CA3154488A1 - Thyroid hormone receptor beta agonist compounds - Google Patents
Thyroid hormone receptor beta agonist compounds Download PDFInfo
- Publication number
- CA3154488A1 CA3154488A1 CA3154488A CA3154488A CA3154488A1 CA 3154488 A1 CA3154488 A1 CA 3154488A1 CA 3154488 A CA3154488 A CA 3154488A CA 3154488 A CA3154488 A CA 3154488A CA 3154488 A1 CA3154488 A1 CA 3154488A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- pharmaceutically acceptable
- acceptable salt
- mixture
- tautomer
- 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.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 315
- 229940123876 Thyroid hormone receptor beta agonist Drugs 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 61
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 102100033451 Thyroid hormone receptor beta Human genes 0.000 claims abstract description 6
- 108091008762 thyroid hormone receptors ß Proteins 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims description 121
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 63
- 125000005842 heteroatom Chemical group 0.000 claims description 43
- 125000000623 heterocyclic group Chemical group 0.000 claims description 42
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims description 27
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 21
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 7
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 530
- 239000000556 agonist Substances 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 630
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 374
- 229910001868 water Inorganic materials 0.000 description 360
- 238000003786 synthesis reaction Methods 0.000 description 262
- 230000015572 biosynthetic process Effects 0.000 description 261
- 239000000243 solution Substances 0.000 description 192
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 158
- 239000007832 Na2SO4 Substances 0.000 description 147
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 147
- 229910052938 sodium sulfate Inorganic materials 0.000 description 147
- 235000011152 sodium sulphate Nutrition 0.000 description 147
- 230000002829 reductive effect Effects 0.000 description 142
- 239000011541 reaction mixture Substances 0.000 description 132
- 239000012267 brine Substances 0.000 description 131
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 131
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 114
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 108
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 107
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 106
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 102
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 93
- 239000012044 organic layer Substances 0.000 description 84
- 239000003208 petroleum Substances 0.000 description 80
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 76
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 70
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 68
- 239000012074 organic phase Substances 0.000 description 66
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 65
- 101150041968 CDC13 gene Proteins 0.000 description 64
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 64
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 62
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 61
- 238000005481 NMR spectroscopy Methods 0.000 description 56
- 238000006243 chemical reaction Methods 0.000 description 56
- 239000012071 phase Substances 0.000 description 55
- 238000002953 preparative HPLC Methods 0.000 description 55
- 238000005160 1H NMR spectroscopy Methods 0.000 description 48
- 229910000027 potassium carbonate Inorganic materials 0.000 description 47
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 46
- 235000015320 potassium carbonate Nutrition 0.000 description 46
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 45
- 239000012299 nitrogen atmosphere Substances 0.000 description 39
- 239000000725 suspension Substances 0.000 description 39
- 229910004373 HOAc Inorganic materials 0.000 description 38
- 239000000706 filtrate Substances 0.000 description 37
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 35
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 32
- 235000010288 sodium nitrite Nutrition 0.000 description 32
- 201000010099 disease Diseases 0.000 description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 31
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 29
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 29
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 29
- 238000004440 column chromatography Methods 0.000 description 29
- 125000005638 hydrazono group Chemical group 0.000 description 29
- VMAATSFMXSMKPG-UHFFFAOYSA-N 1,3-dichloro-2-fluoro-5-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(Cl)=C(F)C(Cl)=C1 VMAATSFMXSMKPG-UHFFFAOYSA-N 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 28
- 125000000217 alkyl group Chemical group 0.000 description 28
- HDYZPOFPZYDBSF-UHFFFAOYSA-N 5-oxo-4H-1,2,4-oxadiazole-3-carbonyl chloride Chemical compound O=C1NC(=NO1)C(=O)Cl HDYZPOFPZYDBSF-UHFFFAOYSA-N 0.000 description 27
- 238000011282 treatment Methods 0.000 description 26
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 25
- HSOGVWWWGVFXGF-UHFFFAOYSA-N ethyl n-(2-cyanoacetyl)carbamate Chemical compound CCOC(=O)NC(=O)CC#N HSOGVWWWGVFXGF-UHFFFAOYSA-N 0.000 description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 24
- 208000035475 disorder Diseases 0.000 description 23
- 239000008346 aqueous phase Substances 0.000 description 22
- 229910052681 coesite Inorganic materials 0.000 description 21
- 229910052906 cristobalite Inorganic materials 0.000 description 21
- 239000000377 silicon dioxide Substances 0.000 description 21
- 235000012239 silicon dioxide Nutrition 0.000 description 21
- 239000007858 starting material Substances 0.000 description 21
- 229910052682 stishovite Inorganic materials 0.000 description 21
- 229910052905 tridymite Inorganic materials 0.000 description 21
- -1 ammonium cations Chemical class 0.000 description 18
- 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
- 239000012065 filter cake Substances 0.000 description 17
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- 239000012535 impurity Substances 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 239000003814 drug Substances 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 11
- 239000003643 water by type Substances 0.000 description 11
- VQCWSOYHHXXWSP-UHFFFAOYSA-N 4-bromo-2-fluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1F VQCWSOYHHXXWSP-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 9
- 150000001721 carbon Chemical group 0.000 description 9
- 238000011161 development Methods 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 235000019253 formic acid Nutrition 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- SKOWZLGOFVSKLB-UHFFFAOYSA-N hypodiboric acid Chemical compound OB(O)B(O)O SKOWZLGOFVSKLB-UHFFFAOYSA-N 0.000 description 9
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 208000032928 Dyslipidaemia Diseases 0.000 description 8
- 208000017170 Lipid metabolism disease Diseases 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000012453 solvate Substances 0.000 description 8
- 208000035150 Hypercholesterolemia Diseases 0.000 description 7
- 208000001145 Metabolic Syndrome Diseases 0.000 description 7
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 7
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 7
- 208000006575 hypertriglyceridemia Diseases 0.000 description 7
- OWPZYOFPXATQIS-UHFFFAOYSA-N 4-bromo-2-n-cyclopropylbenzene-1,2-diamine Chemical compound NC1=CC=C(Br)C=C1NC1CC1 OWPZYOFPXATQIS-UHFFFAOYSA-N 0.000 description 6
- WQNHSCZQLLEPOM-UHFFFAOYSA-N 4-bromo-2-n-methylbenzene-1,2-diamine Chemical compound CNC1=CC(Br)=CC=C1N WQNHSCZQLLEPOM-UHFFFAOYSA-N 0.000 description 6
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 6
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 6
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 6
- PADKBULQTHBQAM-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=C2C(=CC=NC2=CC=1)C)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=C2C(=CC=NC2=CC=1)C)Cl PADKBULQTHBQAM-UHFFFAOYSA-N 0.000 description 6
- 150000001204 N-oxides Chemical class 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000001099 ammonium carbonate Substances 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 230000009286 beneficial effect Effects 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 125000005843 halogen group Chemical group 0.000 description 6
- 238000010189 synthetic method Methods 0.000 description 6
- AIMREYQYBFBEGQ-UHFFFAOYSA-N 2-methyl-2-nitropropane Chemical compound CC(C)(C)[N+]([O-])=O AIMREYQYBFBEGQ-UHFFFAOYSA-N 0.000 description 5
- OPVFITKTWYWSQA-UHFFFAOYSA-N 4-bromo-2-N-(1-methylcyclopropyl)benzene-1,2-diamine Chemical compound CC1(CC1)Nc1cc(Br)ccc1N OPVFITKTWYWSQA-UHFFFAOYSA-N 0.000 description 5
- BJTHOBUPLBOIEM-UHFFFAOYSA-N 4-bromo-2-N-[1-(difluoromethyl)cyclopropyl]benzene-1,2-diamine Chemical compound BrC1=CC=C(C(=C1)NC1(CC1)C(F)F)N BJTHOBUPLBOIEM-UHFFFAOYSA-N 0.000 description 5
- OXYJCZYMCDLXRM-UHFFFAOYSA-N 4-bromo-2-n-propan-2-ylbenzene-1,2-diamine Chemical compound CC(C)NC1=CC(Br)=CC=C1N OXYJCZYMCDLXRM-UHFFFAOYSA-N 0.000 description 5
- XJZIXRNBUGMBOI-UHFFFAOYSA-N 4-bromo-2-n-tert-butylbenzene-1,2-diamine Chemical compound CC(C)(C)NC1=CC(Br)=CC=C1N XJZIXRNBUGMBOI-UHFFFAOYSA-N 0.000 description 5
- HATMKVQSHAMVPK-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=C2C(=CC=NC2=CC=1)CC)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=C2C(=CC=NC2=CC=1)CC)Cl HATMKVQSHAMVPK-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 230000008484 agonism Effects 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 235000012501 ammonium carbonate Nutrition 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- AHJWSRRHTXRLAQ-UHFFFAOYSA-N tetramethoxymethane Chemical compound COC(OC)(OC)OC AHJWSRRHTXRLAQ-UHFFFAOYSA-N 0.000 description 5
- 125000000335 thiazolyl group Chemical group 0.000 description 5
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 5
- FCTFTOZZSBMZRM-UHFFFAOYSA-N (3-methylquinolin-6-yl)boronic acid Chemical compound CC=1C=NC2=CC=C(C=C2C=1)B(O)O FCTFTOZZSBMZRM-UHFFFAOYSA-N 0.000 description 4
- APOYTRAZFJURPB-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)-n-(trifluoro-$l^{4}-sulfanyl)ethanamine Chemical compound COCCN(S(F)(F)F)CCOC APOYTRAZFJURPB-UHFFFAOYSA-N 0.000 description 4
- IQSHXDVWCIRILF-UHFFFAOYSA-N 6-(2,6-dichloro-4-nitrophenoxy)-4-ethylquinoline Chemical compound ClC1=C(OC=2C=C3C(=CC=NC3=CC=2)CC)C(=CC(=C1)[N+](=O)[O-])Cl IQSHXDVWCIRILF-UHFFFAOYSA-N 0.000 description 4
- 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 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- 238000010256 biochemical assay Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- FXYXDDGFTYTHAE-VUTHCHCSSA-N ethyl N-[(2E)-2-cyano-2-[[3,5-dichloro-4-(4-methylquinolin-6-yl)oxyphenyl]hydrazinylidene]acetyl]carbamate Chemical compound C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=C2C(=CC=NC2=CC=1)C)Cl FXYXDDGFTYTHAE-VUTHCHCSSA-N 0.000 description 4
- 235000003599 food sweetener Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000002541 furyl group Chemical group 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 125000003386 piperidinyl group Chemical group 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 125000000168 pyrrolyl group Chemical group 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 125000003107 substituted aryl group Chemical group 0.000 description 4
- 239000003765 sweetening agent Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 4
- 235000019798 tripotassium phosphate Nutrition 0.000 description 4
- LGSFWZLGCZBLSS-UHFFFAOYSA-N 1-(5-bromo-2-nitroanilino)cyclopropane-1-carbaldehyde Chemical compound BrC=1C=CC(=C(C=1)NC1(CC1)C=O)[N+](=O)[O-] LGSFWZLGCZBLSS-UHFFFAOYSA-N 0.000 description 3
- FBWOFVFUKXZXKT-UHFFFAOYSA-N 1-(trifluoromethyl)cyclopropan-1-amine Chemical compound FC(F)(F)C1(N)CC1 FBWOFVFUKXZXKT-UHFFFAOYSA-N 0.000 description 3
- NZQVOEZBRSXQRC-UHFFFAOYSA-N 2-(4-amino-2,6-dichlorophenoxy)-N-methyl-5-nitropyridin-4-amine Chemical compound NC1=CC(=C(OC2=NC=C(C(=C2)NC)[N+](=O)[O-])C(=C1)Cl)Cl NZQVOEZBRSXQRC-UHFFFAOYSA-N 0.000 description 3
- ANHDIJYKEZNILQ-UHFFFAOYSA-N 2-[[5-(2,6-dichloro-4-nitrophenoxy)-3-methoxyindazol-1-yl]methoxy]ethyl-trimethylsilane Chemical compound ClC1=C(OC=2C=C3C(=NN(C3=CC=2)COCC[Si](C)(C)C)OC)C(=CC(=C1)[N+](=O)[O-])Cl ANHDIJYKEZNILQ-UHFFFAOYSA-N 0.000 description 3
- VBYZWJMZASVGNB-UHFFFAOYSA-N 2-amino-5-bromobenzaldehyde Chemical compound NC1=CC=C(Br)C=C1C=O VBYZWJMZASVGNB-UHFFFAOYSA-N 0.000 description 3
- RVNSQGRBRZBBLJ-UHFFFAOYSA-N 2-chloro-n-methyl-5-nitropyridin-4-amine Chemical compound CNC1=CC(Cl)=NC=C1[N+]([O-])=O RVNSQGRBRZBBLJ-UHFFFAOYSA-N 0.000 description 3
- NZOUAUZAHAWSOK-UHFFFAOYSA-N 3-(2-amino-5-bromoanilino)propan-1-ol Chemical compound NC1=CC=C(Br)C=C1NCCCO NZOUAUZAHAWSOK-UHFFFAOYSA-N 0.000 description 3
- FQYJDQFHSGORSJ-UHFFFAOYSA-N 3-(5-bromo-2-nitroanilino)propan-1-ol Chemical compound OCCCNC1=CC(Br)=CC=C1[N+]([O-])=O FQYJDQFHSGORSJ-UHFFFAOYSA-N 0.000 description 3
- LPSCFCRUNJXWME-UHFFFAOYSA-N 3-methylbenzimidazol-5-ol Chemical compound C1=C(O)C=C2N(C)C=NC2=C1 LPSCFCRUNJXWME-UHFFFAOYSA-N 0.000 description 3
- MEWQFVUDMDGJLA-UHFFFAOYSA-N 3-methylquinolin-6-ol Chemical compound C1=CC(O)=CC2=CC(C)=CN=C21 MEWQFVUDMDGJLA-UHFFFAOYSA-N 0.000 description 3
- DHIZLNPSALVZBY-UHFFFAOYSA-N 4-bromo-2-n-ethylbenzene-1,2-diamine Chemical compound CCNC1=CC(Br)=CC=C1N DHIZLNPSALVZBY-UHFFFAOYSA-N 0.000 description 3
- QXNPFPJBKLAQJG-UHFFFAOYSA-N 4-chloroquinolin-6-ol Chemical compound N1=CC=C(Cl)C2=CC(O)=CC=C21 QXNPFPJBKLAQJG-UHFFFAOYSA-N 0.000 description 3
- KJMOZKCVLGUQRO-UHFFFAOYSA-N 4-ethyl-6-methoxyquinoline Chemical compound C1=C(OC)C=C2C(CC)=CC=NC2=C1 KJMOZKCVLGUQRO-UHFFFAOYSA-N 0.000 description 3
- DRLCPOBTLVIBBE-UHFFFAOYSA-N 4-ethylquinolin-6-ol Chemical compound C1=C(O)C=C2C(CC)=CC=NC2=C1 DRLCPOBTLVIBBE-UHFFFAOYSA-N 0.000 description 3
- DRHIPRPVOHVRCC-UHFFFAOYSA-N 4-methoxy-2-N-[1-(trifluoromethyl)cyclopropyl]benzene-1,2-diamine Chemical compound COc1ccc(N)c(NC2(CC2)C(F)(F)F)c1 DRHIPRPVOHVRCC-UHFFFAOYSA-N 0.000 description 3
- ULRBCMBSTWUHPK-UHFFFAOYSA-N 5-bromo-3-ethyl-2h-indazole Chemical compound C1=CC(Br)=CC2=C(CC)NN=C21 ULRBCMBSTWUHPK-UHFFFAOYSA-N 0.000 description 3
- XDJNHYAQZWCIAH-UHFFFAOYSA-N 5-bromo-3-methyl-2h-indazole Chemical compound C1=CC(Br)=CC2=C(C)NN=C21 XDJNHYAQZWCIAH-UHFFFAOYSA-N 0.000 description 3
- FXOQUYKHAQDUDT-UHFFFAOYSA-N 5-bromo-n-tert-butyl-2-nitroaniline Chemical compound CC(C)(C)NC1=CC(Br)=CC=C1[N+]([O-])=O FXOQUYKHAQDUDT-UHFFFAOYSA-N 0.000 description 3
- MELCKPFGESJODY-UHFFFAOYSA-N 5-methoxy-2-nitro-N-[1-(trifluoromethyl)cyclopropyl]aniline Chemical compound COc1ccc(c(NC2(CC2)C(F)(F)F)c1)[N+]([O-])=O MELCKPFGESJODY-UHFFFAOYSA-N 0.000 description 3
- AHTJBOZUJWOYFB-UHFFFAOYSA-N 6-(2,6-dichloro-4-nitrophenoxy)quinoline Chemical compound ClC1=C(OC=2C=C3C=CC=NC3=CC=2)C(=CC(=C1)[N+](=O)[O-])Cl AHTJBOZUJWOYFB-UHFFFAOYSA-N 0.000 description 3
- VNTFEWXYAOATFA-UHFFFAOYSA-N 6-bromo-2h-1,2,4-triazine-3,5-dione Chemical compound BrC1=NNC(=O)NC1=O VNTFEWXYAOATFA-UHFFFAOYSA-N 0.000 description 3
- VLKIHAKQTRBPLC-UHFFFAOYSA-N 6-bromo-3-methylquinoline Chemical compound C1=CC(Br)=CC2=CC(C)=CN=C21 VLKIHAKQTRBPLC-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 108010011485 Aspartame Proteins 0.000 description 3
- ADAKLJXMMIKCOW-TWKHWXDSSA-N C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=C2C(=CC=NC2=CC=1)CC)Cl Chemical compound C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=C2C(=CC=NC2=CC=1)CC)Cl ADAKLJXMMIKCOW-TWKHWXDSSA-N 0.000 description 3
- BEBMWLCVLYHDAH-VUTHCHCSSA-N C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=C2C=CC(=NC2=CC=1)C)Cl Chemical compound C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=C2C=CC(=NC2=CC=1)C)Cl BEBMWLCVLYHDAH-VUTHCHCSSA-N 0.000 description 3
- LZCSIQAHXUKNKR-UHFFFAOYSA-N C(C)(C)N1C(=NC2=C1C=C(C=C2)O)OC Chemical compound C(C)(C)N1C(=NC2=C1C=C(C=C2)O)OC LZCSIQAHXUKNKR-UHFFFAOYSA-N 0.000 description 3
- PONKFBFDCKSDCW-UHFFFAOYSA-N C1(CC1)C1=CC=NC2=CC=C(C=C12)O Chemical compound C1(CC1)C1=CC=NC2=CC=C(C=C12)O PONKFBFDCKSDCW-UHFFFAOYSA-N 0.000 description 3
- OPFAKTYKGDQTGC-UHFFFAOYSA-N ClC1=C(OC=2C=C3C(=CC=NC3=CC=2)C)C(=CC(=C1)[N+](=O)[O-])Cl Chemical compound ClC1=C(OC=2C=C3C(=CC=NC3=CC=2)C)C(=CC(=C1)[N+](=O)[O-])Cl OPFAKTYKGDQTGC-UHFFFAOYSA-N 0.000 description 3
- MUKCXSLZLGEDCR-UHFFFAOYSA-N ClC1=C(OC=2C=C3C=C(C=NC3=CC=2)C)C(=CC(=C1)[N+](=O)[O-])Cl Chemical compound ClC1=C(OC=2C=C3C=C(C=NC3=CC=2)C)C(=CC(=C1)[N+](=O)[O-])Cl MUKCXSLZLGEDCR-UHFFFAOYSA-N 0.000 description 3
- NBAUYHSHHLFGAH-UHFFFAOYSA-N ClC1=C(OC=2C=C3C=CC(=NC3=CC=2)C)C(=CC(=C1)[N+](=O)[O-])Cl Chemical compound ClC1=C(OC=2C=C3C=CC(=NC3=CC=2)C)C(=CC(=C1)[N+](=O)[O-])Cl NBAUYHSHHLFGAH-UHFFFAOYSA-N 0.000 description 3
- HZFJAKRBXNQZME-UHFFFAOYSA-N ClC1=NC2=CC=C(C=C2C=C1)OC1=C(C=C(C=C1Cl)[N+](=O)[O-])Cl Chemical compound ClC1=NC2=CC=C(C=C2C=C1)OC1=C(C=C(C=C1Cl)[N+](=O)[O-])Cl HZFJAKRBXNQZME-UHFFFAOYSA-N 0.000 description 3
- ZAADHACXMQXJJG-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=C2C(=CC=NC2=CC=1)C1CC1)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=C2C(=CC=NC2=CC=1)C1CC1)Cl ZAADHACXMQXJJG-UHFFFAOYSA-N 0.000 description 3
- OTZSJQDDYPLVIT-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=C2C=C(C=NC2=CC=1)C)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=C2C=C(C=NC2=CC=1)C)Cl OTZSJQDDYPLVIT-UHFFFAOYSA-N 0.000 description 3
- PWVIWUBBXCQFNW-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=C2C=CC(=NC2=CC=1)C)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=C2C=CC(=NC2=CC=1)C)Cl PWVIWUBBXCQFNW-UHFFFAOYSA-N 0.000 description 3
- UOZCTOMEDBCSRH-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=C2C=CC=NC2=CC=1)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=C2C=CC=NC2=CC=1)Cl UOZCTOMEDBCSRH-UHFFFAOYSA-N 0.000 description 3
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 3
- 229930091371 Fructose Natural products 0.000 description 3
- 239000005715 Fructose Substances 0.000 description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 3
- 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 3
- 108010081348 HRT1 protein Hairy Proteins 0.000 description 3
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 3
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 3
- 206010020850 Hyperthyroidism Diseases 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
- 239000005913 Maltodextrin Substances 0.000 description 3
- 229920002774 Maltodextrin Polymers 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 3
- CVSSJADLCPLYOA-UHFFFAOYSA-N NC1=CC(=C(OC2=CC(=C(C=N2)N)NC)C(=C1)Cl)Cl Chemical compound NC1=CC(=C(OC2=CC(=C(C=N2)N)NC)C(=C1)Cl)Cl CVSSJADLCPLYOA-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- FDGKMLWEXDCFQK-UHFFFAOYSA-N [1-(5-bromo-2-nitroanilino)cyclopropyl]methanol Chemical compound OCC1(CC1)Nc1cc(Br)ccc1[N+]([O-])=O FDGKMLWEXDCFQK-UHFFFAOYSA-N 0.000 description 3
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 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 3
- 239000000605 aspartame Substances 0.000 description 3
- 235000010357 aspartame Nutrition 0.000 description 3
- 229960003438 aspartame Drugs 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 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 3
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 125000003636 chemical group Chemical group 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- NDWFDXCDWJYUBP-NJZRLIGZSA-N ethyl N-[(2E)-2-cyano-2-[[3,5-dichloro-4-(4-cyclopropylquinolin-6-yl)oxyphenyl]hydrazinylidene]acetyl]carbamate Chemical compound C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=C2C(=CC=NC2=CC=1)C1CC1)Cl NDWFDXCDWJYUBP-NJZRLIGZSA-N 0.000 description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
- 150000002460 imidazoles Chemical class 0.000 description 3
- 125000002883 imidazolyl group Chemical group 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 229940035034 maltodextrin Drugs 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000002757 morpholinyl group Chemical group 0.000 description 3
- 238000004806 packaging method and process Methods 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 229910052717 sulfur Chemical group 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- GHEKGGDYVHWSBM-UHFFFAOYSA-N tert-butyl n-[1-(trifluoromethyl)cyclopropyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1(C(F)(F)F)CC1 GHEKGGDYVHWSBM-UHFFFAOYSA-N 0.000 description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 3
- PDAZFJXUXOGOLH-UHFFFAOYSA-N 1-(1-methylcyclopropyl)benzimidazol-5-ol Chemical compound CC1(CC1)N1C=NC2=C1C=CC(=C2)O PDAZFJXUXOGOLH-UHFFFAOYSA-N 0.000 description 2
- FLMPEVUFMTVQQZ-UHFFFAOYSA-N 2-[(5-bromo-3-methoxyindazol-1-yl)methoxy]ethyl-trimethylsilane Chemical compound BrC=1C=C2C(=NN(C2=CC=1)COCC[Si](C)(C)C)OC FLMPEVUFMTVQQZ-UHFFFAOYSA-N 0.000 description 2
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 2
- WORIZMDSXJNMLZ-UHFFFAOYSA-N 2-methylindazol-5-ol Chemical compound C1=C(O)C=CC2=NN(C)C=C21 WORIZMDSXJNMLZ-UHFFFAOYSA-N 0.000 description 2
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 2
- YWLITZBEAMRCEC-UHFFFAOYSA-N 3-ethylbenzimidazol-5-ol Chemical compound C1=C(O)C=C2N(CC)C=NC2=C1 YWLITZBEAMRCEC-UHFFFAOYSA-N 0.000 description 2
- ZEYXLIKGXIXLGC-UHFFFAOYSA-N 3-methoxy-1-(2-trimethylsilylethoxymethyl)indazol-5-ol Chemical compound COC1=NN(C2=CC=C(C=C12)O)COCC[Si](C)(C)C ZEYXLIKGXIXLGC-UHFFFAOYSA-N 0.000 description 2
- CIKAMJMJYBKKMS-UHFFFAOYSA-N 3-propan-2-ylbenzimidazol-5-ol Chemical compound C1=C(O)C=C2N(C(C)C)C=NC2=C1 CIKAMJMJYBKKMS-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- BEOVBLPXVFICSP-UHFFFAOYSA-N 4-chloro-6-methoxyquinoline Chemical compound N1=CC=C(Cl)C2=CC(OC)=CC=C21 BEOVBLPXVFICSP-UHFFFAOYSA-N 0.000 description 2
- 125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 2
- FTVGSRGPTYFWRQ-UHFFFAOYSA-N 5-bromo-n-methyl-2-nitroaniline Chemical compound CNC1=CC(Br)=CC=C1[N+]([O-])=O FTVGSRGPTYFWRQ-UHFFFAOYSA-N 0.000 description 2
- KQGDCQRXRDQKGN-UHFFFAOYSA-N 5-hydroxy-3-methyl-1-(2-trimethylsilylethoxymethyl)benzimidazol-2-one Chemical compound OC1=CC2=C(N(C(N2C)=O)COCC[Si](C)(C)C)C=C1 KQGDCQRXRDQKGN-UHFFFAOYSA-N 0.000 description 2
- VVPNCBKJQCDXTP-UHFFFAOYSA-N 6-(2,6-dichloro-4-nitrophenoxy)-1-(1-methylcyclopropyl)benzimidazole Chemical compound ClC1=C(OC=2C=CC3=C(N(C=N3)C3(CC3)C)C=2)C(=CC(=C1)[N+](=O)[O-])Cl VVPNCBKJQCDXTP-UHFFFAOYSA-N 0.000 description 2
- NGEBEBRIZCRBKT-UHFFFAOYSA-N 6-bromo-1-ethylbenzimidazole Chemical compound C1=C(Br)C=C2N(CC)C=NC2=C1 NGEBEBRIZCRBKT-UHFFFAOYSA-N 0.000 description 2
- ZMBCEUCYOIVNFM-UHFFFAOYSA-N 6-bromo-1-propan-2-ylbenzimidazole Chemical compound C1=C(Br)C=C2N(C(C)C)C=NC2=C1 ZMBCEUCYOIVNFM-UHFFFAOYSA-N 0.000 description 2
- ADGQWBHWMLHCJB-UHFFFAOYSA-N 6-bromo-1-tert-butyl-2-methoxybenzimidazole Chemical compound BrC=1C=CC2=C(N(C(=N2)OC)C(C)(C)C)C=1 ADGQWBHWMLHCJB-UHFFFAOYSA-N 0.000 description 2
- RMPQGDULPICHJK-UHFFFAOYSA-N 6-bromo-1-tert-butylbenzimidazole Chemical compound C1=C(Br)C=C2N(C(C)(C)C)C=NC2=C1 RMPQGDULPICHJK-UHFFFAOYSA-N 0.000 description 2
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- KKZVCYZCTZPGSX-UHFFFAOYSA-N BrC1=CC2=C(N=C3OCCCN32)C=C1 Chemical compound BrC1=CC2=C(N=C3OCCCN32)C=C1 KKZVCYZCTZPGSX-UHFFFAOYSA-N 0.000 description 2
- VWHCSRNBRWPWSX-UHFFFAOYSA-N BrC=1C=CC2=C(N(C=N2)C2(CC2)C)C=1 Chemical compound BrC=1C=CC2=C(N(C=N2)C2(CC2)C)C=1 VWHCSRNBRWPWSX-UHFFFAOYSA-N 0.000 description 2
- COTMFAVPMKNLTP-UXHLAJHPSA-N C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=CC2=C(N(C=N2)C2(CC2)C)C=1)Cl Chemical compound C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=CC2=C(N(C=N2)C2(CC2)C)C=1)Cl COTMFAVPMKNLTP-UXHLAJHPSA-N 0.000 description 2
- REVFRPFVPGHQFY-UHFFFAOYSA-N C(C)(C)(C)N1C(=NC2=C1C=C(C=C2)O)OC Chemical compound C(C)(C)(C)N1C(=NC2=C1C=C(C=C2)O)OC REVFRPFVPGHQFY-UHFFFAOYSA-N 0.000 description 2
- SHYZJBQYCMCMSZ-UHFFFAOYSA-N C(C)(C)(C)N1C=NC2=C1C=C(C=C2)O Chemical compound C(C)(C)(C)N1C=NC2=C1C=C(C=C2)O SHYZJBQYCMCMSZ-UHFFFAOYSA-N 0.000 description 2
- QQSILKXUKZZYRX-UHFFFAOYSA-N C(C)(C)(C)N1C=NC2=C1C=C(C=C2)OC1=C(C=C(C=C1Cl)[N+](=O)[O-])Cl Chemical compound C(C)(C)(C)N1C=NC2=C1C=C(C=C2)OC1=C(C=C(C=C1Cl)[N+](=O)[O-])Cl QQSILKXUKZZYRX-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- KIEHNFNOSVSCPP-UHFFFAOYSA-N ClC1=C(OC2=CC3=C(N=C4OCCCN43)C=C2)C(=CC(=C1)[N+](=O)[O-])Cl Chemical compound ClC1=C(OC2=CC3=C(N=C4OCCCN43)C=C2)C(=CC(=C1)[N+](=O)[O-])Cl KIEHNFNOSVSCPP-UHFFFAOYSA-N 0.000 description 2
- ZTDFBGWGQZEDPC-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC1=CC2=C(N=C3OCCCN32)C=C1)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC1=CC2=C(N=C3OCCCN32)C=C1)Cl ZTDFBGWGQZEDPC-UHFFFAOYSA-N 0.000 description 2
- VONOWGOGNDXEAF-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=CC2=C(N(C(=N2)OC)C2CC2)C=1)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=CC2=C(N(C(=N2)OC)C2CC2)C=1)Cl VONOWGOGNDXEAF-UHFFFAOYSA-N 0.000 description 2
- ADMFKQRGCKTVQX-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=CC2=C(N(C=N2)C)C=1)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=CC2=C(N(C=N2)C)C=1)Cl ADMFKQRGCKTVQX-UHFFFAOYSA-N 0.000 description 2
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 2
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 229920002148 Gellan gum Polymers 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000238367 Mya arenaria Species 0.000 description 2
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 2
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 229930006000 Sucrose Natural products 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
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 2
- ZEROXCFXWFDYLO-UHFFFAOYSA-N [3-methyl-2-oxo-1-(2-trimethylsilylethoxymethyl)benzimidazol-5-yl]boronic acid Chemical compound CN1C(N(C2=C1C=C(C=C2)B(O)O)COCC[Si](C)(C)C)=O ZEROXCFXWFDYLO-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 239000000908 ammonium hydroxide Substances 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000003725 azepanyl group Chemical group 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 239000006274 endogenous ligand Substances 0.000 description 2
- LDUPQHBPSGYBAZ-MTDXEUNCSA-N ethyl N-[(2E)-2-cyano-2-[(3,5-dichloro-4-quinolin-6-yloxyphenyl)hydrazinylidene]acetyl]carbamate Chemical compound C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=C2C=CC=NC2=CC=1)Cl LDUPQHBPSGYBAZ-MTDXEUNCSA-N 0.000 description 2
- OZBJPZIKZGMDHB-STBIYBPSSA-N ethyl N-[(2E)-2-cyano-2-[[3,5-dichloro-4-(3,4-dihydro-2H-[1,3]oxazino[3,2-a]benzimidazol-7-yloxy)phenyl]hydrazinylidene]acetyl]carbamate Chemical compound C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC1=CC2=C(N=C3OCCCN32)C=C1)Cl OZBJPZIKZGMDHB-STBIYBPSSA-N 0.000 description 2
- ULJVXIDNMZLTDL-VUTHCHCSSA-N ethyl N-[(2E)-2-cyano-2-[[3,5-dichloro-4-(3-methylquinolin-6-yl)oxyphenyl]hydrazinylidene]acetyl]carbamate Chemical compound C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=C2C=C(C=NC2=CC=1)C)Cl ULJVXIDNMZLTDL-VUTHCHCSSA-N 0.000 description 2
- 235000010492 gellan gum Nutrition 0.000 description 2
- 239000000216 gellan gum Substances 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 208000003532 hypothyroidism Diseases 0.000 description 2
- 230000002989 hypothyroidism Effects 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 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
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 150000002829 nitrogen Chemical class 0.000 description 2
- 108091008686 nuclear receptors type II Proteins 0.000 description 2
- 102000027507 nuclear receptors type II Human genes 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 125000003373 pyrazinyl group Chemical group 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 238000004808 supercritical fluid chromatography Methods 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 125000003831 tetrazolyl group Chemical group 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- 239000005495 thyroid hormone Substances 0.000 description 2
- 229940036555 thyroid hormone Drugs 0.000 description 2
- 238000002877 time resolved fluorescence resonance energy transfer Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 125000004306 triazinyl group Chemical group 0.000 description 2
- 125000001425 triazolyl group Chemical group 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- OBMKZINZPBARIK-UHFFFAOYSA-N (1-aminocyclopropyl)methanol Chemical compound OCC1(N)CC1 OBMKZINZPBARIK-UHFFFAOYSA-N 0.000 description 1
- UKSZBOKPHAQOMP-SVLSSHOZSA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 UKSZBOKPHAQOMP-SVLSSHOZSA-N 0.000 description 1
- GDCWZYRWKSOYGQ-UHFFFAOYSA-N (2-amino-5-bromophenyl)methanol Chemical compound NC1=CC=C(Br)C=C1CO GDCWZYRWKSOYGQ-UHFFFAOYSA-N 0.000 description 1
- HPJGEESDHAUUQR-SKGSPYGFSA-N (2s)-2-[[(2s)-5-(diaminomethylideneamino)-2-[[(2s)-1-[(2s)-5-(diaminomethylideneamino)-2-[[(2s)-2-[[(2s)-3-naphthalen-2-yl-2-(3-pyridin-3-ylpropanoylamino)propanoyl]amino]-3-phenylpropanoyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]amino]buta Chemical compound NC(=O)C[C@@H](C(N)=O)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=C2C=CC=CC2=CC=1)NC(=O)CCC=1C=NC=CC=1)CC1=CC=CC=C1 HPJGEESDHAUUQR-SKGSPYGFSA-N 0.000 description 1
- FOLCUFKJHSQMEL-BIXPGCQOSA-N (4-butylcyclohexyl) N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-3-[(3S)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]pentan-2-yl]carbamate Chemical compound CCCCC1CCC(CC1)OC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C[C@@H]2CCNC2=O)C=O FOLCUFKJHSQMEL-BIXPGCQOSA-N 0.000 description 1
- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 1
- 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 1
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- ZTNPZJQLIBWJDY-UHFFFAOYSA-N 1-(5-bromo-2-fluorophenyl)propan-1-one Chemical compound CCC(=O)C1=CC(Br)=CC=C1F ZTNPZJQLIBWJDY-UHFFFAOYSA-N 0.000 description 1
- SKCBKBCACWDALV-UHFFFAOYSA-N 1-(trifluoromethyl)cyclopropane-1-carboxylic acid Chemical compound OC(=O)C1(C(F)(F)F)CC1 SKCBKBCACWDALV-UHFFFAOYSA-N 0.000 description 1
- VSRXAWSAKJABKW-UHFFFAOYSA-N 1-methylcyclopropan-1-amine Chemical compound CC1(N)CC1 VSRXAWSAKJABKW-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- RZVJQUMDJUUBBF-UHFFFAOYSA-N 2,4-dichloro-5-nitropyridine Chemical compound [O-][N+](=O)C1=CN=C(Cl)C=C1Cl RZVJQUMDJUUBBF-UHFFFAOYSA-N 0.000 description 1
- KVKNRVFJKKKJBO-UHFFFAOYSA-N 2-(7-bromo-5-methyl-1h-indol-3-yl)ethanamine Chemical compound CC1=CC(Br)=C2NC=C(CCN)C2=C1 KVKNRVFJKKKJBO-UHFFFAOYSA-N 0.000 description 1
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 1
- XANCOYIVTNZKOE-UHFFFAOYSA-N 2-chloroquinolin-6-ol Chemical compound N1=C(Cl)C=CC2=CC(O)=CC=C21 XANCOYIVTNZKOE-UHFFFAOYSA-N 0.000 description 1
- NLTAHTYBZZSCIT-UHFFFAOYSA-N 2-iodo-4-methoxy-1-nitrobenzene Chemical compound COC1=CC=C([N+]([O-])=O)C(I)=C1 NLTAHTYBZZSCIT-UHFFFAOYSA-N 0.000 description 1
- USSQQASIZNTRAJ-UHFFFAOYSA-N 2-methylquinolin-6-ol Chemical compound C1=C(O)C=CC2=NC(C)=CC=C21 USSQQASIZNTRAJ-UHFFFAOYSA-N 0.000 description 1
- GOXTXMUCJOIIOK-UHFFFAOYSA-N 3,4-dihydro-2H-[1,3]oxazino[3,2-a]benzimidazol-7-ol Chemical compound O1C=2N(CCC1)C1=C(N=2)C=CC(=C1)O GOXTXMUCJOIIOK-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
- ASNHGEVAWNWCRQ-UHFFFAOYSA-N 4-(hydroxymethyl)oxolane-2,3,4-triol Chemical compound OCC1(O)COC(O)C1O ASNHGEVAWNWCRQ-UHFFFAOYSA-N 0.000 description 1
- KGEXISHTCZHGFT-UHFFFAOYSA-N 4-azaniumyl-2,6-dichlorophenolate Chemical compound NC1=CC(Cl)=C(O)C(Cl)=C1 KGEXISHTCZHGFT-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- YSCLQXFVKXKSMU-UHFFFAOYSA-N 4-methylquinolin-6-ol Chemical compound C1=C(O)C=C2C(C)=CC=NC2=C1 YSCLQXFVKXKSMU-UHFFFAOYSA-N 0.000 description 1
- FASQPXTZYZCTMG-UHFFFAOYSA-N 5-bromo-2-nitro-n-propan-2-ylaniline Chemical compound CC(C)NC1=CC(Br)=CC=C1[N+]([O-])=O FASQPXTZYZCTMG-UHFFFAOYSA-N 0.000 description 1
- ABWHVHBGFZUYAA-UHFFFAOYSA-N 5-bromo-3-methoxy-1h-indazole Chemical compound C1=C(Br)C=C2C(OC)=NNC2=C1 ABWHVHBGFZUYAA-UHFFFAOYSA-N 0.000 description 1
- CLDFNRWDFOWGLC-UHFFFAOYSA-N 5-bromo-n-ethyl-2-nitroaniline Chemical compound CCNC1=CC(Br)=CC=C1[N+]([O-])=O CLDFNRWDFOWGLC-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 229910015845 BBr3 Inorganic materials 0.000 description 1
- 239000004135 Bone phosphate Substances 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- WNCJQFUUNZVAOD-UHFFFAOYSA-N ClC=1C=C(C=C(C=1OC=1C=C2C=CC=NC2=CC=1)Cl)N1N=C(C(NC1=O)=O)C#N Chemical compound ClC=1C=C(C=C(C=1OC=1C=C2C=CC=NC2=CC=1)Cl)N1N=C(C(NC1=O)=O)C#N WNCJQFUUNZVAOD-UHFFFAOYSA-N 0.000 description 1
- RCFCPGAMNISVFO-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=C2C(=NNC2=CC=1)C)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=C2C(=NNC2=CC=1)C)Cl RCFCPGAMNISVFO-UHFFFAOYSA-N 0.000 description 1
- OTGCLXMOTUDNGH-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=C2C=CC(=NC2=CC=1)C1CC1)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=C2C=CC(=NC2=CC=1)C1CC1)Cl OTGCLXMOTUDNGH-UHFFFAOYSA-N 0.000 description 1
- JDHZIZQMEDRFMV-UHFFFAOYSA-N ClC=1C=C(N)C=C(C=1OC=1C=CC2=C(N(C=N2)C2CC2)C=1)Cl Chemical compound ClC=1C=C(N)C=C(C=1OC=1C=CC2=C(N(C=N2)C2CC2)C=1)Cl JDHZIZQMEDRFMV-UHFFFAOYSA-N 0.000 description 1
- 229940126650 Compound 3f Drugs 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 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
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 1
- 102000020897 Formins Human genes 0.000 description 1
- 108091022623 Formins Proteins 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-O Imidazolium Chemical compound C1=C[NH+]=CN1 RAXXELZNTBOGNW-UHFFFAOYSA-O 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229910003202 NH4 Inorganic materials 0.000 description 1
- 101100042258 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) sem-1 gene Proteins 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 description 1
- 101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 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 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- 150000001556 benzimidazoles Chemical class 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229940125388 beta agonist Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- PFYXSUNOLOJMDX-UHFFFAOYSA-N bis(2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)ON1C(=O)CCC1=O PFYXSUNOLOJMDX-UHFFFAOYSA-N 0.000 description 1
- 230000008416 bone turnover Effects 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 150000001649 bromium compounds Chemical class 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
- 229910052792 caesium Inorganic materials 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000004623 carbolinyl group Chemical group 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical group C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 125000006165 cyclic alkyl 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
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 1
- WMKGGPCROCCUDY-PHEQNACWSA-N dibenzylideneacetone Chemical compound C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 WMKGGPCROCCUDY-PHEQNACWSA-N 0.000 description 1
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- WUOHCOHOUUTBLE-UHFFFAOYSA-N ditert-butyl(cyclopentyl)phosphane Chemical compound CC(C)(C)P(C(C)(C)C)C1CCCC1 WUOHCOHOUUTBLE-UHFFFAOYSA-N 0.000 description 1
- JQZFOBWXNREQLO-UHFFFAOYSA-L ditert-butyl(cyclopentyl)phosphane;dichloropalladium;iron Chemical compound [Fe].Cl[Pd]Cl.CC(C)(C)P(C(C)(C)C)[C]1[CH][CH][CH][CH]1.CC(C)(C)P(C(C)(C)C)[C]1[CH][CH][CH][CH]1 JQZFOBWXNREQLO-UHFFFAOYSA-L 0.000 description 1
- SACNIGZYDTUHKB-UHFFFAOYSA-N ditert-butyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C(C)(C)C)C(C)(C)C SACNIGZYDTUHKB-UHFFFAOYSA-N 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- XXCSRTQGNFDIQZ-NJZRLIGZSA-N ethyl N-[(2E)-2-cyano-2-[[3,5-dichloro-4-(2-cyclopropylquinolin-6-yl)oxyphenyl]hydrazinylidene]acetyl]carbamate Chemical compound C(#N)\C(\C(=O)NC(OCC)=O)=N/NC1=CC(=C(C(=C1)Cl)OC=1C=C2C=CC(=NC2=CC=1)C1CC1)Cl XXCSRTQGNFDIQZ-NJZRLIGZSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- UKAJDOBPPOAZSS-UHFFFAOYSA-N ethyl(trimethyl)silane Chemical compound CC[Si](C)(C)C UKAJDOBPPOAZSS-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000009459 flexible packaging Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical class C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000008040 ionic compounds Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 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
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 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
- 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
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 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
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000005545 phthalimidyl group Chemical group 0.000 description 1
- 239000010773 plant oil Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 125000005412 pyrazyl group Chemical group 0.000 description 1
- 125000005495 pyridazyl group Chemical group 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- OVYWMEWYEJLIER-UHFFFAOYSA-N quinolin-6-ol Chemical compound N1=CC=CC2=CC(O)=CC=C21 OVYWMEWYEJLIER-UHFFFAOYSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000012216 screening Methods 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
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962891078P | 2019-08-23 | 2019-08-23 | |
| US62/891,078 | 2019-08-23 | ||
| US202062967943P | 2020-01-30 | 2020-01-30 | |
| US62/967,943 | 2020-01-30 | ||
| PCT/US2020/047467 WO2021041237A1 (en) | 2019-08-23 | 2020-08-21 | Thyroid hormone receptor beta agonist compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3154488A1 true CA3154488A1 (en) | 2021-03-04 |
Family
ID=74684314
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3154488A Pending CA3154488A1 (en) | 2019-08-23 | 2020-08-21 | Thyroid hormone receptor beta agonist compounds |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20220281849A1 (enExample) |
| EP (1) | EP4017875A4 (enExample) |
| JP (2) | JP7646632B2 (enExample) |
| CN (1) | CN114430743A (enExample) |
| AU (1) | AU2020336272A1 (enExample) |
| CA (1) | CA3154488A1 (enExample) |
| WO (1) | WO2021041237A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN121081472A (zh) | 2018-12-13 | 2025-12-09 | 拓臻股份有限公司 | 一种THRβ受体激动剂化合物及其制备方法和用途 |
| SG11202111552YA (en) | 2019-05-08 | 2021-11-29 | Aligos Therapeutics Inc | MODULATORS OF THR-ß AND METHODS OF USE THEREOF |
| CN114375193B (zh) | 2019-09-12 | 2024-05-14 | 拓臻制药公司 | 甲状腺激素受体β激动剂化合物 |
| AU2021306314A1 (en) | 2020-07-10 | 2023-02-09 | Aligos Therapeutics, Inc. | Modulators of THR-β and methods of use thereof |
| WO2022037617A1 (zh) * | 2020-08-19 | 2022-02-24 | 成都凡诺西生物医药科技有限公司 | 腈代三嗪类衍生物及其制备方法和应用 |
| CN117120051A (zh) * | 2021-03-03 | 2023-11-24 | 拓臻制药公司 | 甲状腺激素受体β激动剂化合物 |
| JP7665774B2 (ja) * | 2021-03-19 | 2025-04-21 | メッドシャイン ディスカバリー インコーポレイテッド | 二環式フェノール系化合物及びその使用 |
| TW202313615A (zh) * | 2021-05-21 | 2023-04-01 | 大陸商深圳微芯生物科技股份有限公司 | 一種雜環化合物及其應用 |
| CN113979963B (zh) * | 2021-12-24 | 2022-03-11 | 凯思凯旭(上海)医药科技有限公司 | 一种作为甲状腺激素β受体激动剂的化合物及其用途 |
| CN116354934A (zh) * | 2021-12-28 | 2023-06-30 | 中国科学院上海药物研究所 | 一类喹啉类化合物及其制备方法、药物组合物和用途 |
| TW202506131A (zh) | 2023-04-07 | 2025-02-16 | 美商拓臻製藥公司 | ＧＬＰ－１Ｒ及ＴＨＲβ激動劑之組合以及其使用方法 |
| CN120923503A (zh) * | 2025-10-10 | 2025-11-11 | 吉斯凯(苏州)制药有限公司 | 具有杂环结构的化合物、THRβ受体激动剂及用途 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE297905T1 (de) * | 1999-09-30 | 2005-07-15 | Pfizer Prod Inc | 6-azauracilderivate als liganden der thyroidrezeptoren |
| US6787652B1 (en) * | 1999-09-30 | 2004-09-07 | Pfizer, Inc. | 6-Azauracil derivatives as thyroid receptor ligands |
| GB0015205D0 (en) * | 2000-06-21 | 2000-08-09 | Karobio Ab | Bioisosteric thyroid receptor ligands and method |
| GB0513692D0 (en) * | 2005-07-04 | 2005-08-10 | Karobio Ab | Novel pharmaceutical compositions |
| KR100965006B1 (ko) * | 2005-07-21 | 2010-06-21 | 에프. 호프만-라 로슈 아게 | 갑상선 호르몬 수용체 작용제로서 피리다진온 유도체 |
| GB0608724D0 (en) * | 2006-05-03 | 2006-06-14 | Karobio Ab | Novel Pharmaceutical Compositions |
| GB0610322D0 (en) * | 2006-05-24 | 2006-07-05 | Karobio Ab | Novel pharmaceutical compositions |
| US8076334B2 (en) * | 2007-09-20 | 2011-12-13 | Hoffmann-La Roche Inc. | Prodrugs of thyroid hormone analogs |
| CN102459185B (zh) * | 2009-04-20 | 2015-06-03 | 田边三菱制药株式会社 | 新型甲状腺激素β受体激动剂 |
| IL266054B2 (en) * | 2016-10-18 | 2023-10-01 | Madrigal Pharmaceuticals Inc | Methods for treating liver disorders or lipid disorders using a THR-BETA agonist |
| CN111646979B (zh) * | 2018-01-23 | 2021-08-31 | 深圳市塔吉瑞生物医药有限公司 | 取代的哒嗪酮化合物 |
| CN119552152A (zh) * | 2018-10-12 | 2025-03-04 | 益方生物科技(上海)股份有限公司 | 甲状腺激素受体激动剂 |
| EP3927693A4 (en) * | 2019-02-21 | 2023-04-05 | Nanjing Ruijie Pharma Co., Ltd. | NOVEL COMPOUNDS AND THEIR USES AS THYROID HORMONE RECEPTOR AGONISTS |
| SG11202111552YA (en) * | 2019-05-08 | 2021-11-29 | Aligos Therapeutics Inc | MODULATORS OF THR-ß AND METHODS OF USE THEREOF |
-
2020
- 2020-08-21 EP EP20856291.8A patent/EP4017875A4/en active Pending
- 2020-08-21 AU AU2020336272A patent/AU2020336272A1/en active Pending
- 2020-08-21 CN CN202080066442.XA patent/CN114430743A/zh active Pending
- 2020-08-21 WO PCT/US2020/047467 patent/WO2021041237A1/en not_active Ceased
- 2020-08-21 US US17/637,426 patent/US20220281849A1/en active Pending
- 2020-08-21 CA CA3154488A patent/CA3154488A1/en active Pending
- 2020-08-21 JP JP2022512349A patent/JP7646632B2/ja active Active
-
2025
- 2025-03-05 JP JP2025034294A patent/JP2025106242A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2025106242A (ja) | 2025-07-15 |
| AU2020336272A1 (en) | 2022-04-14 |
| US20220281849A1 (en) | 2022-09-08 |
| JP2022544714A (ja) | 2022-10-20 |
| EP4017875A4 (en) | 2023-05-03 |
| EP4017875A1 (en) | 2022-06-29 |
| CN114430743A (zh) | 2022-05-03 |
| WO2021041237A1 (en) | 2021-03-04 |
| JP7646632B2 (ja) | 2025-03-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7646632B2 (ja) | 甲状腺ホルモン受容体ベータアゴニスト化合物 | |
| JP7579253B2 (ja) | 甲状腺ホルモン受容体ベータアゴニスト化合物 | |
| JP2022110080A (ja) | Ｅｈｍｔ２阻害剤としてのアミン置換複素環化合物およびその使用方法 | |
| CA3168494A1 (en) | Pgdh inhibitors and methods of making and using | |
| US11203587B2 (en) | Thyroid hormone receptor beta agonist compounds | |
| JP7611832B2 (ja) | 特定の白血病を治療するための化合物 | |
| CA3212130A1 (en) | Thyroid hormone receptor beta agonist compounds | |
| US11312715B2 (en) | Fused ring derivative as A2A receptor inhibitor | |
| CA2948765A1 (en) | Intermediate (4-bromo-2-fluorophenyl)-1h-imidazoyl derivatives for use in a process to synthesize benzoxazepin compounds | |
| JP2019533650A (ja) | Ｅｈｍｔ２阻害剤としての置換された融合二環式または三環式複素環化合物 | |
| CA3178647A1 (en) | Substituted tricyclic amides, analogues thereof, and methods using same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20220929 |
|
| EEER | Examination request |
Effective date: 20220929 |
|
| EEER | Examination request |
Effective date: 20220929 |
|
| EEER | Examination request |
Effective date: 20220929 |
|
| EEER | Examination request |
Effective date: 20220929 |