University Of California | Compounds having activity as inhibitors of apoptosis |
| CA2474850A1 (en) | 2002-01-31 | 2003-08-07 | Daiichi Pharmaceutical Co., Ltd. | Imidazo[1,2-a]pyridine derivatives |
| WO2004050035A2 (en) | 2002-12-03 | 2004-06-17 | 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 |
| EP2209785A1 (en) | 2007-10-05 | 2010-07-28 | 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 |
| CN102438660A (zh) | 2009-03-23 | 2012-05-02 | 美国西门子医疗解决公司 | 用于检测神经障碍的显像剂 |
| 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 |
| ES2689429T3 (es) | 2012-07-13 | 2018-11-14 | Ucb Biopharma Sprl | Derivados de imidazopiridina como moduladores de actividad de TNF |
| GB201212513D0 (en) | 2012-07-13 | 2012-08-29 | Ucb Pharma Sa | Therapeutic agents |
| KR101669334B1 (ko) * | 2013-09-30 | 2016-10-25 | 주식회사 엘지화학 | 헤테로환 화합물 및 이를 포함하는 유기 발광 소자 |
| GB201321738D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
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| US9815797B2 (en) | 2013-12-09 | 2017-11-14 | Ucb Biopharma Sprl | Fused bicyclic heteroaromatic derivatives as modulators of TNF activity |
| GB201321735D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| GB201321728D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
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| GB201321737D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| ES2809535T3 (es) | 2013-12-09 | 2021-03-04 | UCB Biopharma SRL | Derivados de imidazopiridina como moduladores de la actividad de TNF |
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| DK3204386T3 (da) | 2014-10-06 | 2021-05-25 | Signal Pharm Llc | Substituerede aminopurinforbindelser, sammensætninger deraf og fremgangsmåder til behandling dermed |
| US10112944B2 (en) | 2015-03-18 | 2018-10-30 | Bristol-Myers Squibb Company | Heterocyclic compounds useful as inhibitors of TNF |
| ES2797805T3 (es) | 2015-03-18 | 2020-12-03 | Bristol Myers Squibb Co | Compuestos heterocíclicos tricíclicos sustituidos |
| ES2797685T3 (es) | 2015-03-18 | 2020-12-03 | Bristol Myers Squibb Co | Compuestos heterocíclicos tricíclicos útiles como inhibidores de TNF |
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2016
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- 2016-08-02 CA CA2994703A patent/CA2994703A1/en not_active Abandoned
- 2016-08-02 BR BR112018001980A patent/BR112018001980A2/pt not_active Application Discontinuation
- 2016-08-02 AU AU2016301215A patent/AU2016301215A1/en not_active Abandoned
- 2016-08-02 MX MX2018001173A patent/MX2018001173A/es unknown
- 2016-08-02 EP EP16748045.8A patent/EP3331889B1/en active Active
- 2016-08-02 JP JP2018506125A patent/JP6811233B2/ja active Active
- 2016-08-02 US US15/749,611 patent/US10335392B2/en active Active
- 2016-08-02 KR KR1020187005708A patent/KR102679517B1/ko active Active
- 2016-08-02 WO PCT/US2016/045104 patent/WO2017023902A1/en not_active Ceased
- 2016-08-02 CN CN201680057965.1A patent/CN108137609B/zh active Active
- 2016-08-02 ES ES16748045T patent/ES2828696T3/es active Active
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2018
- 2018-01-25 IL IL257159A patent/IL257159A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20180031773A (ko) | 2018-03-28 |
| US20180221344A1 (en) | 2018-08-09 |
| ES2828696T3 (es) | 2021-05-27 |
| US10335392B2 (en) | 2019-07-02 |
| CN108137609A (zh) | 2018-06-08 |
| KR102679517B1 (ko) | 2024-06-27 |
| JP6811233B2 (ja) | 2021-01-13 |
| WO2017023902A1 (en) | 2017-02-09 |
| IL257159A (en) | 2018-03-29 |
| AU2016301215A1 (en) | 2018-03-22 |
| EP3331889B1 (en) | 2020-09-23 |
| JP2018525377A (ja) | 2018-09-06 |
| EA201890421A1 (ru) | 2018-07-31 |
| CN108137609B (zh) | 2021-07-16 |
| EP3331889A1 (en) | 2018-06-13 |
| MX2018001173A (es) | 2018-04-24 |
| BR112018001980A2 (pt) | 2018-09-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20200831 |