NO311221B1 - Dihydrobenzofuraner - Google Patents
Dihydrobenzofuraner Download PDFInfo
- Publication number
- NO311221B1 NO311221B1 NO19970092A NO970092A NO311221B1 NO 311221 B1 NO311221 B1 NO 311221B1 NO 19970092 A NO19970092 A NO 19970092A NO 970092 A NO970092 A NO 970092A NO 311221 B1 NO311221 B1 NO 311221B1
- Authority
- NO
- Norway
- Prior art keywords
- salts
- compounds
- formula
- pyridines
- cyclopentane
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 95
- -1 2-chloro-6-fluorophenyl Chemical group 0.000 claims description 117
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 48
- 238000011282 treatment Methods 0.000 claims description 16
- 150000001204 N-oxides Chemical class 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 14
- 150000003222 pyridines Chemical class 0.000 claims description 14
- 201000010099 disease Diseases 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 125000000229 (C1-C4)alkoxy group Chemical class 0.000 claims description 12
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical group C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 150000002430 hydrocarbons Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 208000017520 skin disease Diseases 0.000 claims description 5
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 2
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 35
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 22
- 239000002244 precipitate Substances 0.000 description 18
- 239000003921 oil Substances 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000003208 petroleum Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 12
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 10
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 8
- QXOXUEFXRSIYSW-UHFFFAOYSA-N methyl 3-hydroxy-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(O)=C1 QXOXUEFXRSIYSW-UHFFFAOYSA-N 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- IUVCFHHAEHNCFT-INIZCTEOSA-N 2-[(1s)-1-[4-amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one Chemical compound C1=C(F)C(OC(C)C)=CC=C1C(C1=C(N)N=CN=C11)=NN1[C@@H](C)C1=C(C=2C=C(F)C=CC=2)C(=O)C2=CC(F)=CC=C2O1 IUVCFHHAEHNCFT-INIZCTEOSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012188 paraffin wax Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- 208000010668 atopic eczema Diseases 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 150000003527 tetrahydropyrans Chemical group 0.000 description 5
- 102000003390 tumor necrosis factor Human genes 0.000 description 5
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 4
- HUWJPQOEEOZWAI-UHFFFAOYSA-N 7-methoxy-2,2-dimethyl-3h-1-benzofuran-4-carboxylic acid Chemical compound COC1=CC=C(C(O)=O)C2=C1OC(C)(C)C2 HUWJPQOEEOZWAI-UHFFFAOYSA-N 0.000 description 4
- 230000000172 allergic effect Effects 0.000 description 4
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 210000000440 neutrophil Anatomy 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- PGZSNCSZHYPPFT-UHFFFAOYSA-N 2,2-diethyl-7-methoxy-3h-1-benzofuran-4-carboxylic acid Chemical compound COC1=CC=C(C(O)=O)C2=C1OC(CC)(CC)C2 PGZSNCSZHYPPFT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000000460 chlorine Substances 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
- 239000012230 colorless oil Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- LSEFCHWGJNHZNT-UHFFFAOYSA-M methyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 LSEFCHWGJNHZNT-UHFFFAOYSA-M 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- AXDZFGRFZOQVBV-UHFFFAOYSA-N 2-chlorocyclopentan-1-one Chemical compound ClC1CCCC1=O AXDZFGRFZOQVBV-UHFFFAOYSA-N 0.000 description 2
- FKBDCQZCTTVQJY-UHFFFAOYSA-N 7-methoxyspiro[3H-1-benzofuran-2,4'-oxane] Chemical compound COC1=CC=CC=2CC3(CCOCC3)OC=21 FKBDCQZCTTVQJY-UHFFFAOYSA-N 0.000 description 2
- GXWIGFLYSYMGGY-UHFFFAOYSA-N 7-methoxyspiro[3h-1-benzofuran-2,1'-cyclopentane] Chemical compound O1C=2C(OC)=CC=CC=2CC21CCCC2 GXWIGFLYSYMGGY-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010044467 Isoenzymes Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 108010008211 N-Formylmethionine Leucyl-Phenylalanine Proteins 0.000 description 2
- PRQROPMIIGLWRP-UHFFFAOYSA-N N-formyl-methionyl-leucyl-phenylalanin Chemical compound CSCCC(NC=O)C(=O)NC(CC(C)C)C(=O)NC(C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-UHFFFAOYSA-N 0.000 description 2
- 241000272108 Ophiophagus hannah Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010038419 Renal colic Diseases 0.000 description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 206010000496 acne Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 229940054066 benzamide antipsychotics Drugs 0.000 description 2
- 150000003936 benzamides Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- LUQWEWUOJZERPH-UHFFFAOYSA-N ethyl 3-(2-oxocyclopentyl)oxy-4-phenylmethoxybenzoate Chemical compound C1CCC(=O)C1OC1=CC(C(=O)OCC)=CC=C1OCC1=CC=CC=C1 LUQWEWUOJZERPH-UHFFFAOYSA-N 0.000 description 2
- 210000001508 eye Anatomy 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 210000004969 inflammatory cell Anatomy 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
- 150000002617 leukotrienes Chemical class 0.000 description 2
- 229940126601 medicinal product Drugs 0.000 description 2
- RIEKUNSZSAGWMV-UHFFFAOYSA-N methyl 2,2-diethyl-7-methoxy-3h-1-benzofuran-4-carboxylate Chemical compound COC1=CC=C(C(=O)OC)C2=C1OC(CC)(CC)C2 RIEKUNSZSAGWMV-UHFFFAOYSA-N 0.000 description 2
- QCMPNJYNLIXTAV-UHFFFAOYSA-N methyl 2-(cyclopenten-1-ylmethyl)-3-hydroxy-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(O)=C1CC1=CCCC1 QCMPNJYNLIXTAV-UHFFFAOYSA-N 0.000 description 2
- UHIQYEXOLZWDMA-UHFFFAOYSA-N methyl 3-hydroxy-4-methoxy-2-(2-methylprop-2-enyl)benzoate Chemical compound COC(=O)C1=CC=C(OC)C(O)=C1CC(C)=C UHIQYEXOLZWDMA-UHFFFAOYSA-N 0.000 description 2
- QRPKSNHNJKTEDF-UHFFFAOYSA-N methyl 4-methoxy-3-(2-methylidenecyclopentyl)oxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(OC2C(CCC2)=C)=C1 QRPKSNHNJKTEDF-UHFFFAOYSA-N 0.000 description 2
- YVGQCNIKPHOYLZ-UHFFFAOYSA-N methyl 4-methoxy-3-(2-methylprop-2-enoxy)benzoate Chemical compound COC(=O)C1=CC=C(OC)C(OCC(C)=C)=C1 YVGQCNIKPHOYLZ-UHFFFAOYSA-N 0.000 description 2
- OMTDRCNBFRTEGC-UHFFFAOYSA-N methyl 4-methoxy-3-(2-oxocyclopentyl)oxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(OC2C(CCC2)=O)=C1 OMTDRCNBFRTEGC-UHFFFAOYSA-N 0.000 description 2
- RFOUCWBINJFMGT-UHFFFAOYSA-N methyl 4-methoxy-3-(3-oxopentan-2-yloxy)benzoate Chemical compound CCC(=O)C(C)OC1=CC(C(=O)OC)=CC=C1OC RFOUCWBINJFMGT-UHFFFAOYSA-N 0.000 description 2
- MOUBGAIELHXPHW-UHFFFAOYSA-N methyl 4-methoxy-3-(4-oxooxan-3-yl)oxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C(OC2C(CCOC2)=O)=C1 MOUBGAIELHXPHW-UHFFFAOYSA-N 0.000 description 2
- DURMMKABWKJCRM-UHFFFAOYSA-N methyl 7-methoxy-2,2-dimethyl-3h-1-benzofuran-4-carboxylate Chemical compound COC(=O)C1=CC=C(OC)C2=C1CC(C)(C)O2 DURMMKABWKJCRM-UHFFFAOYSA-N 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
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- 206010039083 rhinitis Diseases 0.000 description 2
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- 239000000377 silicon dioxide Substances 0.000 description 2
- CRLYHSUSQLYCCZ-UHFFFAOYSA-M sodium;azanide;methyl(triphenyl)phosphanium;bromide Chemical compound [NH2-].[Na+].[Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 CRLYHSUSQLYCCZ-UHFFFAOYSA-M 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- HJMQDJPMQIHLPB-UHFFFAOYSA-N zardaverine Chemical compound C1=C(OC(F)F)C(OC)=CC(C2=NNC(=O)C=C2)=C1 HJMQDJPMQIHLPB-UHFFFAOYSA-N 0.000 description 2
- 229950001080 zardaverine Drugs 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 1
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 description 1
- JDMFXJULNGEPOI-UHFFFAOYSA-N 2,6-dichloroaniline Chemical compound NC1=C(Cl)C=CC=C1Cl JDMFXJULNGEPOI-UHFFFAOYSA-N 0.000 description 1
- ODUZJBKKYBQIBX-UHFFFAOYSA-N 2,6-difluoroaniline Chemical compound NC1=C(F)C=CC=C1F ODUZJBKKYBQIBX-UHFFFAOYSA-N 0.000 description 1
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 1
- YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Saccharide Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH232394 | 1994-07-22 | ||
| PCT/EP1995/002841 WO1996003399A1 (de) | 1994-07-22 | 1995-07-19 | Dihydrobenzofurane |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO970092D0 NO970092D0 (no) | 1997-01-09 |
| NO970092L NO970092L (no) | 1997-01-09 |
| NO311221B1 true NO311221B1 (no) | 2001-10-29 |
Family
ID=4231132
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19970092A NO311221B1 (no) | 1994-07-22 | 1997-01-09 | Dihydrobenzofuraner |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6121274A (ko) |
| EP (1) | EP0772610B9 (ko) |
| JP (1) | JP4146894B2 (ko) |
| KR (1) | KR100381584B1 (ko) |
| CN (1) | CN1068879C (ko) |
| AT (1) | ATE196765T1 (ko) |
| AU (1) | AU702346B2 (ko) |
| CZ (1) | CZ291758B6 (ko) |
| DE (1) | DE59508773D1 (ko) |
| DK (1) | DK0772610T3 (ko) |
| ES (1) | ES2152414T3 (ko) |
| FI (1) | FI970246A0 (ko) |
| GR (1) | GR3034991T3 (ko) |
| HU (1) | HU221504B (ko) |
| MX (1) | MX9700557A (ko) |
| NO (1) | NO311221B1 (ko) |
| NZ (1) | NZ290420A (ko) |
| PL (1) | PL185683B1 (ko) |
| PT (1) | PT772610E (ko) |
| RU (1) | RU2138498C1 (ko) |
| SK (1) | SK281857B6 (ko) |
| WO (1) | WO1996003399A1 (ko) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6514996B2 (en) | 1995-05-19 | 2003-02-04 | Kyowa Hakko Kogyo Co., Ltd. | Derivatives of benzofuran or benzodioxole |
| DK0771794T3 (da) * | 1995-05-19 | 2006-09-11 | Kyowa Hakko Kogyo Kk | Oxygenholdige heterocykliske forbindelser |
| JP2000501411A (ja) * | 1995-12-05 | 2000-02-08 | ダーウィン・ディスカバリー・リミテッド | ベンゾフランカルボキサミドおよびスルホンアミド |
| ATE228131T1 (de) * | 1996-05-15 | 2002-12-15 | Altana Pharma Ag | Imidazopyridine |
| IL126558A (en) * | 1996-05-20 | 2002-07-25 | Darwin Discovery Ltd | Benzofuran carboxamides and pharmaceutical compositions containing them |
| DE19628621A1 (de) * | 1996-07-16 | 1998-01-22 | Byk Gulden Lomberg Chem Fab | Neue 4-substituierte Benzofurane |
| DE19628622A1 (de) * | 1996-07-16 | 1998-01-22 | Byk Gulden Lomberg Chem Fab | Neue 5-substituierte [2H] Chromene |
| DE69717827T2 (de) * | 1996-08-19 | 2003-09-04 | Altana Pharma Ag | Benzofuran-4-carboxamide |
| AU5652698A (en) * | 1996-11-12 | 1998-06-03 | Byk Gulden Lomberg Chemische Fabrik Gmbh | (2,3-dihydrobenzofuranyl)-thiazoles as phosphodiesterase inhibitors |
| EP0941221B1 (en) * | 1996-11-20 | 2003-02-26 | ALTANA Pharma AG | Substituted dihydrobenzofurans as pde inhibitors |
| AU753576B2 (en) * | 1997-12-15 | 2002-10-24 | Altana Pharma Ag | Dihydrobenzofurans |
| GB2333041A (en) * | 1998-01-13 | 1999-07-14 | Johnson & Johnson Medical Ltd | Wound Composition |
| EE04641B1 (et) * | 1998-05-05 | 2006-06-15 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Bensimidasoolid ja bensoksasoolid, nende kasutamine hingamisteede ja dermatooside raviks ette nähtud ravimite valmistamiseks ning neid sisaldav ravim |
| SI1086096T1 (en) | 1998-06-10 | 2003-12-31 | Altana Pharma Ag | Benzamides with tetrahydrofuranyloxy substitutents as phosphodiesterase 4 inhibitors |
| PT1212089E (pt) | 1999-08-21 | 2006-08-31 | Altana Pharma Ag | Combinacao sinergica de roflumilast e salmeterol |
| GB0003257D0 (en) | 2000-02-11 | 2000-04-05 | Darwin Discovery Ltd | Heterocyclic compounds and their therapeutic use |
| CN1646118A (zh) * | 2002-03-29 | 2005-07-27 | 中外制药株式会社 | 预防或治疗呼吸系统疾病的药物组合物 |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| JPWO2007052794A1 (ja) * | 2005-11-04 | 2009-04-30 | 日本曹達株式会社 | オルト置換アニリン誘導体及び抗酸化薬 |
| US7842713B2 (en) * | 2006-04-20 | 2010-11-30 | Pfizer Inc | Fused phenyl amido heterocyclic compounds |
| ES2374337T3 (es) | 2007-05-16 | 2012-02-15 | Nycomed Gmbh | Derivados de pirazolona como inhibidores de pde4. |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| CA3089569C (en) | 2007-06-04 | 2023-12-05 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US20100120694A1 (en) | 2008-06-04 | 2010-05-13 | Synergy Pharmaceuticals, Inc. | Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders |
| EP2321341B1 (en) | 2008-07-16 | 2017-02-22 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| NZ591366A (en) | 2008-09-11 | 2012-05-25 | Pfizer | Heteroaryls amide derivatives and their use as glucokinase activators |
| KR101295937B1 (ko) * | 2009-03-11 | 2013-08-14 | 화이자 인코포레이티드 | 글루코카이네이즈 억제제로서 사용되는 벤조푸라닐 유도체 |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| CN108676076A (zh) | 2011-03-01 | 2018-10-19 | 辛纳吉制药公司 | 制备鸟苷酸环化酶c激动剂的方法 |
| CN103429581B (zh) * | 2012-01-12 | 2015-08-26 | 江苏恒瑞医药股份有限公司 | 多环类衍生物、其制备方法及其在医药上的应用 |
| JP6499591B2 (ja) | 2013-02-25 | 2019-04-10 | シナジー ファーマシューティカルズ インコーポレイテッド | 結腸洗浄において用いるためのグアニル酸シクラーゼ受容体アゴニスト |
| EP2970384A1 (en) | 2013-03-15 | 2016-01-20 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| JP2016514670A (ja) | 2013-03-15 | 2016-05-23 | シナジー ファーマシューティカルズ インコーポレイテッド | 他の薬物と組み合わせたグアニル酸シクラーゼ受容体アゴニスト |
| RS65632B1 (sr) | 2013-06-05 | 2024-07-31 | Bausch Health Ireland Ltd | Ultra-prečišćeni agonisti guanilat-ciklaze c, postupak njihove pripreme i upotrebe |
| WO2015021358A2 (en) | 2013-08-09 | 2015-02-12 | Dominique Charmot | Compounds and methods for inhibiting phosphate transport |
| TW202400564A (zh) | 2015-06-05 | 2024-01-01 | 美商艾佛艾姆希公司 | 作為除草劑之嘧啶氧基苯衍生物 |
| JP2022533251A (ja) | 2019-05-21 | 2022-07-21 | アルデリックス， インコーポレイテッド | 患者において血清リン酸塩を低下させるための組み合わせ |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE71647B1 (en) * | 1991-01-28 | 1997-02-26 | Rhone Poulenc Rorer Ltd | Benzamide derivatives |
| GB9212693D0 (en) * | 1992-06-15 | 1992-07-29 | Celltech Ltd | Chemical compounds |
| CA2114114C (en) * | 1992-06-15 | 2005-05-03 | Nigel Robert Arnold Beeley | Trisubstituted phenyl derivatives as selective phosphodiesterase iv inhibitors |
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1995
- 1995-07-19 MX MX9700557A patent/MX9700557A/es not_active IP Right Cessation
- 1995-07-19 PL PL95318297A patent/PL185683B1/pl not_active IP Right Cessation
- 1995-07-19 AT AT95926953T patent/ATE196765T1/de not_active IP Right Cessation
- 1995-07-19 CN CN95195177A patent/CN1068879C/zh not_active Expired - Fee Related
- 1995-07-19 KR KR1019970700420A patent/KR100381584B1/ko not_active IP Right Cessation
- 1995-07-19 ES ES95926953T patent/ES2152414T3/es not_active Expired - Lifetime
- 1995-07-19 AU AU31153/95A patent/AU702346B2/en not_active Ceased
- 1995-07-19 NZ NZ290420A patent/NZ290420A/xx not_active IP Right Cessation
- 1995-07-19 JP JP50543996A patent/JP4146894B2/ja not_active Expired - Lifetime
- 1995-07-19 RU RU97102828A patent/RU2138498C1/ru not_active IP Right Cessation
- 1995-07-19 WO PCT/EP1995/002841 patent/WO1996003399A1/de active IP Right Grant
- 1995-07-19 CZ CZ1997188A patent/CZ291758B6/cs not_active IP Right Cessation
- 1995-07-19 DK DK95926953T patent/DK0772610T3/da active
- 1995-07-19 HU HU9700022A patent/HU221504B/hu not_active IP Right Cessation
- 1995-07-19 PT PT95926953T patent/PT772610E/pt unknown
- 1995-07-19 DE DE59508773T patent/DE59508773D1/de not_active Expired - Lifetime
- 1995-07-19 US US08/750,920 patent/US6121274A/en not_active Expired - Lifetime
- 1995-07-19 EP EP95926953A patent/EP0772610B9/de not_active Expired - Lifetime
- 1995-07-19 SK SK2-97A patent/SK281857B6/sk not_active IP Right Cessation
-
1997
- 1997-01-09 NO NO19970092A patent/NO311221B1/no not_active IP Right Cessation
- 1997-01-21 FI FI970246A patent/FI970246A0/fi unknown
-
2000
- 2000-12-05 GR GR20000402680T patent/GR3034991T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NZ290420A (en) | 1999-01-28 |
| DK0772610T3 (da) | 2001-01-29 |
| ATE196765T1 (de) | 2000-10-15 |
| PT772610E (pt) | 2001-03-30 |
| NO970092D0 (no) | 1997-01-09 |
| DE59508773D1 (de) | 2000-11-09 |
| HU9700022D0 (en) | 1997-02-28 |
| SK297A3 (en) | 1997-08-06 |
| EP0772610A1 (de) | 1997-05-14 |
| HUT77925A (hu) | 1998-11-30 |
| ES2152414T3 (es) | 2001-02-01 |
| JPH10503484A (ja) | 1998-03-31 |
| GR3034991T3 (en) | 2001-03-30 |
| AU3115395A (en) | 1996-02-22 |
| MX9700557A (es) | 1997-12-31 |
| RU2138498C1 (ru) | 1999-09-27 |
| PL185683B1 (pl) | 2003-07-31 |
| FI970246A (fi) | 1997-01-21 |
| NO970092L (no) | 1997-01-09 |
| CZ18897A3 (en) | 1997-09-17 |
| PL318297A1 (en) | 1997-06-09 |
| CN1159804A (zh) | 1997-09-17 |
| EP0772610B9 (de) | 2001-07-25 |
| WO1996003399A1 (de) | 1996-02-08 |
| EP0772610B1 (de) | 2000-10-04 |
| KR100381584B1 (ko) | 2003-08-21 |
| FI970246A0 (fi) | 1997-01-21 |
| CZ291758B6 (cs) | 2003-05-14 |
| US6121274A (en) | 2000-09-19 |
| HU221504B (en) | 2002-10-28 |
| AU702346B2 (en) | 1999-02-18 |
| CN1068879C (zh) | 2001-07-25 |
| SK281857B6 (sk) | 2001-08-06 |
| JP4146894B2 (ja) | 2008-09-10 |
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Legal Events
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| MM1K | Lapsed by not paying the annual fees |