ES2803650T3 - Compuestos heterocíclicos útiles como inhibidores de TNF - Google Patents
Compuestos heterocíclicos útiles como inhibidores de TNF Download PDFInfo
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- ES2803650T3 ES2803650T3 ES16712647T ES16712647T ES2803650T3 ES 2803650 T3 ES2803650 T3 ES 2803650T3 ES 16712647 T ES16712647 T ES 16712647T ES 16712647 T ES16712647 T ES 16712647T ES 2803650 T3 ES2803650 T3 ES 2803650T3
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- aryl
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- 150000002391 heterocyclic compounds Chemical class 0.000 title description 6
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 title description 2
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 285
- -1 -OH Chemical group 0.000 claims abstract description 176
- 125000003118 aryl group Chemical group 0.000 claims abstract description 138
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 109
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 94
- 239000012453 solvate Substances 0.000 claims abstract description 81
- 150000003839 salts Chemical class 0.000 claims abstract description 74
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 68
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 44
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 37
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
- 125000005843 halogen group Chemical group 0.000 claims abstract description 27
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 21
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 19
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 15
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 13
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 11
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 11
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 10
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 9
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims abstract description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 4
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 3
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims abstract description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 20
- 208000023275 Autoimmune disease Diseases 0.000 claims description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 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 description 15
- 230000002757 inflammatory effect Effects 0.000 claims description 15
- 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 description 13
- 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 description 13
- 208000027866 inflammatory disease Diseases 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 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 description 8
- 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 description 8
- 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 description 8
- 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 description 8
- 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 description 8
- 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 description 7
- 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 description 7
- 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 description 7
- SSOYJIBODDUEBN-UHFFFAOYSA-N 3-(2,4-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(C)C=C1C SSOYJIBODDUEBN-UHFFFAOYSA-N 0.000 claims description 7
- 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 description 7
- 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 description 7
- 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 description 7
- 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 description 7
- 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 description 7
- 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 description 7
- 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 description 7
- 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 description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
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- 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 description 6
- 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 description 6
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- 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 description 4
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Classifications
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- 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
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Applications Claiming Priority (2)
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| US201562134800P | 2015-03-18 | 2015-03-18 | |
| PCT/US2016/022742 WO2016149439A1 (en) | 2015-03-18 | 2016-03-17 | Heterocyclic compounds useful as inhibitors of tnf |
Publications (1)
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| ES2803650T3 true ES2803650T3 (es) | 2021-01-28 |
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| ES16712647T Active ES2803650T3 (es) | 2015-03-18 | 2016-03-17 | Compuestos heterocíclicos útiles como inhibidores de TNF |
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|---|---|
| US (1) | US10112944B2 (enExample) |
| EP (1) | EP3271362B1 (enExample) |
| JP (1) | JP6779899B2 (enExample) |
| KR (1) | KR102696304B1 (enExample) |
| CN (1) | CN107567450B (enExample) |
| AU (1) | AU2016233202A1 (enExample) |
| BR (1) | BR112017019605A2 (enExample) |
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| EA (1) | EA201792054A1 (enExample) |
| ES (1) | ES2803650T3 (enExample) |
| IL (1) | IL254430A0 (enExample) |
| MX (1) | MX2017011577A (enExample) |
| SG (1) | SG11201707473VA (enExample) |
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| AU2016233288A1 (en) | 2015-03-18 | 2017-11-09 | Bristol-Myers Squibb Company | Substituted tricyclic heterocyclic compounds |
| US9879016B2 (en) | 2015-04-17 | 2018-01-30 | 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 |
| 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 |
| KR102679517B1 (ko) | 2015-08-03 | 2024-06-27 | 브리스톨-마이어스 스큅 컴퍼니 | Tnf 알파의 조정제로서 유용한 시클릭 화합물 |
| GB201621907D0 (en) | 2016-12-21 | 2017-02-01 | Ucb Biopharma Sprl And Sanofi | Antibody epitope |
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| 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 |
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| 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 |
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| 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 |
| BR112014030940B1 (pt) | 2012-06-11 | 2022-09-06 | UCB Biopharma SRL | Benzimidazóis que modulam tnf-alfa e composição farmacêutica compreendendo os mesmos |
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| 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 |
| CN104768554B (zh) * | 2012-11-07 | 2018-04-17 | 霍夫曼-拉罗奇有限公司 | 三唑并化合物 |
| 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 |
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| US9512124B2 (en) | 2014-10-06 | 2016-12-06 | Signal Pharmaceuticals, Llc | Substituted aminopurine compounds, compositions thereof, and methods of treatment therewith |
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- 2016-03-17 US US15/558,724 patent/US10112944B2/en active Active
- 2016-03-17 CN CN201680026732.5A patent/CN107567450B/zh active Active
- 2016-03-17 CA CA2980161A patent/CA2980161A1/en not_active Abandoned
- 2016-03-17 WO PCT/US2016/022742 patent/WO2016149439A1/en not_active Ceased
- 2016-03-17 SG SG11201707473VA patent/SG11201707473VA/en unknown
- 2016-03-17 AU AU2016233202A patent/AU2016233202A1/en not_active Abandoned
- 2016-03-17 ES ES16712647T patent/ES2803650T3/es active Active
- 2016-03-17 KR KR1020177029451A patent/KR102696304B1/ko active Active
- 2016-03-17 BR BR112017019605A patent/BR112017019605A2/pt not_active Application Discontinuation
- 2016-03-17 EA EA201792054A patent/EA201792054A1/ru unknown
- 2016-03-17 JP JP2017548855A patent/JP6779899B2/ja active Active
-
2017
- 2017-09-11 IL IL254430A patent/IL254430A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EA201792054A1 (ru) | 2018-01-31 |
| EP3271362A1 (en) | 2018-01-24 |
| AU2016233202A1 (en) | 2017-11-09 |
| CA2980161A1 (en) | 2016-09-22 |
| SG11201707473VA (en) | 2017-10-30 |
| IL254430A0 (en) | 2017-11-30 |
| US10112944B2 (en) | 2018-10-30 |
| KR102696304B1 (ko) | 2024-08-16 |
| CN107567450B (zh) | 2020-03-13 |
| BR112017019605A2 (pt) | 2018-05-08 |
| CN107567450A (zh) | 2018-01-09 |
| EP3271362B1 (en) | 2020-04-22 |
| JP6779899B2 (ja) | 2020-11-04 |
| WO2016149439A1 (en) | 2016-09-22 |
| KR20170129192A (ko) | 2017-11-24 |
| JP2018512062A (ja) | 2018-05-10 |
| US20180072728A1 (en) | 2018-03-15 |
| MX2017011577A (es) | 2017-10-26 |
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