CS250242B2 - Method of 2,2-imino-bis-ethanol's new benzopyran's or benzofuran's derivatives preparation - Google Patents
Method of 2,2-imino-bis-ethanol's new benzopyran's or benzofuran's derivatives preparation Download PDFInfo
- Publication number
- CS250242B2 CS250242B2 CS849320A CS932084A CS250242B2 CS 250242 B2 CS250242 B2 CS 250242B2 CS 849320 A CS849320 A CS 849320A CS 932084 A CS932084 A CS 932084A CS 250242 B2 CS250242 B2 CS 250242B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- parts
- dihydro
- benzopyran
- formula
- methanol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims abstract description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims description 62
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 title claims 2
- 150000001907 coumarones Chemical class 0.000 title claims 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 65
- 239000002253 acid Substances 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- -1 hydroxy, amino Chemical group 0.000 claims description 38
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 2
- 238000007126 N-alkylation reaction Methods 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 150000003254 radicals Chemical class 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims 1
- 125000003710 aryl alkyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 45
- 239000000543 intermediate Substances 0.000 abstract description 18
- 239000004480 active ingredient Substances 0.000 abstract description 13
- 230000002265 prevention Effects 0.000 abstract description 6
- 230000002792 vascular Effects 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 abstract 1
- 239000012450 pharmaceutical intermediate Substances 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 126
- 239000000243 solution Substances 0.000 description 71
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- 239000003480 eluent Substances 0.000 description 31
- 238000003756 stirring Methods 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 26
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 25
- 239000011541 reaction mixture Substances 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 239000003054 catalyst Substances 0.000 description 18
- 238000010992 reflux Methods 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 229960001701 chloroform Drugs 0.000 description 16
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 13
- 125000001841 imino group Chemical group [H]N=* 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 9
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- 239000012258 stirred mixture Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 241000700199 Cavia porcellus Species 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 5
- SFLFCQJQOIZMHF-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)CCC2=C1 SFLFCQJQOIZMHF-UHFFFAOYSA-N 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 229960001317 isoprenaline Drugs 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 4
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 229960003415 propylparaben Drugs 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 210000005245 right atrium Anatomy 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 210000003437 trachea Anatomy 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- KDLVSGWUKFJFTL-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-2-ylmethanol Chemical compound C1=CC=C2OC(CO)CCC2=C1 KDLVSGWUKFJFTL-UHFFFAOYSA-N 0.000 description 3
- PUMRUSBKNSBTAL-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2-carbaldehyde Chemical compound C1=CC=C2OC(C=O)CCC2=C1 PUMRUSBKNSBTAL-UHFFFAOYSA-N 0.000 description 3
- ZFAWSUFYYPNQLP-UHFFFAOYSA-N 6-nitro-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound [O-][N+](=O)C1=CC=C2OC(C(=O)O)CCC2=C1 ZFAWSUFYYPNQLP-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 244000025254 Cannabis sativa Species 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- OYFPTLYUXQSQBP-UHFFFAOYSA-N ethyl 6-hydroxy-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound OC1=CC=C2OC(C(=O)OCC)CCC2=C1 OYFPTLYUXQSQBP-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 210000002837 heart atrium Anatomy 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 210000005062 tracheal ring Anatomy 0.000 description 3
- AEIOAYTWFRFLHE-UHFFFAOYSA-N (5,7-dimethyl-3,4-dihydro-2h-chromen-2-yl)methanol Chemical compound C1CC(CO)OC2=CC(C)=CC(C)=C21 AEIOAYTWFRFLHE-UHFFFAOYSA-N 0.000 description 2
- QFZTUWOWMRNMAH-UHFFFAOYSA-N 2h-pyran-2-carboxylic acid Chemical compound OC(=O)C1OC=CC=C1 QFZTUWOWMRNMAH-UHFFFAOYSA-N 0.000 description 2
- NIFKRMFHSYHWFV-UHFFFAOYSA-N 3,4,7,8,9,10-hexahydro-2h-benzo[h]chromene-2-carboxylic acid Chemical compound C1CCCC2=C(OC(C(=O)O)CC3)C3=CC=C21 NIFKRMFHSYHWFV-UHFFFAOYSA-N 0.000 description 2
- ZNJANLXCXMVFFI-UHFFFAOYSA-N 6-fluoro-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound FC1=CC=C2OC(C(=O)O)CCC2=C1 ZNJANLXCXMVFFI-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
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- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
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- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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- LBOJFHNOWMUJTL-UHFFFAOYSA-N [2-[[2-(hydroxymethyl)-3,4-dihydrochromen-2-yl]methyl]-3,4-dihydrochromen-2-yl]methanol Chemical compound C1CC2=CC=CC=C2OC1(CO)CC1(CO)OC2=CC=CC=C2CC1 LBOJFHNOWMUJTL-UHFFFAOYSA-N 0.000 description 2
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- 125000001691 aryl alkyl amino group Chemical group 0.000 description 2
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- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
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- FGAKMWCYJLTZCI-UHFFFAOYSA-N ethyl 2-methyl-4-oxo-3h-chromene-2-carboxylate Chemical compound C1=CC=C2OC(C(=O)OCC)(C)CC(=O)C2=C1 FGAKMWCYJLTZCI-UHFFFAOYSA-N 0.000 description 2
- XLTYRVHHKJREDL-UHFFFAOYSA-N ethyl 6-fluoro-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound FC1=CC=C2OC(C(=O)OCC)CCC2=C1 XLTYRVHHKJREDL-UHFFFAOYSA-N 0.000 description 2
- BPUBUJNSCKVPEZ-UHFFFAOYSA-N ethyl 6-nitro-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound [O-][N+](=O)C1=CC=C2OC(C(=O)OCC)CCC2=C1 BPUBUJNSCKVPEZ-UHFFFAOYSA-N 0.000 description 2
- XITBJXYCALBQMU-UHFFFAOYSA-N ethyl 6-phenylmethoxy-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C=1C=C2OC(C(=O)OCC)CCC2=CC=1OCC1=CC=CC=C1 XITBJXYCALBQMU-UHFFFAOYSA-N 0.000 description 2
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- 125000005843 halogen group Chemical group 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
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- HCPOCMMGKBZWSJ-UHFFFAOYSA-N ethyl 3-hydrazinyl-3-oxopropanoate Chemical compound CCOC(=O)CC(=O)NN HCPOCMMGKBZWSJ-UHFFFAOYSA-N 0.000 description 1
- RUFRPJSDDAUGER-UHFFFAOYSA-N ethyl 6-(methanesulfonamido)-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound CS(=O)(=O)NC1=CC=C2OC(C(=O)OCC)CCC2=C1 RUFRPJSDDAUGER-UHFFFAOYSA-N 0.000 description 1
- WQPUWNREVMTLCZ-UHFFFAOYSA-N ethyl 6-amino-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound NC1=CC=C2OC(C(=O)OCC)CCC2=C1 WQPUWNREVMTLCZ-UHFFFAOYSA-N 0.000 description 1
- QZALKCKUFHIUJL-UHFFFAOYSA-N ethyl 6-prop-2-enoxy-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C=CCOC1=CC=C2OC(C(=O)OCC)CCC2=C1 QZALKCKUFHIUJL-UHFFFAOYSA-N 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 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 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- FBAFATDZDUQKNH-UHFFFAOYSA-M iron chloride Chemical compound [Cl-].[Fe] FBAFATDZDUQKNH-UHFFFAOYSA-M 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 1
- 229960002329 methacholine Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- FDNARVXHOMTEIR-UHFFFAOYSA-N methyl 2-formyl-3,4-dihydro-2h-chromene-6-carboxylate Chemical compound O1C(C=O)CCC2=CC(C(=O)OC)=CC=C21 FDNARVXHOMTEIR-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- WLRBSOSDXIVACN-UHFFFAOYSA-N n-(2-formyl-3,4-dihydro-2h-chromen-6-yl)acetamide Chemical compound O1C(C=O)CCC2=CC(NC(=O)C)=CC=C21 WLRBSOSDXIVACN-UHFFFAOYSA-N 0.000 description 1
- SWMQMNFQCMYUGK-UHFFFAOYSA-N n-(2-formyl-3,4-dihydro-2h-chromen-6-yl)methanesulfonamide Chemical compound O1C(C=O)CCC2=CC(NS(=O)(=O)C)=CC=C21 SWMQMNFQCMYUGK-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- UNBUPYAXDFYBDJ-UHFFFAOYSA-N n-[2-(hydroxymethyl)-3,4-dihydro-2h-chromen-6-yl]acetamide Chemical compound O1C(CO)CCC2=CC(NC(=O)C)=CC=C21 UNBUPYAXDFYBDJ-UHFFFAOYSA-N 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000007910 systemic administration Methods 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
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D407/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- 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
- C07D307/81—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- 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
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- 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
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- 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
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/66—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 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 in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- 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
- C07D311/92—Naphthopyrans; Hydrogenated naphthopyrans
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Furan Compounds (AREA)
- Pyrane Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55808183A | 1983-12-05 | 1983-12-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS250242B2 true CS250242B2 (en) | 1987-04-16 |
Family
ID=24228139
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS849320A CS250242B2 (en) | 1983-12-05 | 1984-12-04 | Method of 2,2-imino-bis-ethanol's new benzopyran's or benzofuran's derivatives preparation |
Country Status (32)
| Country | Link |
|---|---|
| EP (1) | EP0145067B1 (es) |
| JP (1) | JPS60132977A (es) |
| KR (1) | KR870000923B1 (es) |
| AR (1) | AR241414A1 (es) |
| AT (1) | ATE40361T1 (es) |
| AU (1) | AU573658B2 (es) |
| BG (1) | BG43866A3 (es) |
| CA (1) | CA1337429C (es) |
| CS (1) | CS250242B2 (es) |
| CY (1) | CY1609A (es) |
| DD (1) | DD235453A5 (es) |
| DE (1) | DE3476388D1 (es) |
| DK (2) | DK165112C (es) |
| DZ (1) | DZ712A1 (es) |
| ES (1) | ES8603870A1 (es) |
| FI (1) | FI82460C (es) |
| GR (1) | GR81098B (es) |
| HK (1) | HK52791A (es) |
| HU (1) | HU202219B (es) |
| IE (1) | IE57831B1 (es) |
| IL (1) | IL73706A (es) |
| MA (1) | MA20292A1 (es) |
| NO (2) | NO169839C (es) |
| NZ (1) | NZ210388A (es) |
| PH (1) | PH22432A (es) |
| PL (1) | PL146342B1 (es) |
| PT (1) | PT79609B (es) |
| RO (1) | RO91184B (es) |
| SG (1) | SG47091G (es) |
| SU (1) | SU1428199A3 (es) |
| ZA (1) | ZA849445B (es) |
| ZW (1) | ZW19784A1 (es) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1337432C (en) * | 1988-03-23 | 1995-10-24 | Raymond M. Xhonneux | Method of lowering the blood pressure |
| JPH02103116U (es) * | 1989-02-01 | 1990-08-16 | ||
| JPH02218675A (ja) * | 1989-02-21 | 1990-08-31 | Nippon Kayaku Co Ltd | ６―フルオロクロモン―２―カルボン酸及びその製造法 |
| IE68675B1 (en) * | 1990-11-01 | 1996-07-10 | Takeda Chemical Industries Ltd | Aminocoumaran derivatives their production and use |
| DE69433401T2 (de) * | 1993-08-19 | 2004-09-16 | Janssen Pharmaceutica N.V. | Gefässverengende dihydrobenzopyranderivate |
| TW355683B (en) * | 1994-02-17 | 1999-04-11 | Janssen Pharmaceutica Nv | Composition containing micronized nebivolol |
| PT707007E (pt) * | 1994-10-14 | 2002-06-28 | Merck Patent Gmbh | Derivados amino(tio)eter como agentes activos no snc |
| JP3454832B2 (ja) * | 1996-06-07 | 2003-10-06 | バンダービルト ユニバーシティ | 抗炎症剤として有用なジヒドロベンゾピランおよび関連化合物 |
| UA62993C2 (en) * | 1997-12-19 | 2004-01-15 | Bayer Ag | CHROMAN DERIVATIVES SUBSTITUTED ON CARBOXYLIC GROUP USED AS AGONISTS OF b-3-ADRENORECEPTOR |
| US6541669B1 (en) | 1998-06-08 | 2003-04-01 | Theravance, Inc. | β2-adrenergic receptor agonists |
| US6713651B1 (en) | 1999-06-07 | 2004-03-30 | Theravance, Inc. | β2-adrenergic receptor agonists |
| US6593497B1 (en) | 1999-06-02 | 2003-07-15 | Theravance, Inc. | β2-adrenergic receptor agonists |
| US6683115B2 (en) | 1999-06-02 | 2004-01-27 | Theravance, Inc. | β2-adrenergic receptor agonists |
| UA73965C2 (en) | 1999-12-08 | 2005-10-17 | Theravance Inc | b2 ADRENERGIC RECEPTOR ANTAGONISTS |
| UA73981C2 (en) | 2000-03-10 | 2005-10-17 | Merck Patent Gmbh | (r)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane for treatment of extrapyramidal movement disorders (variants), pharmaceutical composition and kit |
| DE60233140D1 (de) | 2001-05-02 | 2009-09-10 | Nitromed Inc | Nitrosiertes und nitrosyliertes nebivolol und seine metaboliten, zusammensetzungen und anwendungsverfahren |
| BR0211358A (pt) | 2001-07-26 | 2004-09-21 | Merck Patent Gmbh | Uso do composto de 2-[5-(4-fluorofenil)-3-piridilmetilaminometil]-croman o e seus sais fisiologicamente aceitáveis |
| TWI249515B (en) | 2001-11-13 | 2006-02-21 | Theravance Inc | Aryl aniline beta2 adrenergic receptor agonists |
| US6653323B2 (en) | 2001-11-13 | 2003-11-25 | Theravance, Inc. | Aryl aniline β2 adrenergic receptor agonists |
| HRP20080297T3 (en) * | 2004-07-30 | 2008-07-31 | Torrent Pharmaceuticals Ltd | Nebivolol and its pharmaceutically acceptable salts, process for preparation and pharmaceutical compositions of nebivolol |
| ATE465157T1 (de) * | 2004-08-11 | 2010-05-15 | Hetero Drugs Ltd | Neues verfahren zur herstellung von nebivololzwischenprodukten |
| CN100341866C (zh) * | 2004-08-30 | 2007-10-10 | 中国科学院理化技术研究所 | α，α’－[亚氨基二（亚甲基）]－双－（6－氟－3，4－二氢－2H－1－苯并吡喃－2－甲醇）甲烷磺酸盐的合成方法 |
| JP2008528626A (ja) * | 2005-01-31 | 2008-07-31 | マイラン ラボラトリーズ インク． | ヒドロキシル化されたネビボロールを含む薬学的組成物 |
| JP2008528627A (ja) * | 2005-01-31 | 2008-07-31 | マイラン ラボラトリーズ インク． | グルクロン酸化されたネビボロール代謝産物 |
| EP1850842A1 (de) * | 2005-02-11 | 2007-11-07 | Stada Arzneimittel Ag | Pharmazeutische zusammensetzungen nebivolo und ein hydrophiles polymer |
| AT502220A1 (de) * | 2005-07-19 | 2007-02-15 | Pharmacon Forschung & Beratung | Verfahren zur herstellung von nebivolol |
| US7560575B2 (en) * | 2005-12-28 | 2009-07-14 | Acino Pharma Ag | Process for preparation of racemic Nebivolol |
| EP1803716B1 (en) * | 2005-12-28 | 2012-07-25 | Acino Pharma AG | A process for preparation of racemic nebivolol |
| RU2392277C2 (ru) * | 2005-12-28 | 2010-06-20 | Асино Фарма Аг | Способ получения рацемического небиволола |
| EP1973895A1 (en) | 2006-01-18 | 2008-10-01 | Hetero Drugs Limited | Process for isolation of desired isomers of nebivolol intermediates |
| ITMI20061889A1 (it) | 2006-10-03 | 2008-04-04 | Zambon Spa | Processo di preparazione di nebivololo |
| US7999124B2 (en) | 2006-11-27 | 2011-08-16 | Zach System S.P.A. | Process for preparing nebivolol |
| AU2008209264B2 (en) | 2007-01-22 | 2014-11-27 | Mylan Pharmaceuticals Ulc | Pharmaceutical compositions comprising nebivolol or a nebivolol analogue |
| CN101463024B (zh) | 2007-12-21 | 2011-06-08 | 上海现代制药股份有限公司 | 一种制备rrrs和sssr型的奈必洛尔中间体混合物的方法 |
| ITMI20080547A1 (it) * | 2008-03-31 | 2009-10-01 | Zach System Spa | Processo di preparazione di nebivololo |
| IT1392067B1 (it) * | 2008-10-31 | 2012-02-09 | Zach System Spa | Processo di preparazione di nebivololo |
| IT1395354B1 (it) * | 2009-07-23 | 2012-09-14 | Zach System Spa | Processo di preparazione di nebivololo |
| DE102010005953A1 (de) | 2010-01-27 | 2011-07-28 | Corden PharmaChem GmbH, 68305 | Verfahren zur Herstellung von Nebivolol |
| IT1397962B1 (it) | 2010-02-11 | 2013-02-04 | Menarini Int Operations Lu Sa | Processo per la preparazione del nebivololo. |
| IT1402974B1 (it) | 2010-11-30 | 2013-09-27 | Menarini Int Operations Lu Sa | Processo per la preparazione del nebivololo. |
| ITRM20110418A1 (it) | 2011-08-02 | 2013-02-03 | Menarini Int Operations Lu Sa | Processo per la preparazione di epossidi quali intermedi per la sintesi del nebivololo. |
| EP2907809B1 (en) | 2014-02-14 | 2018-08-22 | Corden Pharma International GmbH | Base-free process for the preparation of ketone intermediates usable for manufacture of nebivolol |
| EP2907810A1 (en) | 2014-02-14 | 2015-08-19 | Corden Pharma International GmbH | A new method for producing nebivolol hydrochloride of high purity |
| DE102014107132A1 (de) | 2014-05-20 | 2015-11-26 | Corden Pharma International Gmbh | Verfahren zur Herstellung von Epoxiden die in der Herstellung von Nebivolol und dessen Derivaten einsetzbar sind |
| ES2901966T3 (es) | 2015-05-19 | 2022-03-24 | Zhejiang Ausun Pharmaceutical Co Ltd | Método de síntesis de nebivolol y compuesto intermedio del mismo |
| CN105085499B (zh) * | 2015-08-07 | 2018-09-25 | 上海现代制药海门有限公司 | 盐酸奈必洛尔中间体混合物的结晶分离方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1054655A (es) * | 1964-01-24 | |||
| US4313955A (en) * | 1980-10-14 | 1982-02-02 | Ciba-Geigy Corporation | 1,5-Bis(1,4-benzodioxin-2-yl)-3-azapentane-1,5-diols |
| GB8418472D0 (en) * | 1984-07-19 | 1984-08-22 | Beecham Group Plc | Compounds |
-
1984
- 1984-11-19 CA CA000468108A patent/CA1337429C/en not_active Expired - Fee Related
- 1984-11-21 PL PL1984250524A patent/PL146342B1/pl unknown
- 1984-11-22 AT AT84201693T patent/ATE40361T1/de not_active IP Right Cessation
- 1984-11-22 EP EP84201693A patent/EP0145067B1/en not_active Expired
- 1984-11-22 DE DE8484201693T patent/DE3476388D1/de not_active Expired
- 1984-11-26 KR KR1019840007404A patent/KR870000923B1/ko not_active Expired
- 1984-11-29 NZ NZ210388A patent/NZ210388A/en unknown
- 1984-11-29 GR GR81098A patent/GR81098B/el unknown
- 1984-11-30 JP JP59252038A patent/JPS60132977A/ja active Granted
- 1984-12-02 DZ DZ847346A patent/DZ712A1/fr active
- 1984-12-03 IL IL73706A patent/IL73706A/xx not_active IP Right Cessation
- 1984-12-03 RO RO116496A patent/RO91184B/ro unknown
- 1984-12-03 AR AR84298819A patent/AR241414A1/es active
- 1984-12-03 DD DD84270216A patent/DD235453A5/de not_active IP Right Cessation
- 1984-12-04 ZW ZW197/84A patent/ZW19784A1/xx unknown
- 1984-12-04 BG BG067765A patent/BG43866A3/xx unknown
- 1984-12-04 MA MA20516A patent/MA20292A1/fr unknown
- 1984-12-04 FI FI844777A patent/FI82460C/fi active IP Right Grant
- 1984-12-04 HU HU844482A patent/HU202219B/hu unknown
- 1984-12-04 NO NO844845A patent/NO169839C/no not_active IP Right Cessation
- 1984-12-04 ES ES538256A patent/ES8603870A1/es not_active Expired
- 1984-12-04 CS CS849320A patent/CS250242B2/cs unknown
- 1984-12-04 SU SU843826501A patent/SU1428199A3/ru active
- 1984-12-04 PT PT79609A patent/PT79609B/pt unknown
- 1984-12-04 ZA ZA849445A patent/ZA849445B/xx unknown
- 1984-12-04 PH PH31525A patent/PH22432A/en unknown
- 1984-12-04 IE IE3103/84A patent/IE57831B1/en not_active IP Right Cessation
- 1984-12-04 DK DK577084A patent/DK165112C/da not_active IP Right Cessation
- 1984-12-05 AU AU36326/84A patent/AU573658B2/en not_active Expired
-
1991
- 1991-06-18 SG SG47091A patent/SG47091G/en unknown
- 1991-07-11 HK HK527/91A patent/HK52791A/en not_active IP Right Cessation
-
1992
- 1992-01-31 DK DK011892A patent/DK165321C/da not_active IP Right Cessation
- 1992-04-03 CY CY1609A patent/CY1609A/xx unknown
-
2004
- 2004-11-26 NO NO2004007C patent/NO2004007I2/no unknown
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