ES2828696T3 - Compuestos cíclicos útiles como moduladores de TNF alfa - Google Patents
Compuestos cíclicos útiles como moduladores de TNF alfa Download PDFInfo
- Publication number
- ES2828696T3 ES2828696T3 ES16748045T ES16748045T ES2828696T3 ES 2828696 T3 ES2828696 T3 ES 2828696T3 ES 16748045 T ES16748045 T ES 16748045T ES 16748045 T ES16748045 T ES 16748045T ES 2828696 T3 ES2828696 T3 ES 2828696T3
- Authority
- ES
- Spain
- Prior art keywords
- zero
- alkyl
- substituted
- heterocyclyl
- crgrg
- 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.)
- Active
Links
- 150000001923 cyclic compounds Chemical class 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 298
- 150000001875 compounds Chemical class 0.000 claims abstract description 282
- -1 -OH Chemical group 0.000 claims abstract description 203
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 180
- 125000003118 aryl group Chemical group 0.000 claims abstract description 136
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 104
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 95
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 87
- 150000003839 salts Chemical class 0.000 claims abstract description 75
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 72
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 61
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 57
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 45
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 39
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 34
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 33
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 33
- 125000005843 halogen group Chemical group 0.000 claims abstract description 33
- 125000003709 fluoroalkyl group Chemical group 0.000 claims abstract description 31
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 24
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract description 22
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 20
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 15
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 14
- 125000005605 benzo group Chemical group 0.000 claims abstract description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 12
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 10
- 125000004428 fluoroalkoxy group Chemical group 0.000 claims abstract description 8
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 8
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004429 atom Chemical group 0.000 claims abstract description 7
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 6
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims abstract description 6
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 6
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims abstract description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
- 125000006574 non-aromatic ring group Chemical group 0.000 claims abstract description 6
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 5
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims abstract description 5
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 5
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 4
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract 2
- 239000000203 mixture Substances 0.000 claims description 67
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 40
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 22
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 19
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 claims description 19
- 208000023275 Autoimmune disease Diseases 0.000 claims description 18
- 208000027866 inflammatory disease Diseases 0.000 claims description 16
- 230000002757 inflammatory effect Effects 0.000 claims description 13
- 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 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- VNALVOZUSICTIH-UHFFFAOYSA-N 6,9-diazatricyclo[4.3.0.02,4]nona-1(9),2,4,7-tetraene Chemical compound N1=C2N(C=C1)C=C1C2=C1 VNALVOZUSICTIH-UHFFFAOYSA-N 0.000 claims description 10
- 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 description 9
- SBZJQXFOZICKET-UHFFFAOYSA-N N1C=2N(C=C1C(=O)N)C=CC=2 Chemical compound N1C=2N(C=C1C(=O)N)C=CC=2 SBZJQXFOZICKET-UHFFFAOYSA-N 0.000 claims description 9
- 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 description 8
- 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 8
- 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 description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 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 description 6
- 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 description 6
- DDDWRDSBPPTAAS-UHFFFAOYSA-N 4-(6-methoxypyridin-3-yl)-15-phenyl-1,8,12-triazatetracyclo[7.6.0.02,7.010,14]pentadeca-2(7),3,5,8-tetraene Chemical compound COC1=CC=C(C=N1)C1=CC2=C(N=C3N2C(C2C3CNC2)C2=CC=CC=C2)C=C1 DDDWRDSBPPTAAS-UHFFFAOYSA-N 0.000 claims description 6
- QIJWWKSMZROLSE-JKSBSHDWSA-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]pyridine-2-carbonitrile 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#N)F)C2)F QIJWWKSMZROLSE-JKSBSHDWSA-N 0.000 claims description 6
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 6
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 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 description 4
- 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 description 4
- 201000005569 Gout Diseases 0.000 claims description 4
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 claims description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- QMLWSAXEQSBAAQ-UHFFFAOYSA-N oxetan-3-ol Chemical compound OC1COC1 QMLWSAXEQSBAAQ-UHFFFAOYSA-N 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
- 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 description 3
- 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 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
- 208000005777 Lupus Nephritis 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
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 3
- 230000000737 periodic effect Effects 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 208000011580 syndromic disease Diseases 0.000 claims description 3
- 230000009885 systemic effect Effects 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
- 208000026326 Adult-onset Still disease Diseases 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
- 208000003456 Juvenile Arthritis Diseases 0.000 claims description 2
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 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
- 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
- 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
- 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
- NACQRCDPSHHQPT-UHFFFAOYSA-N 8-(6-methoxypyridin-3-yl)-11-phenyl-4,4a,11,11a-tetrahydro-1H-isoindolo[2,1-a]benzimidazole Chemical compound COc1ccc(cn1)-c1ccc2nc3C4CC=CCC4C(c4ccccc4)n3c2c1 NACQRCDPSHHQPT-UHFFFAOYSA-N 0.000 claims 2
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims 2
- GXORCHFZBANVBV-GKIKGMKOSA-N 5-[(3S,4R,5R,6S)-3-(2,5-dimethylphenyl)-5-phenyl-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 CC1=C(C=C(C=C1)C)[C@@H]1[C@H]2[C@@H](C=3N1C1=C(N=3)C=CC(=C1)C=1C=CC(=NC=1)C(=O)NC)[C@@H]2C1=CC=CC=C1 GXORCHFZBANVBV-GKIKGMKOSA-N 0.000 claims 1
- 208000023328 Basedow disease Diseases 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 95
- 238000000034 method Methods 0.000 description 86
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 74
- 239000000543 intermediate Substances 0.000 description 68
- 235000002639 sodium chloride Nutrition 0.000 description 67
- 230000014759 maintenance of location Effects 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 46
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 42
- 239000000243 solution Substances 0.000 description 41
- 239000012071 phase Substances 0.000 description 38
- 235000019439 ethyl acetate Nutrition 0.000 description 32
- 238000003786 synthesis reaction Methods 0.000 description 30
- 230000015572 biosynthetic process Effects 0.000 description 28
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 28
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 27
- 150000001721 carbon Chemical group 0.000 description 23
- 239000000725 suspension Substances 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- 108700012920 TNF Proteins 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 22
- 239000007787 solid Substances 0.000 description 21
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 20
- 239000005695 Ammonium acetate Substances 0.000 description 19
- 235000019257 ammonium acetate Nutrition 0.000 description 19
- 229940043376 ammonium acetate Drugs 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 208000035475 disorder Diseases 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 238000004519 manufacturing process Methods 0.000 description 16
- 239000012453 solvate Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- 239000003814 drug Substances 0.000 description 13
- 125000001072 heteroaryl group Chemical group 0.000 description 13
- 239000002245 particle Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 12
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 229910052717 sulfur Inorganic materials 0.000 description 11
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000000463 material Substances 0.000 description 10
- 239000000546 pharmaceutical excipient Substances 0.000 description 10
- 238000004007 reversed phase HPLC Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 102100040247 Tumor necrosis factor Human genes 0.000 description 9
- 239000002671 adjuvant Substances 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000001363 autoimmune Effects 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- 239000003995 emulsifying agent Substances 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
- 239000013058 crude material Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 239000000796 flavoring agent Substances 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 239000003755 preservative agent Substances 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 208000024172 Cardiovascular disease Diseases 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 125000003342 alkenyl group Chemical group 0.000 description 7
- 125000000304 alkynyl group Chemical group 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 235000014113 dietary fatty acids Nutrition 0.000 description 7
- 239000000194 fatty acid Substances 0.000 description 7
- 229930195729 fatty acid Natural products 0.000 description 7
- 150000004665 fatty acids Chemical class 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000007170 pathology Effects 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000007900 aqueous suspension Substances 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 208000030159 metabolic disease Diseases 0.000 description 6
- 229920003023 plastic Polymers 0.000 description 6
- 239000004033 plastic Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- 239000000080 wetting agent Substances 0.000 description 6
- 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 description 5
- 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 description 5
- 229920000858 Cyclodextrin Polymers 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 208000012902 Nervous system disease Diseases 0.000 description 5
- 208000025966 Neurological disease Diseases 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 208000030533 eye disease Diseases 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 208000015122 neurodegenerative disease Diseases 0.000 description 5
- 230000000926 neurological effect Effects 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 230000036961 partial effect Effects 0.000 description 5
- 125000004193 piperazinyl group Chemical group 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 239000003381 stabilizer Substances 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical class CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- 125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 235000019483 Peanut oil Nutrition 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 125000002015 acyclic group Chemical group 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000000969 carrier Substances 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 235000019197 fats Nutrition 0.000 description 4
- 238000003818 flash chromatography Methods 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 150000002391 heterocyclic compounds Chemical class 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000000771 oncological effect Effects 0.000 description 4
- 239000000123 paper Substances 0.000 description 4
- 239000000312 peanut oil Substances 0.000 description 4
- 229920000728 polyester Polymers 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000002335 preservative effect Effects 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 125000003107 substituted aryl group Chemical group 0.000 description 4
- 125000004434 sulfur atom Chemical group 0.000 description 4
- 239000000375 suspending agent Substances 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- ZKFYXPBEHCTIIX-OVCLIPMQSA-N (NE)-N-[[2-(difluoromethoxy)phenyl]methylidene]-2-methylpropane-2-sulfinamide Chemical compound FC(OC1=C(\C=N\S(=O)C(C)(C)C)C=CC=C1)F ZKFYXPBEHCTIIX-OVCLIPMQSA-N 0.000 description 3
- RDSTUZNZEPFHCD-UHFFFAOYSA-N 1-[2-(difluoromethoxy)phenyl]prop-2-en-1-amine Chemical compound C=CC(N)C1=CC=CC=C1OC(F)F RDSTUZNZEPFHCD-UHFFFAOYSA-N 0.000 description 3
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- 206010018364 Glomerulonephritis Diseases 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
- 239000007832 Na2SO4 Substances 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 238000006161 Suzuki-Miyaura coupling reaction Methods 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 230000000172 allergic effect Effects 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 125000002837 carbocyclic group Chemical group 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 238000001023 centrifugal evaporation Methods 0.000 description 3
- 125000004965 chloroalkyl group Chemical group 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 230000005714 functional activity Effects 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- OWFXIOWLTKNBAP-UHFFFAOYSA-N isoamyl nitrite Chemical compound CC(C)CCON=O OWFXIOWLTKNBAP-UHFFFAOYSA-N 0.000 description 3
- 230000000366 juvenile effect Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000010445 lecithin Nutrition 0.000 description 3
- 239000000787 lecithin Substances 0.000 description 3
- 229940067606 lecithin Drugs 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000004530 micro-emulsion Substances 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 230000003040 nociceptive effect Effects 0.000 description 3
- 239000000346 nonvolatile oil Substances 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- GJFYMYJYPARISZ-UHFFFAOYSA-N 1-bromo-2,5-difluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(F)=C(Br)C=C1F GJFYMYJYPARISZ-UHFFFAOYSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- JBKQHCAUZJBAND-UHFFFAOYSA-N 2-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]propan-2-ol Chemical compound C1=NC(C(C)(O)C)=NC=C1B1OC(C)(C)C(C)(C)O1 JBKQHCAUZJBAND-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QDNDBBUGYUSVSP-UHFFFAOYSA-N 3,6,10-triazatricyclo[6.3.0.02,6]undeca-1(11),2,4,7,9-pentaene Chemical compound N1=C2N(C=C1)C=C1C2=CN=C1 QDNDBBUGYUSVSP-UHFFFAOYSA-N 0.000 description 2
- MUTRMAZBGJEPMK-UHFFFAOYSA-N 3-(5-bromo-4-fluoro-2-nitrophenyl)-4-(2-hydroxyphenyl)-3-azabicyclo[3.1.0]hexan-2-one Chemical compound BrC=1C(=CC(=C(C=1)N1C(C2CC2C1C1=C(C=CC=C1)O)=O)[N+](=O)[O-])F MUTRMAZBGJEPMK-UHFFFAOYSA-N 0.000 description 2
- IIOKDOJKJGCOEP-UHFFFAOYSA-N 3h-pyrrolo[1,2-a]imidazole Chemical compound C1=CN2CC=NC2=C1 IIOKDOJKJGCOEP-UHFFFAOYSA-N 0.000 description 2
- 125000001963 4 membered heterocyclic group Chemical group 0.000 description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 2
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 108010029697 CD40 Ligand Proteins 0.000 description 2
- 102100032937 CD40 ligand Human genes 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000003807 Graves Disease Diseases 0.000 description 2
- 208000015023 Graves' disease Diseases 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 208000036576 Obstructive uropathy Diseases 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010038934 Retinopathy proliferative Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 101710187830 Tumor necrosis factor receptor superfamily member 1B Proteins 0.000 description 2
- 102100033733 Tumor necrosis factor receptor superfamily member 1B Human genes 0.000 description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
- 235000019437 butane-1,3-diol Nutrition 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000011111 cardboard Substances 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 229940097362 cyclodextrins Drugs 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 238000005888 cyclopropanation reaction Methods 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 125000002636 imidazolinyl group Chemical group 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- XFANWRJXACPLCS-UHFFFAOYSA-N methyl 2-[4-(5-bromopyrimidin-2-yl)piperazin-1-yl]acetate Chemical compound C1CN(CC(=O)OC)CCN1C1=NC=C(Br)C=N1 XFANWRJXACPLCS-UHFFFAOYSA-N 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000000651 prodrug Substances 0.000 description 2
- 229940002612 prodrug Drugs 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 201000002327 urinary tract obstruction Diseases 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- MUTRMAZBGJEPMK-KCWFYHRYSA-N (1S,4S,5R)-3-(5-bromo-4-fluoro-2-nitrophenyl)-4-(2-hydroxyphenyl)-3-azabicyclo[3.1.0]hexan-2-one Chemical compound BrC=1C(=CC(=C(C=1)N1C([C@H]2C[C@H]2[C@H]1C1=C(C=CC=C1)O)=O)[N+](=O)[O-])F MUTRMAZBGJEPMK-KCWFYHRYSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- BJEMFFWEUUXDTP-LSYCYVAJSA-N (3R,4R,6S)-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-LSYCYVAJSA-N 0.000 description 1
- GJAORLBTYRDLMO-JWQBTQOVSA-N (4R,6S)-12-bromo-11-fluoro-3-(2-phenoxyphenyl)-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(13),7,9,11-tetraene Chemical compound BrC1=CC2=C(N=C3N2C([C@H]2[C@@H]3C2)C2=C(C=CC=C2)OC2=CC=CC=C2)C=C1F GJAORLBTYRDLMO-JWQBTQOVSA-N 0.000 description 1
- NACQRCDPSHHQPT-BKSPAHHJSA-N (4aR,11R,11aS)-8-(6-methoxypyridin-3-yl)-11-phenyl-4,4a,11,11a-tetrahydro-1H-isoindolo[2,1-a]benzimidazole Chemical compound COc1ccc(cn1)-c1ccc2nc3[C@@H]4CC=CC[C@@H]4[C@H](c4ccccc4)n3c2c1 NACQRCDPSHHQPT-BKSPAHHJSA-N 0.000 description 1
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- QRADKVYIJIAENZ-UHFFFAOYSA-N 1-[[bromo(difluoro)methyl]-ethoxyphosphoryl]oxyethane Chemical compound CCOP(=O)(C(F)(F)Br)OCC QRADKVYIJIAENZ-UHFFFAOYSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- DVQWNQBEUKXONL-UHFFFAOYSA-N 1-iodo-2-methoxybenzene Chemical compound COC1=CC=CC=C1I DVQWNQBEUKXONL-UHFFFAOYSA-N 0.000 description 1
- JATVCSVVGDGTCL-UHFFFAOYSA-N 12-bromo-11-fluoro-3-(2-phenylmethoxyphenyl)-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(13),7,9,11-tetraene Chemical compound C(C1=CC=CC=C1)OC1=C(C=CC=C1)C1C2C(C=3N1C1=C(N=3)C=C(C(=C1)Br)F)C2 JATVCSVVGDGTCL-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- UNZALKVOBVBVPY-UHFFFAOYSA-N 2-(12-bromo-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(13),7,9,11-tetraen-3-yl)phenol Chemical compound BrC1=CC2=C(N=C3N2C(C2C3C2)C2=C(C=CC=C2)O)C=C1F UNZALKVOBVBVPY-UHFFFAOYSA-N 0.000 description 1
- QPBNHDFPMRENBC-UHFFFAOYSA-N 2-(difluoromethoxy)benzaldehyde Chemical compound FC(F)OC1=CC=CC=C1C=O QPBNHDFPMRENBC-UHFFFAOYSA-N 0.000 description 1
- UNZALKVOBVBVPY-KXTRXUQASA-N 2-[(4R,6S)-12-bromo-11-fluoro-2,8-diazatetracyclo[7.4.0.02,7.04,6]trideca-1(13),7,9,11-tetraen-3-yl]phenol Chemical compound BrC1=CC2=C(N=C3N2C([C@H]2[C@@H]3C2)C2=C(C=CC=C2)O)C=C1F UNZALKVOBVBVPY-KXTRXUQASA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 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 description 1
- DSEWTWHQTAWRCR-GCKMJXCFSA-N 2-[5-[(3S,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-GCKMJXCFSA-N 0.000 description 1
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- MGOLNIXAPIAKFM-UHFFFAOYSA-N 2-isocyanato-2-methylpropane Chemical compound CC(C)(C)N=C=O MGOLNIXAPIAKFM-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- CESUXLKAADQNTB-SSDOTTSWSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@](N)=O CESUXLKAADQNTB-SSDOTTSWSA-N 0.000 description 1
- 125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
- 125000001627 3 membered heterocyclic group Chemical group 0.000 description 1
- QMXQLXLVJKLLFG-UHFFFAOYSA-N 3-(5-bromo-4-fluoro-2-nitrophenyl)-4-(2-methoxyphenyl)-3-azabicyclo[3.1.0]hexan-2-one Chemical compound BrC=1C(=CC(=C(C=1)N1C(C2CC2C1C1=C(C=CC=C1)OC)=O)[N+](=O)[O-])F QMXQLXLVJKLLFG-UHFFFAOYSA-N 0.000 description 1
- NDNOQWFTUXKQOT-UHFFFAOYSA-N 3-(5-bromo-4-fluoro-2-nitrophenyl)-4-[2-(difluoromethoxy)phenyl]-3-azabicyclo[3.1.0]hexan-2-one Chemical compound BrC=1C(=CC(=C(C=1)N1C(C2CC2C1C1=C(C=CC=C1)OC(F)F)=O)[N+](=O)[O-])F NDNOQWFTUXKQOT-UHFFFAOYSA-N 0.000 description 1
- UHQOPDGATRGDDD-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexane-2,4-dione Chemical compound O=C1NC(=O)C2CC12 UHQOPDGATRGDDD-UHFFFAOYSA-N 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000001845 4 membered carbocyclic group Chemical group 0.000 description 1
- RGDHEEISNDCHFJ-UHFFFAOYSA-N 4-(2-methoxyphenyl)-3-azabicyclo[3.1.0]hexan-2-one Chemical compound COC1=C(C=CC=C1)C1NC(C2CC12)=O RGDHEEISNDCHFJ-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- HNVAYPJNFUXYII-UHFFFAOYSA-N 4-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]morpholine Chemical compound O1C(C)(C)C(C)(C)OB1C1=CN=C(N2CCOCC2)N=C1 HNVAYPJNFUXYII-UHFFFAOYSA-N 0.000 description 1
- YHWLBBPOKRHVAR-UHFFFAOYSA-N 5-bromo-2-piperazin-1-ylpyrimidine Chemical compound N1=CC(Br)=CN=C1N1CCNCC1 YHWLBBPOKRHVAR-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
- 208000026872 Addison Disease Diseases 0.000 description 1
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000030760 Anaemia of chronic disease Diseases 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 241000937413 Axia Species 0.000 description 1
- 229910015845 BBr3 Inorganic materials 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
- 108010017384 Blood Proteins Proteins 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
- 208000020084 Bone disease Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 1
- 0 C*(C)Cc(cc1)ccc1Oc1c([C@@]2[n]3c(cc(c(F)c4)Br)c4nc3[C@@]3[C@]2C3)cccc1 Chemical compound C*(C)Cc(cc1)ccc1Oc1c([C@@]2[n]3c(cc(c(F)c4)Br)c4nc3[C@@]3[C@]2C3)cccc1 0.000 description 1
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 description 1
- NZKHZULRTRNBAB-QULANZEGSA-N C[C@@H]([C@H]12)[C@@H]1c1nc(cc(c(Br)c3)F)c3[n]1[C@H]2c(cccc1)c1Oc1ccccc1 Chemical compound C[C@@H]([C@H]12)[C@@H]1c1nc(cc(c(Br)c3)F)c3[n]1[C@H]2c(cccc1)c1Oc1ccccc1 NZKHZULRTRNBAB-QULANZEGSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- 208000006029 Cardiomegaly Diseases 0.000 description 1
- 206010062746 Carditis Diseases 0.000 description 1
- 206010008685 Chondritis Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 238000006117 Diels-Alder cycloaddition reaction Methods 0.000 description 1
- 206010013801 Duchenne Muscular Dystrophy Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 208000027754 Endocrine autoimmune disease Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 206010018374 Glomerulonephritis minimal lesion Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical group Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- 208000004883 Lipoid Nephrosis Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- 206010025415 Macular oedema Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 208000029725 Metabolic bone disease Diseases 0.000 description 1
- 102000005741 Metalloproteases Human genes 0.000 description 1
- 108010006035 Metalloproteases Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- QUUPVBOIUYQRLI-WIEQDCTASA-N NC(c(nc1)ccc1-c(c(F)c1)cc2c1nc([C@@H]1[C@H]3C1)[n]2[C@H]3c(cccc1)c1OC(F)F)=O Chemical compound NC(c(nc1)ccc1-c(c(F)c1)cc2c1nc([C@@H]1[C@H]3C1)[n]2[C@H]3c(cccc1)c1OC(F)F)=O QUUPVBOIUYQRLI-WIEQDCTASA-N 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- 206010029260 Neuroblastoma Diseases 0.000 description 1
- 206010049088 Osteopenia Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 208000031845 Pernicious anaemia Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010035742 Pneumonitis Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000002389 Pouchitis Diseases 0.000 description 1
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 201000009594 Systemic Scleroderma Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 1
- 108091005956 Type II transmembrane proteins Proteins 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- 238000010958 [3+2] cycloaddition reaction Methods 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 150000001336 alkenes Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000007854 aminals Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 208000022400 anemia due to chronic disease Diseases 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 125000003725 azepanyl group Chemical group 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- OGBUMNBNEWYMNJ-UHFFFAOYSA-N batilol Chemical class CCCCCCCCCCCCCCCCCCOCC(O)CO OGBUMNBNEWYMNJ-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 1
- 125000005621 boronate group Chemical class 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 1
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 1
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
- 229960003115 certolizumab pegol Drugs 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000024207 chronic leukemia Diseases 0.000 description 1
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000012045 crude solution Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
- 125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 201000011190 diabetic macular edema Diseases 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- ZOCHARZZJNPSEU-UHFFFAOYSA-N diboron Chemical compound B#B ZOCHARZZJNPSEU-UHFFFAOYSA-N 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 125000004611 dihydroisoindolyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000008387 emulsifying waxe Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 208000010749 gastric carcinoma Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 229960001743 golimumab Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 150000002374 hemiaminals Chemical class 0.000 description 1
- 208000007475 hemolytic anemia Diseases 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- UBHWBODXJBSFLH-UHFFFAOYSA-N hexadecan-1-ol;octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCO UBHWBODXJBSFLH-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000005934 immune activation Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 208000027138 indeterminate colitis Diseases 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 208000021646 inflammation of heart layer Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 150000002505 iron Chemical class 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- TYQCGQRIZGCHNB-JLAZNSOCSA-N l-ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(O)=C(O)C1=O TYQCGQRIZGCHNB-JLAZNSOCSA-N 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- DBTNVRCCIDISMV-UHFFFAOYSA-L lithium;magnesium;propane;dichloride Chemical compound [Li+].[Mg+2].[Cl-].[Cl-].C[CH-]C DBTNVRCCIDISMV-UHFFFAOYSA-L 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 201000010230 macular retinal edema Diseases 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000001055 magnesium Nutrition 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- 235000012245 magnesium oxide Nutrition 0.000 description 1
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 206010027191 meningioma Diseases 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- FZXFNYFVNKTQSX-UHFFFAOYSA-J octanoate;rhodium(2+) Chemical compound [Rh+2].[Rh+2].CCCCCCCC([O-])=O.CCCCCCCC([O-])=O.CCCCCCCC([O-])=O.CCCCCCCC([O-])=O FZXFNYFVNKTQSX-UHFFFAOYSA-J 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N p-hydroxybenzoic acid propyl ester Natural products CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229950008679 protamine sulfate Drugs 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000004644 retinal vein occlusion Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 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
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 201000000498 stomach carcinoma Diseases 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 208000020408 systemic-onset juvenile idiopathic arthritis Diseases 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
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 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
- 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
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229960001295 tocopherol Drugs 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
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 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
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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]
-
- 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
-
- 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
Landscapes
- 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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562200415P | 2015-08-03 | 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 |
|---|---|
| ES2828696T3 true ES2828696T3 (es) | 2021-05-27 |
Family
ID=56610045
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16748045T Active ES2828696T3 (es) | 2015-08-03 | 2016-08-02 | Compuestos cíclicos útiles como moduladores de TNF alfa |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US10335392B2 (https=) |
| EP (1) | EP3331889B1 (https=) |
| JP (1) | JP6811233B2 (https=) |
| KR (1) | KR102679517B1 (https=) |
| CN (1) | CN108137609B (https=) |
| AU (1) | AU2016301215A1 (https=) |
| BR (1) | BR112018001980A2 (https=) |
| CA (1) | CA2994703A1 (https=) |
| EA (1) | EA201890421A1 (https=) |
| ES (1) | ES2828696T3 (https=) |
| IL (1) | IL257159A (https=) |
| MX (1) | MX2018001173A (https=) |
| WO (1) | WO2017023902A1 (https=) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3288939A1 (en) | 2015-04-17 | 2018-03-07 | AbbVie Inc. | Tricyclic modulators of tnf signaling |
| WO2016168633A1 (en) | 2015-04-17 | 2016-10-20 | Abbvie Inc. | Indazolones as modulators of tnf signaling |
| US9879016B2 (en) | 2015-04-17 | 2018-01-30 | 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 |
| GB201621907D0 (en) | 2016-12-21 | 2017-02-01 | Ucb Biopharma Sprl And Sanofi | Antibody epitope |
| KR102698413B1 (ko) | 2020-05-05 | 2024-08-26 | 뉴베일런트, 아이엔씨. | 헤테로방향족 거대환식 에터 화학치료제 |
| IL297832A (en) | 2020-05-05 | 2023-01-01 | Nuvalent Inc | Macrocyclic heteroaromatic chemotherapeutic agents |
| IL311444A (en) | 2021-10-01 | 2024-05-01 | Nuvalent Inc | Solid forms, pharmaceutical compositions and preparation of heteroaromatic macrocyclic ether compounds |
| EP4556478A4 (en) * | 2022-08-08 | 2025-10-22 | Medinno Pharmaceutical Tech Zhuhai Co Ltd | TGF-BETA INHIBITOR COMPOUND AND USE THEREOF |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5149386A (ja) * | 1974-10-28 | 1976-04-28 | Hitachi Ltd | Shuchukanshiseigyohoho |
| CA2281927C (en) | 1997-02-25 | 2004-01-27 | Christopher J. Michejda | 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 |
| 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 |
| 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 |
| CN103739605B (zh) | 2009-03-23 | 2016-08-17 | 伊莱利利公司 | 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 |
| 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 |
| 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 |
| GB201321735D0 (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 |
| GB201321746D0 (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 |
| GB201321738D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| US9920052B2 (en) | 2013-12-09 | 2018-03-20 | Ucb Biopharma Sprl | Imidazopyridine derivatives as modulators of TNF activity |
| GB201321744D0 (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 |
| GB201321739D0 (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 |
| GB201321728D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| RU2685234C1 (ru) | 2013-12-09 | 2019-04-17 | Юсб Байофарма Спрл | Конденсированные бициклические гетероароматические производные в качестве модуляторов активности tnf |
| GB201321745D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| MX388321B (es) | 2014-10-06 | 2025-03-19 | Signal Pharm Llc | Compuestos de aminopurina sustituida, composiciones del mismo, y metodos de tratamiento con los mismos. |
| ES2797685T3 (es) | 2015-03-18 | 2020-12-03 | Bristol Myers Squibb Co | Compuestos heterocíclicos tricíclicos útiles como inhibidores de TNF |
| CN107635993B (zh) | 2015-03-18 | 2020-05-22 | 百时美施贵宝公司 | 取代的三环杂环化合物 |
| WO2016149439A1 (en) | 2015-03-18 | 2016-09-22 | Bristol-Myers Squibb Company | Heterocyclic compounds useful as inhibitors of tnf |
-
2016
- 2016-08-02 BR BR112018001980A patent/BR112018001980A2/pt not_active Application Discontinuation
- 2016-08-02 KR KR1020187005708A patent/KR102679517B1/ko active Active
- 2016-08-02 CN CN201680057965.1A patent/CN108137609B/zh active Active
- 2016-08-02 EP EP16748045.8A patent/EP3331889B1/en active Active
- 2016-08-02 EA EA201890421A patent/EA201890421A1/ru unknown
- 2016-08-02 JP JP2018506125A patent/JP6811233B2/ja active Active
- 2016-08-02 CA CA2994703A patent/CA2994703A1/en not_active Abandoned
- 2016-08-02 US US15/749,611 patent/US10335392B2/en active Active
- 2016-08-02 AU AU2016301215A patent/AU2016301215A1/en not_active Abandoned
- 2016-08-02 MX MX2018001173A patent/MX2018001173A/es unknown
- 2016-08-02 WO PCT/US2016/045104 patent/WO2017023902A1/en not_active Ceased
- 2016-08-02 ES ES16748045T patent/ES2828696T3/es active Active
-
2018
- 2018-01-25 IL IL257159A patent/IL257159A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP3331889A1 (en) | 2018-06-13 |
| JP6811233B2 (ja) | 2021-01-13 |
| BR112018001980A2 (pt) | 2018-09-18 |
| IL257159A (en) | 2018-03-29 |
| US10335392B2 (en) | 2019-07-02 |
| WO2017023902A1 (en) | 2017-02-09 |
| KR20180031773A (ko) | 2018-03-28 |
| US20180221344A1 (en) | 2018-08-09 |
| KR102679517B1 (ko) | 2024-06-27 |
| MX2018001173A (es) | 2018-04-24 |
| CN108137609A (zh) | 2018-06-08 |
| CA2994703A1 (en) | 2017-02-09 |
| EP3331889B1 (en) | 2020-09-23 |
| EA201890421A1 (ru) | 2018-07-31 |
| JP2018525377A (ja) | 2018-09-06 |
| CN108137609B (zh) | 2021-07-16 |
| AU2016301215A1 (en) | 2018-03-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2828696T3 (es) | Compuestos cíclicos útiles como moduladores de TNF alfa | |
| KR102806565B1 (ko) | PD-L1 면역조절제로서의 테트라하이드로-이미다조[4,5-c]피리딘 유도체 | |
| ES2921020T3 (es) | Compuestos de indol sustituidos con [1,2,4]triazolo[4,3-a]piridinilo | |
| ES2956555T3 (es) | Proceso para la preparación de derivados de imidazol pentacíclicos condensados y usos de los mismos como moduladores de la actividad de TNF | |
| ES2803650T3 (es) | Compuestos heterocíclicos útiles como inhibidores de TNF | |
| BR112021009880A2 (pt) | pirimidina e derivado de heterociclo de nitrogênio de cinco membros, método de preparação para os mesmos e usos médicos dos mesmos | |
| ES2797685T3 (es) | Compuestos heterocíclicos tricíclicos útiles como inhibidores de TNF | |
| EP4194457A1 (en) | Compound for targeting and degrading protein, and preparation method therefor and use thereof | |
| ES2797805T3 (es) | Compuestos heterocíclicos tricíclicos sustituidos | |
| ES2840848T3 (es) | Derivados de piridilo como inhibidores de bromodominio | |
| ES3057371T3 (en) | Antagonists of the muscarinic acetylcholine receptor m4 | |
| ES2358445T3 (es) | Derivados de azabiciclo (3.1.0) hexano útiles como moduladores de los receptores d3 de dopamina. | |
| ES2963696T3 (es) | Compuestos diméricos de indol sustituidos | |
| ES2960521T3 (es) | Compuestos de pirazolo[3,4-D]pirrolo[1,2-B]piridazinilo útiles como inhibidores de IRAK4 | |
| ES3036306T3 (en) | Thienopyridinyl and thiazolopyridinyl compounds useful as irak4 inhibitors | |
| HK40098390A (en) | Heterocyclic compounds as immunomodulators | |
| HK40098390B (en) | Heterocyclic compounds as immunomodulators | |
| HK40049005B (en) | Tetrahydro-imidazo[4,5-c]pyridine derivatives as pd-l1 immunomodulators | |
| HK40049005A (en) | Tetrahydro-imidazo[4,5-c]pyridine derivatives as pd-l1 immunomodulators |