ES2709195T3 - Compuesto tricíclico y uso del mismo - Google Patents
Compuesto tricíclico y uso del mismo Download PDFInfo
- Publication number
- ES2709195T3 ES2709195T3 ES14756272T ES14756272T ES2709195T3 ES 2709195 T3 ES2709195 T3 ES 2709195T3 ES 14756272 T ES14756272 T ES 14756272T ES 14756272 T ES14756272 T ES 14756272T ES 2709195 T3 ES2709195 T3 ES 2709195T3
- Authority
- ES
- Spain
- Prior art keywords
- acid
- methoxy
- methyl
- dihydro
- propoxy
- 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
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 929
- -1 methylsulfonylpropoxy, ethylsulfonylpropoxy, ethoxyethoxy, morpholino, morpholinoethoxy, tetrahydrofuranoyloxy Chemical group 0.000 claims abstract description 616
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 208
- 239000001257 hydrogen Substances 0.000 claims abstract description 49
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 18
- 239000012453 solvate Substances 0.000 claims abstract description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
- 125000001424 substituent group Chemical group 0.000 claims abstract description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims abstract description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Chemical group C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims abstract description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 3
- 125000001207 fluorophenyl group Chemical group 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims description 464
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 360
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 266
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 203
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 131
- 239000000203 mixture Substances 0.000 claims description 120
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 claims description 74
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 50
- 125000004323 oxepin-2-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C(*)O1 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 239000011734 sodium Substances 0.000 claims description 18
- 206010012601 diabetes mellitus Diseases 0.000 claims description 17
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 13
- 229910052708 sodium Inorganic materials 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 8
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 7
- 208000010444 Acidosis Diseases 0.000 claims description 5
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 5
- 208000036487 Arthropathies Diseases 0.000 claims description 5
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 5
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
- 206010022489 Insulin Resistance Diseases 0.000 claims description 5
- 208000012659 Joint disease Diseases 0.000 claims description 5
- 208000007976 Ketosis Diseases 0.000 claims description 5
- 208000001344 Macular Edema Diseases 0.000 claims description 5
- 206010025415 Macular oedema Diseases 0.000 claims description 5
- 208000029725 Metabolic bone disease Diseases 0.000 claims description 5
- 206010049088 Osteopenia Diseases 0.000 claims description 5
- 208000007536 Thrombosis Diseases 0.000 claims description 5
- 230000007950 acidosis Effects 0.000 claims description 5
- 208000026545 acidosis disease Diseases 0.000 claims description 5
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 5
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 5
- 208000035475 disorder Diseases 0.000 claims description 5
- 201000006549 dyspepsia Diseases 0.000 claims description 5
- 201000008980 hyperinsulinism Diseases 0.000 claims description 5
- 230000004140 ketosis Effects 0.000 claims description 5
- 201000010230 macular retinal edema Diseases 0.000 claims description 5
- 208000017443 reproductive system disease Diseases 0.000 claims description 5
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 4
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 4
- 206010013700 Drug hypersensitivity Diseases 0.000 claims description 4
- 206010060378 Hyperinsulinaemia Diseases 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 208000013016 Hypoglycemia Diseases 0.000 claims description 4
- 206010024604 Lipoatrophy Diseases 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 206010030113 Oedema Diseases 0.000 claims description 4
- 208000033626 Renal failure acute Diseases 0.000 claims description 4
- 201000011040 acute kidney failure Diseases 0.000 claims description 4
- 208000012998 acute renal failure Diseases 0.000 claims description 4
- 235000021229 appetite regulation Nutrition 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 206010016256 fatigue Diseases 0.000 claims description 4
- 230000003451 hyperinsulinaemic effect Effects 0.000 claims description 4
- 208000027866 inflammatory disease Diseases 0.000 claims description 4
- 206010022498 insulinoma Diseases 0.000 claims description 4
- 230000002503 metabolic effect Effects 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 208000021255 pancreatic insulinoma Diseases 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- HQIZDGAMCWYBKS-UHFFFAOYSA-M sodium;cyclopropanecarboxylate Chemical compound [Na+].[O-]C(=O)C1CC1 HQIZDGAMCWYBKS-UHFFFAOYSA-M 0.000 claims description 4
- PZTZGJQYSKESEO-XMMPIXPASA-N 2-[(3s)-6-[[9-[(1,1-dioxothian-4-yl)methoxy]-11-methyl-6,7-dihydrobenzo[d][1]benzoxepin-2-yl]methoxy]-2,3-dihydro-1-benzofuran-3-yl]acetic acid Chemical compound C=1C=2CCOC3=CC=C(COC=4C=C5OC[C@@H](CC(O)=O)C5=CC=4)C=C3C=2C(C)=CC=1OCC1CCS(=O)(=O)CC1 PZTZGJQYSKESEO-XMMPIXPASA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 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 claims description 3
- 125000004321 azepin-2-yl group Chemical group [H]N1C([H])=C([H])C([H])=C([H])C([H])=C1* 0.000 claims description 3
- 230000007812 deficiency Effects 0.000 claims description 3
- 239000011737 fluorine Chemical group 0.000 claims description 3
- 229910052731 fluorine Chemical group 0.000 claims description 3
- 239000008103 glucose Substances 0.000 claims description 3
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 3
- 208000026278 immune system disease Diseases 0.000 claims description 3
- 230000000512 lipotoxic effect Effects 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- 230000000007 visual effect Effects 0.000 claims description 3
- QOHKYKXTHSACMM-FTJBHMTQSA-N (1S,2S)-2-[4-[[9-(1,1-dioxothian-4-yl)oxy-11-methyl-6,7-dihydrobenzo[d][1]benzoxepin-2-yl]methylamino]-2-fluorophenyl]cyclopropane-1-carboxylic acid Chemical compound O=S1(CCC(CC1)OC1=CC2=C(C3=C(OCC2)C=CC(=C3)CNC3=CC(=C(C=C3)[C@@H]3[C@H](C3)C(=O)O)F)C(=C1)C)=O QOHKYKXTHSACMM-FTJBHMTQSA-N 0.000 claims description 2
- CGWPBESTZZSVNU-DEOSSOPVSA-N (3S)-3-[4-[[5-methyl-7-(3-methylsulfonylpropoxy)-9,10-dihydrophenanthren-1-yl]methoxy]phenyl]hex-4-ynoic acid Chemical compound CC1=C2C=3C=CC=C(C3CCC2=CC(=C1)OCCCS(=O)(=O)C)COC1=CC=C(C=C1)[C@H](CC(=O)O)C#CC CGWPBESTZZSVNU-DEOSSOPVSA-N 0.000 claims description 2
- BDAJKDNHONYIEE-SANMLTNESA-N (3S)-3-[4-[[5-methyl-7-(3-methylsulfonylpropoxy)-9,10-dihydrophenanthren-3-yl]methoxy]phenyl]hex-4-ynoic acid Chemical compound CC1=C2C=3C=C(C=CC3CCC2=CC(=C1)OCCCS(=O)(=O)C)COC1=CC=C(C=C1)[C@H](CC(=O)O)C#CC BDAJKDNHONYIEE-SANMLTNESA-N 0.000 claims description 2
- 125000000586 2-(4-morpholinyl)ethoxy group Chemical group [H]C([H])(O*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 2
- GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 claims description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 2
- VLCZMSUIFYTVHK-VPUSJEBWSA-N (1S,2S)-2-[4-[[9-(3-methylsulfonylpropoxy)-6,7-dihydrobenzo[d][1]benzoxepin-2-yl]methoxy]phenyl]cyclopropane-1-carboxylic acid Chemical compound CS(=O)(=O)CCCOC1=CC2=C(C3=C(OCC2)C=CC(=C3)COC3=CC=C(C=C3)[C@@H]3[C@H](C3)C(=O)O)C=C1 VLCZMSUIFYTVHK-VPUSJEBWSA-N 0.000 claims 1
- FTNHPSKGTRCBES-RPBOFIJWSA-N (1s,2s)-2-[4-[[10-methyl-8-(3-methylsulfonylpropoxy)-6h-benzo[c]chromen-2-yl]methoxy]phenyl]cyclopropane-1-carboxylic acid Chemical compound C1=C2C=3C(C)=CC(OCCCS(C)(=O)=O)=CC=3COC2=CC=C1COC(C=C1)=CC=C1[C@H]1C[C@@H]1C(O)=O FTNHPSKGTRCBES-RPBOFIJWSA-N 0.000 claims 1
- IXSCGBODJGIJNN-UHFFFAOYSA-N 2-(4-fluorophenyl)propanoic acid Chemical compound OC(=O)C(C)C1=CC=C(F)C=C1 IXSCGBODJGIJNN-UHFFFAOYSA-N 0.000 claims 1
- 230000006735 deficit Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000013403 hyperactivity Diseases 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 10
- 125000006519 CCH3 Chemical group 0.000 abstract 1
- 125000001153 fluoro group Chemical group F* 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 description 523
- 238000005481 NMR spectroscopy Methods 0.000 description 419
- 238000000034 method Methods 0.000 description 333
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 210
- 239000006260 foam Substances 0.000 description 185
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 144
- 239000007787 solid Substances 0.000 description 112
- 239000011541 reaction mixture Substances 0.000 description 99
- 239000012230 colorless oil Substances 0.000 description 94
- 230000002829 reductive effect Effects 0.000 description 94
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 92
- 239000012044 organic layer Substances 0.000 description 76
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 72
- 235000019439 ethyl acetate Nutrition 0.000 description 68
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 64
- 239000000243 solution Substances 0.000 description 64
- 238000010898 silica gel chromatography Methods 0.000 description 63
- 238000004587 chromatography analysis Methods 0.000 description 54
- 239000000741 silica gel Substances 0.000 description 54
- 229910002027 silica gel Inorganic materials 0.000 description 54
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- 239000003921 oil Substances 0.000 description 49
- 235000019198 oils Nutrition 0.000 description 49
- 239000007864 aqueous solution Substances 0.000 description 45
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- 229920006395 saturated elastomer Polymers 0.000 description 40
- 229910052938 sodium sulfate Inorganic materials 0.000 description 39
- 235000011152 sodium sulphate Nutrition 0.000 description 39
- 239000000706 filtrate Substances 0.000 description 37
- 229910000027 potassium carbonate Inorganic materials 0.000 description 36
- 235000015320 potassium carbonate Nutrition 0.000 description 35
- YMGUBTXCNDTFJI-UHFFFAOYSA-M cyclopropanecarboxylate Chemical compound [O-]C(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-M 0.000 description 34
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 32
- 235000019341 magnesium sulphate Nutrition 0.000 description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
- 125000000217 alkyl group Chemical group 0.000 description 30
- 125000003545 alkoxy group Chemical group 0.000 description 26
- 239000012153 distilled water Substances 0.000 description 25
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 24
- 239000000460 chlorine Substances 0.000 description 23
- 125000000623 heterocyclic group Chemical group 0.000 description 23
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 19
- 125000004452 carbocyclyl group Chemical group 0.000 description 19
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 19
- 208000004998 Abdominal Pain Diseases 0.000 description 18
- 208000002881 Colic Diseases 0.000 description 18
- 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 18
- 229910052736 halogen Inorganic materials 0.000 description 17
- 150000002367 halogens Chemical class 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 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 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 102100026148 Free fatty acid receptor 1 Human genes 0.000 description 15
- 101000912510 Homo sapiens Free fatty acid receptor 1 Proteins 0.000 description 15
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 150000004702 methyl esters Chemical class 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
- 125000002252 acyl group Chemical group 0.000 description 11
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 11
- 239000000543 intermediate Substances 0.000 description 11
- 229910052717 sulfur Inorganic materials 0.000 description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 10
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- 125000002947 alkylene group Chemical group 0.000 description 9
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 8
- 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 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 7
- 125000005997 bromomethyl group Chemical group 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 7
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 7
- 229910015845 BBr3 Inorganic materials 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
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- JOCYKKRVIIGZJH-UHFFFAOYSA-N methyl 4-amino-5-bromo-2-fluorobenzoate Chemical compound COC(C1=C(C=C(C(=C1)Br)N)F)=O JOCYKKRVIIGZJH-UHFFFAOYSA-N 0.000 description 1
- FEIOASZZURHTHB-UHFFFAOYSA-N methyl 4-formylbenzoate Chemical compound COC(=O)C1=CC=C(C=O)C=C1 FEIOASZZURHTHB-UHFFFAOYSA-N 0.000 description 1
- HAPIXNBOBZHNCA-UHFFFAOYSA-N methyl 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate Chemical compound COC(=O)C1=CC=C(C)C(B2OC(C)(C)C(C)(C)O2)=C1 HAPIXNBOBZHNCA-UHFFFAOYSA-N 0.000 description 1
- GXSQFUMROJXWQB-UHFFFAOYSA-N methyl 5-bromo-2-fluoro-4-[3-(3-methoxyphenyl)propyl]benzoate Chemical compound BrC=1C(=CC(=C(C(=O)OC)C=1)F)CCCC1=CC(=CC=C1)OC GXSQFUMROJXWQB-UHFFFAOYSA-N 0.000 description 1
- HALGDDHZSLHFSX-UHFFFAOYSA-N methyl 5-methyl-7-(3-methylsulfonylpropoxy)-9,10-dihydrophenanthrene-1-carboxylate Chemical compound CC1=C2C=3C=CC=C(C3CCC2=CC(=C1)OCCCS(=O)(=O)C)C(=O)OC HALGDDHZSLHFSX-UHFFFAOYSA-N 0.000 description 1
- IJWPOWUWTLABPI-UHFFFAOYSA-N methyl 5-methyl-7-(3-methylsulfonylpropoxy)-9,10-dihydrophenanthrene-3-carboxylate Chemical compound CC1=C2C=3C=C(C=CC3CCC2=CC(=C1)OCCCS(=O)(=O)C)C(=O)OC IJWPOWUWTLABPI-UHFFFAOYSA-N 0.000 description 1
- HLOVJLDTNASCAN-UHFFFAOYSA-N methyl 7-(2-ethoxyethoxy)-5-methyl-9,10-dihydrophenanthrene-3-carboxylate Chemical compound C(C)OCCOC1=CC(=C2C=3C=C(C=CC3CCC2=C1)C(=O)OC)C HLOVJLDTNASCAN-UHFFFAOYSA-N 0.000 description 1
- WXBNQEZSGCBMIG-UHFFFAOYSA-N methyl 7-hydroxy-5-methyl-9,10-dihydrophenanthrene-1-carboxylate Chemical compound OC1=CC(=C2C=3C=CC=C(C3CCC2=C1)C(=O)OC)C WXBNQEZSGCBMIG-UHFFFAOYSA-N 0.000 description 1
- BUNOZDLGCIJHQG-UHFFFAOYSA-N methyl 7-hydroxy-5-methyl-9,10-dihydrophenanthrene-3-carboxylate Chemical compound OC1=CC(=C2C=3C=C(C=CC3CCC2=C1)C(=O)OC)C BUNOZDLGCIJHQG-UHFFFAOYSA-N 0.000 description 1
- MRCIPCDKNQIIGL-UHFFFAOYSA-N methyl 7-methoxy-5-methyl-9,10-dihydrophenanthrene-1-carboxylate Chemical compound COC1=CC(=C2C=3C=CC=C(C3CCC2=C1)C(=O)OC)C MRCIPCDKNQIIGL-UHFFFAOYSA-N 0.000 description 1
- JRCBRNDSTPUFCX-UHFFFAOYSA-N methyl 7-methoxy-5-methyl-9,10-dihydrophenanthrene-3-carboxylate Chemical compound COC1=CC(=C2C=3C=C(C=CC3CCC2=C1)C(=O)OC)C JRCBRNDSTPUFCX-UHFFFAOYSA-N 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-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
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 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
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
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- 229940069265 ophthalmic ointment Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- PMDLIAGAGUCEGN-UHFFFAOYSA-N oxepine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC=CO1 PMDLIAGAGUCEGN-UHFFFAOYSA-N 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- SEVSMVUOKAMPDO-UHFFFAOYSA-N para-Acetoxybenzaldehyde Natural products CC(=O)OC1=CC=C(C=O)C=C1 SEVSMVUOKAMPDO-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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- 235000011181 potassium carbonates Nutrition 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-UHFFFAOYSA-N 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 125000003373 pyrazinyl 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
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 239000001476 sodium potassium tartrate Substances 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
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- 238000001308 synthesis method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- YODQQARABJQLIP-UHFFFAOYSA-N thian-4-ol Chemical compound OC1CCSCC1 YODQQARABJQLIP-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl 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
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
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- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
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- 235000013343 vitamin Nutrition 0.000 description 1
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Classifications
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- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
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- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D223/18—Dibenzazepines; Hydrogenated dibenzazepines
- C07D223/20—Dibenz [b, e] azepines; Hydrogenated dibenz [b, e] azepines
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
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- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
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- C07D313/02—Seven-membered rings
- C07D313/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D313/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
- C07D313/12—[b,e]-condensed
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- C07D335/02—Heterocyclic compounds containing six-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
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- 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
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- C—CHEMISTRY; METALLURGY
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- C07C2603/00—Systems containing at least three condensed rings
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- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
- C07C2603/26—Phenanthrenes; Hydrogenated phenanthrenes
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- C—CHEMISTRY; METALLURGY
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- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/30—Ortho- or ortho- and peri-condensed systems containing three rings containing seven-membered rings
- C07C2603/32—Dibenzocycloheptenes; Hydrogenated dibenzocycloheptenes
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| KR20130022038 | 2013-02-28 | ||
| KR20130109840 | 2013-09-12 | ||
| PCT/KR2014/001686 WO2014133361A1 (ko) | 2013-02-28 | 2014-02-28 | 삼환식 화합물 및 이의 용도 |
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| ES2709195T3 true ES2709195T3 (es) | 2019-04-15 |
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| WO2016105383A1 (en) * | 2014-12-23 | 2016-06-30 | Boral Ip Holdings (Australia) Pty Limited | Rapid setting material for improved processing and performance of carbonating metal silicate cement |
| MX2018007844A (es) | 2015-12-22 | 2019-01-21 | Jiangsu Hengrui Medicine Co | Derivado de benzopiperidina, metodo de preparacion del mismo y su uso medico del mismo. |
| KR102538719B1 (ko) | 2016-12-08 | 2023-06-01 | 메르크 파텐트 게엠베하 | 중합가능한 화합물 및 액정 디스플레이에서 이의 용도 |
| CN108218824B (zh) * | 2016-12-09 | 2020-06-26 | 中国科学院大连化学物理研究所 | 二苯基并[b,d]氧杂环庚烷化合物及其制备和应用 |
| CN110177773B (zh) | 2017-01-26 | 2023-08-25 | 勃林格殷格翰国际有限公司 | 苄基氨基吡啶基环丙烷羧酸、其药物组合物及其用途 |
| EP3573959B1 (en) | 2017-01-26 | 2021-07-28 | Boehringer Ingelheim International GmbH | Benzylaminopyrazinylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof |
| JP7050792B2 (ja) | 2017-01-26 | 2022-04-08 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ベンジルオキシピラジニルシクロプロパンカルボン酸、その医薬組成物及び使用 |
| US10913720B2 (en) | 2017-01-26 | 2021-02-09 | Boehringer Ingelheim International Gmbh | Benzyloxypyridylcyclopropanecarboxylic acids, pharmaceutical compositions and uses thereof |
| US10550127B1 (en) | 2017-02-08 | 2020-02-04 | Boehringer Ingelheim International Gmbh | Indanylaminoazadihydrobenzofuranylacetic acids, pharmaceutical compositions for the treatment of diabetes |
| BR102018007822A2 (pt) | 2017-04-20 | 2018-11-06 | Gilead Sciences, Inc. | composto, métodos para inibir pd-1, pd-l1 e/ou interação de pd-1/pd-l1 e para tratamento de câncer, composição farmacêutica, e, kit para tratamento de ou prevenção de câncer ou uma doença ou condição |
| CN111655678B (zh) * | 2018-01-05 | 2023-08-22 | 广州市恒诺康医药科技有限公司 | 细胞凋亡信号调节激酶-1抑制剂及其应用 |
| TWI707849B (zh) | 2018-02-13 | 2020-10-21 | 美商基利科學股份有限公司 | Pd‐1/pd‐l1抑制劑 |
| JP6626524B2 (ja) | 2018-03-29 | 2019-12-25 | 日本碍子株式会社 | 電気加熱型触媒用担体 |
| KR102591947B1 (ko) | 2018-04-19 | 2023-10-25 | 길리애드 사이언시즈, 인코포레이티드 | Pd-1/pd-l1 억제제 |
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| US11236085B2 (en) | 2018-10-24 | 2022-02-01 | Gilead Sciences, Inc. | PD-1/PD-L1 inhibitors |
| CN110105193B (zh) * | 2019-05-31 | 2022-03-22 | 杭州科耀医药科技有限公司 | 一种2-卤-5-溴苯甲酸的合成方法 |
| WO2025082467A1 (zh) * | 2023-10-19 | 2025-04-24 | 成都先导药物开发股份有限公司 | 一种免疫调节剂 |
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| AU2003277576A1 (en) * | 2002-11-08 | 2004-06-07 | Takeda Pharmaceutical Company Limited | Receptor function controlling agent |
| CN1735408A (zh) * | 2002-11-08 | 2006-02-15 | 武田药品工业株式会社 | 受体机能调节剂 |
| EP1630152A4 (en) * | 2003-05-30 | 2009-09-23 | Takeda Pharmaceutical | CONDENSED CYCLIC COMPOUND |
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| JP4074616B2 (ja) * | 2003-12-25 | 2008-04-09 | 武田薬品工業株式会社 | 3−(4−ベンジルオキシフェニル)プロパン酸誘導体 |
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| JP5299810B2 (ja) * | 2004-02-27 | 2013-09-25 | アムジエン・インコーポレーテツド | 代謝疾患の治療に使用するための、化合物、薬学的組成物及び方法 |
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| CA2646430A1 (en) * | 2006-03-14 | 2007-09-20 | Amgen Inc. | Bicyclic carboxylic acid derivatives useful for treating metabolic disorders |
| TW200815377A (en) | 2006-04-24 | 2008-04-01 | Astellas Pharma Inc | Oxadiazolidinedione compound |
| BRPI0713378A8 (pt) * | 2006-06-27 | 2018-01-02 | Takeda Pharmaceutical | composto, pró-droga, modulador da função do receptor gpr40, agente farmacêutico uso do composto, e, método de produção de uma forma opticamente ativa de um composto |
| CA2662305C (en) | 2006-09-07 | 2012-04-17 | Amgen Inc. | Heterocyclic gpr40 modulators |
| EP2139843B1 (en) * | 2007-04-16 | 2013-12-25 | Amgen, Inc | Substituted biphenyl phenoxy-, thiophenyl- and aminophenylpropanoic acid gpr40 modulators |
| PE20090595A1 (es) | 2007-08-15 | 2009-06-06 | Glaxo Group Ltd | Derivados de quinoliniloxipiperidina y pirrolidina como antagonistas del receptor h1 |
| CA2703217A1 (en) * | 2007-10-29 | 2009-05-07 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| EP2423176A4 (en) * | 2009-04-22 | 2012-11-07 | Astellas Pharma Inc | CARBOXYLIC ACID COMPOUND |
| WO2010143733A1 (en) | 2009-06-09 | 2010-12-16 | Takeda Pharmaceutical Company Limited | Novel fused cyclic compound and use thereof |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
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Also Published As
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| CN105209448B (zh) | 2018-09-14 |
| EP2963027A1 (en) | 2016-01-06 |
| EP2963027B1 (en) | 2018-12-26 |
| JP6387023B2 (ja) | 2018-09-05 |
| CN108017603A (zh) | 2018-05-11 |
| CN105209448A (zh) | 2015-12-30 |
| CN108017603B (zh) | 2021-07-23 |
| EP2963027A4 (en) | 2016-07-20 |
| KR101735787B1 (ko) | 2017-05-16 |
| KR20140108179A (ko) | 2014-09-05 |
| AU2014221489A1 (en) | 2015-10-08 |
| AU2014221489B2 (en) | 2018-03-08 |
| JP2016513135A (ja) | 2016-05-12 |
| US20160009677A1 (en) | 2016-01-14 |
| US9643946B2 (en) | 2017-05-09 |
| CA2900348A1 (en) | 2014-09-04 |
| WO2014133361A1 (ko) | 2014-09-04 |
| CA2900348C (en) | 2021-06-22 |
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