DE3324727C2 - - Google Patents
Info
- Publication number
- DE3324727C2 DE3324727C2 DE3324727A DE3324727A DE3324727C2 DE 3324727 C2 DE3324727 C2 DE 3324727C2 DE 3324727 A DE3324727 A DE 3324727A DE 3324727 A DE3324727 A DE 3324727A DE 3324727 C2 DE3324727 C2 DE 3324727C2
- Authority
- DE
- Germany
- Prior art keywords
- compound
- minutes
- calcium
- papaverine
- formula
- 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
Links
- -1 3,4-dimethoxyphenylethyl Chemical group 0.000 claims description 8
- 229940127291 Calcium channel antagonist Drugs 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 239000000480 calcium channel blocker Substances 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 150000007513 acids Chemical class 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
- 230000002490 cerebral effect Effects 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 description 43
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 30
- GYBONEHHSUABAO-UHFFFAOYSA-N bis[2-(3,4-dimethoxyphenyl)ethyl]-methylazanium;chloride Chemical compound [Cl-].C1=C(OC)C(OC)=CC=C1CC[NH+](C)CCC1=CC=C(OC)C(OC)=C1 GYBONEHHSUABAO-UHFFFAOYSA-N 0.000 description 25
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 18
- 229910001424 calcium ion Inorganic materials 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 241000700159 Rattus Species 0.000 description 16
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 15
- 230000000694 effects Effects 0.000 description 15
- 229960001789 papaverine Drugs 0.000 description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
- 230000005764 inhibitory process Effects 0.000 description 11
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 10
- 229960001597 nifedipine Drugs 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 229910001868 water Inorganic materials 0.000 description 10
- 239000000203 mixture Substances 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 7
- 239000011575 calcium Substances 0.000 description 7
- 229960001783 nicardipine Drugs 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 5
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 230000003185 calcium uptake Effects 0.000 description 5
- 210000003470 mitochondria Anatomy 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- 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 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 229940114079 arachidonic acid Drugs 0.000 description 4
- 235000021342 arachidonic acid Nutrition 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 210000004351 coronary vessel Anatomy 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 230000035508 accumulation Effects 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 210000000709 aorta Anatomy 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 238000011533 pre-incubation Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 210000003568 synaptosome Anatomy 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 208000003663 ventricular fibrillation Diseases 0.000 description 3
- 206010047302 ventricular tachycardia Diseases 0.000 description 3
- KDIKNBJFJOYFNY-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-[2-(3,4-dimethoxyphenyl)ethyl]acetamide Chemical compound C1=C(OC)C(OC)=CC=C1CCNC(=O)CC1=CC=C(OC)C(OC)=C1 KDIKNBJFJOYFNY-UHFFFAOYSA-N 0.000 description 2
- YSAXSWPDOFHENC-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-n-[2-(3,4-dimethoxyphenyl)ethyl]ethanamine Chemical compound C1=C(OC)C(OC)=CC=C1CCNCCC1=CC=C(OC)C(OC)=C1 YSAXSWPDOFHENC-UHFFFAOYSA-N 0.000 description 2
- QBJIMTPENIGDOG-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)acetyl chloride Chemical compound COC1=CC=C(CC(Cl)=O)C=C1OC QBJIMTPENIGDOG-UHFFFAOYSA-N 0.000 description 2
- ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 241000906446 Theraps Species 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 206010003119 arrhythmia Diseases 0.000 description 2
- 230000006793 arrhythmia Effects 0.000 description 2
- 210000005013 brain tissue Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 239000002027 dichloromethane extract Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 235000021588 free fatty acids Nutrition 0.000 description 2
- WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 description 2
- 210000003292 kidney cell Anatomy 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000002311 liver mitochondria Anatomy 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000011987 methylation Effects 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 2
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 101710169336 5'-deoxyadenosine deaminase Proteins 0.000 description 1
- 102000055025 Adenosine deaminases Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 206010048962 Brain oedema Diseases 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 238000012404 In vitro experiment Methods 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 241001442654 Percnon planissimum Species 0.000 description 1
- 241000287531 Psittacidae Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 230000008344 brain blood flow Effects 0.000 description 1
- 208000006752 brain edema Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000002213 calciumantagonistic effect Effects 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- MCTRZKAKODSRLQ-UHFFFAOYSA-N dimethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC([N+]([O-])=O)=C1 MCTRZKAKODSRLQ-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 230000000429 effect on vasoconstriction Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000007154 intracellular accumulation Effects 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- WRUGWIBCXHJTDG-UHFFFAOYSA-L magnesium sulfate heptahydrate Chemical compound O.O.O.O.O.O.O.[Mg+2].[O-]S([O-])(=O)=O WRUGWIBCXHJTDG-UHFFFAOYSA-L 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000036284 oxygen consumption Effects 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229940080817 rotenone Drugs 0.000 description 1
- JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- DDMGAAYEUNWXSI-XVSDJDOKSA-M sodium;(5z,8z,11z,14z)-icosa-5,8,11,14-tetraenoate Chemical compound [Na+].CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O DDMGAAYEUNWXSI-XVSDJDOKSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT22339/82A IT1218324B (it) | 1982-07-09 | 1982-07-09 | Composti ad attivita' calcio-antagonista,metodo per la loro preparazione e composizioni farmaceutiche |
| IT8320838A IT1206322B (it) | 1983-04-28 | 1983-04-28 | Composti ad attivita' bloccante del calcio a livello cardiaco e cerebrale, metodo per la loro preparazione e composizioni farmaceutiche. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3324727A1 DE3324727A1 (de) | 1984-01-12 |
| DE3324727C2 true DE3324727C2 (en, 2012) | 1988-09-22 |
Family
ID=26327676
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE3324727A Granted DE3324727A1 (de) | 1982-07-09 | 1983-07-08 | N-methyl-n-bis-(3,4-dimethoxyphenylaethyl)-amin, seine salze mit saeuren, arzneimittel und seine verwendung bei der behandlung von kardiovaskulaeren erkrankungen und zerebralen durchblutungsstoerungen |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4956389A (en, 2012) |
| CA (1) | CA1238858A (en, 2012) |
| CH (1) | CH654294A5 (en, 2012) |
| DE (1) | DE3324727A1 (en, 2012) |
| ES (1) | ES524353A0 (en, 2012) |
| FR (1) | FR2541113B1 (en, 2012) |
| GB (1) | GB2126213B (en, 2012) |
| NL (1) | NL185666C (en, 2012) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3630903A1 (de) * | 1986-09-11 | 1988-03-24 | Thomae Gmbh Dr K | Neue tetrahydronaphthalin- und indanderivate, verfahren zu deren herstellung sowie diese enthaltende arzneimittel |
| FR2646347B1 (fr) * | 1989-04-28 | 1991-08-23 | Roussel Uclaf | Nouveau derive d'hydroxyphenethylamine et ses sels, procede de preparation, application a titre de medicaments et utilisation comme outil pharmacologique specifique |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2006114A (en) * | 1931-04-27 | 1935-06-25 | Rosenmund Karl Wilhelm | Aliphatic-aromatic amine and process of making same |
| DE617647C (de) * | 1931-04-30 | 1935-08-23 | Karl Rosenmund Dr | Verfahren zur Darstellung von sekundaeren und tertiaeren Aminen der fettaromatischen Reihe |
| NL6813366A (en, 2012) * | 1967-11-13 | 1969-05-16 | ||
| US4181738A (en) * | 1976-11-30 | 1980-01-01 | Cornell Research Foundation, Inc. | Catecholamine derivatives, a process for their preparation and pharmaceutical compositions thereof |
-
1983
- 1983-07-05 CH CH3684/83A patent/CH654294A5/it not_active IP Right Cessation
- 1983-07-06 CA CA000431900A patent/CA1238858A/en not_active Expired
- 1983-07-07 GB GB08318467A patent/GB2126213B/en not_active Expired
- 1983-07-08 FR FR8311387A patent/FR2541113B1/fr not_active Expired
- 1983-07-08 DE DE3324727A patent/DE3324727A1/de active Granted
- 1983-07-08 NL NLAANVRAGE8302451,A patent/NL185666C/xx not_active IP Right Cessation
- 1983-07-08 ES ES524353A patent/ES524353A0/es active Granted
-
1985
- 1985-01-14 US US06/691,157 patent/US4956389A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| NL8302451A (nl) | 1984-02-01 |
| DE3324727A1 (de) | 1984-01-12 |
| NL185666C (nl) | 1990-06-18 |
| GB8318467D0 (en) | 1983-08-10 |
| GB2126213B (en) | 1986-01-29 |
| FR2541113B1 (fr) | 1986-11-14 |
| GB2126213A (en) | 1984-03-21 |
| ES8500885A1 (es) | 1984-11-16 |
| CH654294A5 (it) | 1986-02-14 |
| ES524353A0 (es) | 1984-11-16 |
| US4956389A (en) | 1990-09-11 |
| FR2541113A1 (fr) | 1984-08-24 |
| CA1238858A (en) | 1988-07-05 |
| NL185666B (nl) | 1990-01-16 |
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