JPH0617345B2 - 化合物およびその製造方法 - Google Patents
化合物およびその製造方法Info
- Publication number
- JPH0617345B2 JPH0617345B2 JP56503727A JP50372781A JPH0617345B2 JP H0617345 B2 JPH0617345 B2 JP H0617345B2 JP 56503727 A JP56503727 A JP 56503727A JP 50372781 A JP50372781 A JP 50372781A JP H0617345 B2 JPH0617345 B2 JP H0617345B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- carbon atoms
- compound
- acid
- ethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims description 75
- 238000004519 manufacturing process Methods 0.000 title claims description 6
- 238000000034 method Methods 0.000 claims description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 24
- -1 aryl ester epoxide Chemical class 0.000 claims description 24
- 238000010992 reflux Methods 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 150000001412 amines Chemical class 0.000 claims description 12
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 5
- 150000002430 hydrocarbons Chemical group 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 4
- 239000005977 Ethylene Chemical group 0.000 claims 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 4
- UJUKHOATWVVDER-UHFFFAOYSA-N 1-amino-1-phenoxypropan-1-ol Chemical compound CCC(N)(O)OC1=CC=CC=C1 UJUKHOATWVVDER-UHFFFAOYSA-N 0.000 claims 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 2
- 239000000174 gluconic acid Substances 0.000 claims 2
- 235000012208 gluconic acid Nutrition 0.000 claims 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 235000006408 oxalic acid Nutrition 0.000 claims 2
- 235000011007 phosphoric acid Nutrition 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 238000000921 elemental analysis Methods 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 238000001802 infusion Methods 0.000 description 19
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 17
- 238000012360 testing method Methods 0.000 description 17
- 239000000047 product Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000012429 reaction media Substances 0.000 description 12
- 239000002876 beta blocker Substances 0.000 description 11
- 210000002216 heart Anatomy 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 229940097320 beta blocking agent Drugs 0.000 description 10
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 229940039009 isoproterenol Drugs 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 230000000747 cardiac effect Effects 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- FQYUMYWMJTYZTK-UHFFFAOYSA-N Phenyl glycidyl ether Chemical compound C1OC1COC1=CC=CC=C1 FQYUMYWMJTYZTK-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 150000002148 esters Chemical group 0.000 description 5
- 208000019622 heart disease Diseases 0.000 description 5
- 210000003437 trachea Anatomy 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000000538 analytical sample Substances 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
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- FQTIYMRSUOADDK-UHFFFAOYSA-N ethyl 3-bromopropanoate Chemical compound CCOC(=O)CCBr FQTIYMRSUOADDK-UHFFFAOYSA-N 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
- 241000700199 Cavia porcellus Species 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 230000001746 atrial effect Effects 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000002837 heart atrium Anatomy 0.000 description 3
- 238000002329 infrared spectrum Methods 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- BDCUIFGTTIEBLT-UHFFFAOYSA-N methyl 3-[4-(oxiran-2-ylmethoxy)phenyl]propanoate Chemical compound C1=CC(CCC(=O)OC)=CC=C1OCC1OC1 BDCUIFGTTIEBLT-UHFFFAOYSA-N 0.000 description 3
- 150000003891 oxalate salts Chemical class 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 2
- KFUSXMDYOPXKKT-UHFFFAOYSA-N 2-[(2-methylphenoxy)methyl]oxirane Chemical compound CC1=CC=CC=C1OCC1OC1 KFUSXMDYOPXKKT-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- GLFVNTDRBTZJIY-UHFFFAOYSA-N diethyl 2-aminopropanedioate;hydron;chloride Chemical compound Cl.CCOC(=O)C(N)C(=O)OCC GLFVNTDRBTZJIY-UHFFFAOYSA-N 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- PSLIMVZEAPALCD-UHFFFAOYSA-N ethanol;ethoxyethane Chemical compound CCO.CCOCC PSLIMVZEAPALCD-UHFFFAOYSA-N 0.000 description 2
- NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- CDNNMNLILHWPMH-UHFFFAOYSA-N methyl 2-(oxiran-2-ylmethoxy)benzoate Chemical compound COC(=O)C1=CC=CC=C1OCC1OC1 CDNNMNLILHWPMH-UHFFFAOYSA-N 0.000 description 2
- XRAMJHXWXCMGJM-UHFFFAOYSA-N methyl 3-(4-hydroxyphenyl)propionate Chemical compound COC(=O)CCC1=CC=C(O)C=C1 XRAMJHXWXCMGJM-UHFFFAOYSA-N 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- SNBDGFZQPKCZTO-UHFFFAOYSA-N propanedioic acid;hydrochloride Chemical compound Cl.OC(=O)CC(O)=O SNBDGFZQPKCZTO-UHFFFAOYSA-N 0.000 description 2
- YYFIGOPUHPDIBO-UHFFFAOYSA-N propanoic acid;hydrochloride Chemical compound Cl.CCC(O)=O YYFIGOPUHPDIBO-UHFFFAOYSA-N 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000001603 reducing effect Effects 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 230000002889 sympathetic effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- MDYOLVRUBBJPFM-UHFFFAOYSA-N tropolone Chemical compound OC1=CC=CC=CC1=O MDYOLVRUBBJPFM-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- RQRSZRNJLQQNGJ-UHFFFAOYSA-N 1-(2-hydroxy-3-phenoxypropyl)pyrrolidine-2,5-dione Chemical compound O=C1CCC(=O)N1CC(O)COC1=CC=CC=C1 RQRSZRNJLQQNGJ-UHFFFAOYSA-N 0.000 description 1
- QYYCPWLLBSSFBW-UHFFFAOYSA-N 2-(naphthalen-1-yloxymethyl)oxirane Chemical compound C=1C=CC2=CC=CC=C2C=1OCC1CO1 QYYCPWLLBSSFBW-UHFFFAOYSA-N 0.000 description 1
- QMWAQHTYWDAKBC-UHFFFAOYSA-N 2-[(3-chlorophenoxy)methyl]oxirane Chemical compound ClC1=CC=CC(OCC2OC2)=C1 QMWAQHTYWDAKBC-UHFFFAOYSA-N 0.000 description 1
- KSLSZOOZWRMSAP-UHFFFAOYSA-N 2-[(4-chlorophenoxy)methyl]oxirane Chemical compound C1=CC(Cl)=CC=C1OCC1OC1 KSLSZOOZWRMSAP-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 108060003345 Adrenergic Receptor Proteins 0.000 description 1
- 102000017910 Adrenergic receptor Human genes 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010013496 Disturbance in attention Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N Methyl salicylate Natural products COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229940067621 aminobutyrate Drugs 0.000 description 1
- 229940124277 aminobutyric acid Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- XKXHCNPAFAXVRZ-UHFFFAOYSA-N benzylazanium;chloride Chemical group [Cl-].[NH3+]CC1=CC=CC=C1 XKXHCNPAFAXVRZ-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000007883 bronchodilation Effects 0.000 description 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
- 229960004484 carbachol Drugs 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- RJCGNNHKSNIUAT-UHFFFAOYSA-N ethyl 3-aminopropanoate;hydron;chloride Chemical compound Cl.CCOC(=O)CCN RJCGNNHKSNIUAT-UHFFFAOYSA-N 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 210000004744 fore-foot Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- QPNAREOPWNRCEQ-UHFFFAOYSA-N methyl 3-[4-[3-[(3-ethoxy-3-oxopropyl)amino]-2-hydroxypropoxy]phenyl]propanoate;hydrochloride Chemical compound Cl.CCOC(=O)CCNCC(O)COC1=CC=C(CCC(=O)OC)C=C1 QPNAREOPWNRCEQ-UHFFFAOYSA-N 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- RLXDCJUIXHSXQD-UHFFFAOYSA-N oxalic acid;hydrate Chemical compound O.OC(=O)C(O)=O.OC(=O)C(O)=O RLXDCJUIXHSXQD-UHFFFAOYSA-N 0.000 description 1
- PFPYHYZFFJJQFD-UHFFFAOYSA-N oxalic anhydride Chemical compound O=C1OC1=O PFPYHYZFFJJQFD-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-M phloretate Chemical compound OC1=CC=C(CCC([O-])=O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-L tyrosinate(2-) Chemical compound [O-]C(=O)C(N)CC1=CC=C([O-])C=C1 OUYCCCASQSFEME-UHFFFAOYSA-L 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 210000001186 vagus nerve Anatomy 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/02—Formation of carboxyl groups in compounds containing amino groups, e.g. by oxidation of amino alcohols
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/38—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US21134080A | 1980-11-28 | 1980-11-28 | |
| US211340 | 1980-11-28 | ||
| PCT/US1981/001515 WO1982001870A1 (en) | 1980-11-28 | 1981-11-16 | Compounds and method for treatment or prophylaxis of cardiac disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57502124A JPS57502124A (OSRAM) | 1982-12-02 |
| JPH0617345B2 true JPH0617345B2 (ja) | 1994-03-09 |
Family
ID=22786520
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP56503727A Expired - Lifetime JPH0617345B2 (ja) | 1980-11-28 | 1981-11-16 | 化合物およびその製造方法 |
Country Status (13)
| Country | Link |
|---|---|
| EP (2) | EP0053434B1 (OSRAM) |
| JP (1) | JPH0617345B2 (OSRAM) |
| KR (1) | KR880001827B1 (OSRAM) |
| AU (1) | AU546152B2 (OSRAM) |
| CA (1) | CA1183148A (OSRAM) |
| DK (1) | DK152491C (OSRAM) |
| EG (1) | EG15685A (OSRAM) |
| GR (1) | GR76307B (OSRAM) |
| IL (1) | IL64346A (OSRAM) |
| NZ (1) | NZ198945A (OSRAM) |
| RO (1) | RO85556B (OSRAM) |
| WO (1) | WO1982001870A1 (OSRAM) |
| ZA (1) | ZA817931B (OSRAM) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0053434B1 (en) * | 1980-11-28 | 1986-08-27 | American Hospital Supply Corporation | Compounds and method for treatment or prophylaxis of cardiac disorders |
| US4455317A (en) * | 1981-06-23 | 1984-06-19 | American Hospital Supply Corporation | Method for treating glaucoma by the topical administration of selectively metabolized beta-blocking agents |
| US4472301A (en) * | 1982-05-27 | 1984-09-18 | Miles Laboratories, Inc. | Propranolol immunogen and antibodies |
| US4687873A (en) * | 1983-02-03 | 1987-08-18 | The Regents Of The University Of California | Derivatives of β-adrenergic antagonists |
| ATE39245T1 (de) * | 1983-02-03 | 1988-12-15 | Univ California | Beta-adrenergisch antagonistische verbindungen und derivate von beta-adrenergischen antagonisten. |
| DE3836987A1 (de) * | 1988-10-31 | 1990-05-23 | Goedecke Ag | 2-aminocarbonsaeuren und deren derivate, verfahren zu deren herstellung und deren verwendung als arzneimittel |
| DE19943635A1 (de) * | 1999-09-13 | 2001-03-15 | Bayer Ag | Neuartige Aminodicarbonsäurederivate mit pharmazeutischen Eigenschaften |
| CN115536537B (zh) * | 2022-09-21 | 2023-09-22 | 华中农业大学 | 普萘洛尔衍生物及其在抑制植物病原菌中的应用 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3793365A (en) * | 1969-04-30 | 1974-02-19 | Boehringer Mannheim Gmbh | Amino acid derivatives |
| US4006184A (en) * | 1973-04-17 | 1977-02-01 | Ciba-Geigy Corporation | 1- OR 2-[2-Hydroxy-3-amino-propoxy]-9,10-dihydro-9,10-ethano-anthracenes and their salts |
| US4014920A (en) * | 1972-06-08 | 1977-03-29 | Ciba-Geigy Corporation | N-cinnamylcarbamic acid esters |
| US4146638A (en) * | 1976-02-17 | 1979-03-27 | Boehringer Ingelheim Gmbh | N-(3-phenoxy-2-hydroxy-propyl)-n-(2-phenyl-2-hydroxy-ethyl)-amines |
| JPS5724334A (en) * | 1980-06-02 | 1982-02-08 | Haessle Ab | Novel substituted 3-phenoxy-1-alkoxycarbonyl alkylamino-propanol-2 compound |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4241177A (en) * | 1978-08-28 | 1980-12-23 | Syva Company | Propanolol antigen conjugates and antibodies |
| EP0053434B1 (en) * | 1980-11-28 | 1986-08-27 | American Hospital Supply Corporation | Compounds and method for treatment or prophylaxis of cardiac disorders |
-
1981
- 1981-10-29 EP EP81305128A patent/EP0053434B1/en not_active Expired
- 1981-11-11 NZ NZ198945A patent/NZ198945A/en unknown
- 1981-11-16 AU AU78920/81A patent/AU546152B2/en not_active Expired
- 1981-11-16 EP EP81903189A patent/EP0065963B1/en not_active Expired
- 1981-11-16 WO PCT/US1981/001515 patent/WO1982001870A1/en not_active Ceased
- 1981-11-16 ZA ZA817931A patent/ZA817931B/xx unknown
- 1981-11-16 RO RO108294A patent/RO85556B/ro unknown
- 1981-11-16 JP JP56503727A patent/JPH0617345B2/ja not_active Expired - Lifetime
- 1981-11-24 IL IL64346A patent/IL64346A/xx not_active IP Right Cessation
- 1981-11-26 GR GR66621A patent/GR76307B/el unknown
- 1981-11-26 CA CA000390968A patent/CA1183148A/en not_active Expired
- 1981-11-28 KR KR1019810004621A patent/KR880001827B1/ko not_active Expired
- 1981-11-28 EG EG695/81A patent/EG15685A/xx active
-
1982
- 1982-07-27 DK DK334982A patent/DK152491C/da active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3793365A (en) * | 1969-04-30 | 1974-02-19 | Boehringer Mannheim Gmbh | Amino acid derivatives |
| US4014920A (en) * | 1972-06-08 | 1977-03-29 | Ciba-Geigy Corporation | N-cinnamylcarbamic acid esters |
| US4006184A (en) * | 1973-04-17 | 1977-02-01 | Ciba-Geigy Corporation | 1- OR 2-[2-Hydroxy-3-amino-propoxy]-9,10-dihydro-9,10-ethano-anthracenes and their salts |
| US4146638A (en) * | 1976-02-17 | 1979-03-27 | Boehringer Ingelheim Gmbh | N-(3-phenoxy-2-hydroxy-propyl)-n-(2-phenyl-2-hydroxy-ethyl)-amines |
| JPS5724334A (en) * | 1980-06-02 | 1982-02-08 | Haessle Ab | Novel substituted 3-phenoxy-1-alkoxycarbonyl alkylamino-propanol-2 compound |
Also Published As
| Publication number | Publication date |
|---|---|
| DK152491B (da) | 1988-03-07 |
| EG15685A (en) | 1986-12-30 |
| IL64346A (en) | 1988-12-30 |
| EP0065963A4 (en) | 1983-04-25 |
| RO85556A (ro) | 1985-03-15 |
| WO1982001870A1 (en) | 1982-06-10 |
| EP0053434B1 (en) | 1986-08-27 |
| AU546152B2 (en) | 1985-08-15 |
| DK152491C (da) | 1988-07-25 |
| AU7892081A (en) | 1982-06-17 |
| NZ198945A (en) | 1985-09-13 |
| CA1183148A (en) | 1985-02-26 |
| EP0053434A1 (en) | 1982-06-09 |
| EP0065963A1 (en) | 1982-12-08 |
| JPS57502124A (OSRAM) | 1982-12-02 |
| EP0065963B1 (en) | 1986-01-29 |
| GR76307B (OSRAM) | 1984-08-04 |
| KR830007510A (ko) | 1983-10-21 |
| DK334982A (da) | 1982-07-27 |
| RO85556B (ro) | 1985-03-30 |
| ZA817931B (en) | 1983-03-30 |
| KR880001827B1 (ko) | 1988-09-20 |
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