NO326688B1 - Heterocyklisk forbindelse og anvendelse av denne, samt farmasoytisk sammensetning omfattende forbindelsen - Google Patents
Heterocyklisk forbindelse og anvendelse av denne, samt farmasoytisk sammensetning omfattende forbindelsen Download PDFInfo
- Publication number
- NO326688B1 NO326688B1 NO20035331A NO20035331A NO326688B1 NO 326688 B1 NO326688 B1 NO 326688B1 NO 20035331 A NO20035331 A NO 20035331A NO 20035331 A NO20035331 A NO 20035331A NO 326688 B1 NO326688 B1 NO 326688B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- tetrahydroisoquinoline
- alkyl
- carboxylic acid
- ethoxy
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 211
- 150000002391 heterocyclic compounds Chemical class 0.000 title claims abstract description 68
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 184
- 150000003839 salts Chemical class 0.000 claims abstract description 81
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 27
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 27
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 24
- 238000011321 prophylaxis Methods 0.000 claims abstract description 17
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 239000003814 drug Substances 0.000 claims abstract description 16
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 16
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims abstract description 12
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims abstract description 12
- 208000002249 Diabetes Complications Diseases 0.000 claims abstract description 11
- 206010012655 Diabetic complications Diseases 0.000 claims abstract description 10
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 10
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims abstract description 9
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 7
- 229940121363 anti-inflammatory agent Drugs 0.000 claims abstract description 7
- 239000000883 anti-obesity agent Substances 0.000 claims abstract description 7
- 239000003472 antidiabetic agent Substances 0.000 claims abstract description 7
- 229940125710 antiobesity agent Drugs 0.000 claims abstract description 7
- 229940126904 hypoglycaemic agent Drugs 0.000 claims abstract description 7
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 186
- -1 2-(2-hexynoyl)-7-[2-(5-methyl-2-(1-penten-1-yl)oxazol-4-yl)ethoxy]-1,2,3,4-tetrahydroisoquinoline Chemical compound 0.000 claims description 157
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 91
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 76
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 125000005843 halogen group Chemical group 0.000 claims description 27
- 229910052736 halogen Inorganic materials 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 23
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000004434 sulfur atom Chemical group 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 13
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 12
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims description 7
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 6
- 239000003524 antilipemic agent Substances 0.000 claims description 6
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 5
- 208000008589 Obesity Diseases 0.000 claims description 5
- 235000020824 obesity Nutrition 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 4
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 201000001421 hyperglycemia Diseases 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 239000008177 pharmaceutical agent Substances 0.000 claims description 3
- HHXCAGAATHZGLF-VZMAFGJQSA-N 1-[7-[2-[2-[(E)-hex-1-enyl]-1,3-oxazol-4-yl]ethoxy]-3,4-dihydro-1H-isoquinolin-2-yl]hexa-2,4-dien-1-one Chemical compound C(C=CC=CC)(=O)N1CC2=CC(=CC=C2CC1)OCCC=1N=C(OC=1)\C=C\CCCC HHXCAGAATHZGLF-VZMAFGJQSA-N 0.000 claims 1
- 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 abstract description 17
- 239000008103 glucose Substances 0.000 abstract description 17
- 230000000055 hyoplipidemic effect Effects 0.000 abstract description 7
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 6
- 239000003623 enhancer Substances 0.000 abstract description 5
- 229910052799 carbon Inorganic materials 0.000 abstract description 4
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 101150068327 RER1 gene Proteins 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 267
- 239000000203 mixture Substances 0.000 description 109
- 238000005160 1H NMR spectroscopy Methods 0.000 description 90
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 89
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 54
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 53
- 238000006243 chemical reaction Methods 0.000 description 50
- 239000000243 solution Substances 0.000 description 48
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 42
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical class CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 39
- 238000004519 manufacturing process Methods 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- 239000011734 sodium Substances 0.000 description 31
- 238000005481 NMR spectroscopy Methods 0.000 description 30
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- 238000004440 column chromatography Methods 0.000 description 23
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 238000012360 testing method Methods 0.000 description 20
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 18
- 125000004432 carbon atom Chemical group C* 0.000 description 17
- 238000001816 cooling Methods 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 210000004369 blood Anatomy 0.000 description 14
- 239000008280 blood Substances 0.000 description 14
- 238000010898 silica gel chromatography Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 12
- 239000007832 Na2SO4 Substances 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- BWKMGYQJPOAASG-VIFPVBQESA-N (3s)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CN[C@H](C(=O)O)CC2=C1 BWKMGYQJPOAASG-VIFPVBQESA-N 0.000 description 10
- 239000003638 chemical reducing agent Substances 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 235000011181 potassium carbonates Nutrition 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 125000003342 alkenyl group Chemical group 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- PLUBXMRUUVWRLT-UHFFFAOYSA-N Ethyl methanesulfonate Chemical compound CCOS(C)(=O)=O PLUBXMRUUVWRLT-UHFFFAOYSA-N 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 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 6
- 239000007810 chemical reaction solvent Substances 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 230000002218 hypoglycaemic effect Effects 0.000 description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229920000609 methyl cellulose Polymers 0.000 description 6
- 239000001923 methylcellulose Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 239000002198 insoluble material Substances 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 5
- YEKUWOWHPVKTCQ-UHFFFAOYSA-M tetraethylazanium;fluoride;hydrate Chemical compound O.[F-].CC[N+](CC)(CC)CC YEKUWOWHPVKTCQ-UHFFFAOYSA-M 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- GRTWTVFDPBKQNU-MQQKCMAXSA-N (2e,4e)-hexa-2,4-dienoyl chloride Chemical compound C\C=C\C=C\C(Cl)=O GRTWTVFDPBKQNU-MQQKCMAXSA-N 0.000 description 4
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 4
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 4
- 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 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
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- 229910052744 lithium Inorganic materials 0.000 description 4
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- 238000010998 test method Methods 0.000 description 4
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- 125000006023 1-pentenyl group Chemical group 0.000 description 3
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- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 3
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 3
- 125000006043 5-hexenyl group Chemical group 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
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- 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 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
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- 241000978776 Senegalia senegal Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 3
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Classifications
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
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- Organic Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2001161489 | 2001-05-29 | ||
| PCT/JP2002/005097 WO2002096880A1 (fr) | 2001-05-29 | 2002-05-27 | Nouveau compose heterocyclique et son utilisation medicinale |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20035331D0 NO20035331D0 (no) | 2003-11-28 |
| NO326688B1 true NO326688B1 (no) | 2009-01-26 |
Family
ID=19004756
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20035331A NO326688B1 (no) | 2001-05-29 | 2003-11-28 | Heterocyklisk forbindelse og anvendelse av denne, samt farmasoytisk sammensetning omfattende forbindelsen |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US7557123B2 (cs) |
| EP (1) | EP1403253A4 (cs) |
| JP (1) | JP4279136B2 (cs) |
| KR (2) | KR100898358B1 (cs) |
| CN (1) | CN1242994C (cs) |
| AR (1) | AR036036A1 (cs) |
| AU (1) | AU2002308889B2 (cs) |
| BR (1) | BR0209711A (cs) |
| CA (1) | CA2448634A1 (cs) |
| CO (1) | CO5540342A2 (cs) |
| CZ (1) | CZ20033450A3 (cs) |
| HK (1) | HK1069385A1 (cs) |
| HU (1) | HUP0401862A3 (cs) |
| IL (1) | IL159085A0 (cs) |
| MX (1) | MXPA03010811A (cs) |
| NO (1) | NO326688B1 (cs) |
| NZ (1) | NZ530358A (cs) |
| PL (1) | PL367639A1 (cs) |
| RU (1) | RU2299197C2 (cs) |
| TW (1) | TWI297008B (cs) |
| WO (1) | WO2002096880A1 (cs) |
| YU (1) | YU94003A (cs) |
| ZA (1) | ZA200309757B (cs) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1398313A4 (en) | 2001-05-29 | 2005-11-16 | Kyoto Pharma Ind | NEW HETEROCYCLIC DERIVATIVES AND THEIR MEDICAL USE |
| US7816385B2 (en) * | 2002-12-20 | 2010-10-19 | High Point Pharmaceuticals, Llc | Dimeric dicarboxylic acid derivatives, their preparation and use |
| US7718377B2 (en) | 2003-05-29 | 2010-05-18 | Kyoto Pharmaceutical Industries, Ltd. | Insulin resistance curative and method of screening the same |
| TWI359810B (en) | 2004-11-04 | 2012-03-11 | Mitsubishi Tanabe Pharma Corp | Carboxylic acid derivative containing thiazole rin |
| US7790745B2 (en) | 2005-10-21 | 2010-09-07 | Bristol-Myers Squibb Company | Tetrahydroisoquinoline LXR Modulators |
| WO2007058504A1 (en) * | 2005-11-21 | 2007-05-24 | Lg Life Sciences, Ltd. | Novel compounds as agonist for ppar gamma and ppar alpha, method for preparation of the same, and pharmaceutical composition containing the same |
| JPWO2012033195A1 (ja) * | 2010-09-10 | 2014-01-20 | 京都薬品工業株式会社 | 複素環化合物 |
| CN102807526B (zh) * | 2011-06-21 | 2015-12-02 | 寿光富康制药有限公司 | 组蛋白去乙酰化酶抑制剂ZYJ-D08a及其差向异构体的制备方法与应用 |
| WO2020013116A1 (ja) * | 2018-07-10 | 2020-01-16 | 京都薬品工業株式会社 | Ｐｔｐ－１ｂ阻害剤およびその用途 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6051189A (ja) | 1983-08-30 | 1985-03-22 | Sankyo Co Ltd | チアゾリジン誘導体およびその製造法 |
| AR240698A1 (es) | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
| EP0842925A1 (en) | 1987-09-04 | 1998-05-20 | Beecham Group Plc | Substituted thiazolidinedione derivatives |
| US5246943A (en) * | 1992-05-19 | 1993-09-21 | Warner-Lambert Company | Substituted 1,2,3,4-tetahydroisoquinolines with angiotensin II receptor antagonist properties |
| GB9604242D0 (en) | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
| JP2000515501A (ja) * | 1996-07-01 | 2000-11-21 | イーライ・リリー・アンド・カンパニー | 低血糖化および低脂血化用化合物群 |
| JP2000515133A (ja) | 1996-07-01 | 2000-11-14 | イーライ・リリー・アンド・カンパニー | 血糖降下性および脂質低下性の化合物 |
| GB9817118D0 (en) | 1998-08-07 | 1998-10-07 | Glaxo Group Ltd | Pharmaceutical compounds |
| PL356769A1 (en) * | 1999-12-03 | 2004-07-12 | Kyoto Pharmaceutical Industries, Ltd. | Novel heterocyclic compounds and salts thereof and medicinal use of the same |
| US20020037897A1 (en) | 2000-08-07 | 2002-03-28 | 3-Dimensional Pharmaceuticals, Inc. | Tetrahydroisoquinoline-3-carboxylic acid alkoxyguanidines as integrin antagonists |
| EP1398313A4 (en) * | 2001-05-29 | 2005-11-16 | Kyoto Pharma Ind | NEW HETEROCYCLIC DERIVATIVES AND THEIR MEDICAL USE |
-
2002
- 2002-05-27 PL PL02367639A patent/PL367639A1/xx unknown
- 2002-05-27 AU AU2002308889A patent/AU2002308889B2/en not_active Ceased
- 2002-05-27 CA CA002448634A patent/CA2448634A1/en not_active Abandoned
- 2002-05-27 NZ NZ530358A patent/NZ530358A/en unknown
- 2002-05-27 JP JP2003500060A patent/JP4279136B2/ja not_active Expired - Fee Related
- 2002-05-27 RU RU2003137574/04A patent/RU2299197C2/ru not_active IP Right Cessation
- 2002-05-27 BR BR0209711-7A patent/BR0209711A/pt not_active IP Right Cessation
- 2002-05-27 CN CNB028109643A patent/CN1242994C/zh not_active Expired - Fee Related
- 2002-05-27 HU HU0401862A patent/HUP0401862A3/hu unknown
- 2002-05-27 WO PCT/JP2002/005097 patent/WO2002096880A1/ja active Application Filing
- 2002-05-27 CZ CZ20033450A patent/CZ20033450A3/cs unknown
- 2002-05-27 KR KR1020087023698A patent/KR100898358B1/ko not_active IP Right Cessation
- 2002-05-27 IL IL15908502A patent/IL159085A0/xx unknown
- 2002-05-27 MX MXPA03010811A patent/MXPA03010811A/es active IP Right Grant
- 2002-05-27 YU YU94003A patent/YU94003A/sh unknown
- 2002-05-27 ZA ZA200309757A patent/ZA200309757B/en unknown
- 2002-05-27 KR KR10-2003-7015611A patent/KR20040030647A/ko not_active IP Right Cessation
- 2002-05-27 US US10/478,862 patent/US7557123B2/en not_active Expired - Fee Related
- 2002-05-27 EP EP02774070A patent/EP1403253A4/en not_active Withdrawn
- 2002-05-28 TW TW091111315A patent/TWI297008B/zh active
- 2002-05-29 AR ARP020102002A patent/AR036036A1/es unknown
-
2003
- 2003-11-28 NO NO20035331A patent/NO326688B1/no not_active IP Right Cessation
- 2003-12-29 CO CO03112806A patent/CO5540342A2/es not_active Application Discontinuation
-
2005
- 2005-03-02 HK HK05101815A patent/HK1069385A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| TWI297008B (en) | 2008-05-21 |
| JP4279136B2 (ja) | 2009-06-17 |
| ZA200309757B (en) | 2004-12-22 |
| HK1069385A1 (en) | 2005-05-20 |
| EP1403253A1 (en) | 2004-03-31 |
| NO20035331D0 (no) | 2003-11-28 |
| KR20080093076A (ko) | 2008-10-17 |
| JPWO2002096880A1 (ja) | 2004-09-09 |
| US20040220215A1 (en) | 2004-11-04 |
| MXPA03010811A (es) | 2004-02-27 |
| CA2448634A1 (en) | 2002-12-05 |
| BR0209711A (pt) | 2004-11-03 |
| PL367639A1 (en) | 2005-03-07 |
| IL159085A0 (en) | 2004-05-12 |
| EP1403253A4 (en) | 2005-03-30 |
| RU2299197C2 (ru) | 2007-05-20 |
| AU2002308889B2 (en) | 2007-09-06 |
| KR20040030647A (ko) | 2004-04-09 |
| NZ530358A (en) | 2005-04-29 |
| HUP0401862A3 (en) | 2009-03-30 |
| CN1527819A (zh) | 2004-09-08 |
| CN1242994C (zh) | 2006-02-22 |
| WO2002096880A1 (fr) | 2002-12-05 |
| CZ20033450A3 (cs) | 2004-05-12 |
| CO5540342A2 (es) | 2005-07-29 |
| RU2003137574A (ru) | 2005-05-20 |
| YU94003A (sh) | 2006-08-17 |
| AR036036A1 (es) | 2004-08-04 |
| KR100898358B1 (ko) | 2009-05-20 |
| HUP0401862A2 (hu) | 2004-12-28 |
| US7557123B2 (en) | 2009-07-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |