CH624104A5 - - Google Patents

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Info

Publication number: CH624104A5
Authority: CH; Switzerland
Prior art keywords: formula; dioxo; dimethyl; compound; dihydro
Prior art date: 1975-07-30

Application number

CH691980A

Other languages

German (de)

English (en)

Inventor

Eberhard Dr Kutter

Volkhard Dr Austel

Wolfgang Dr Eberlein

Joachim Dr Heider

Rudolf Prof Dr Kadatz

Walter Prof Dr Kobinger

Christian Dr Lillie

Original Assignee

Thomae Gmbh Dr K

Priority date (The priority date 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 date listed.)

1975-07-30

Filing date

1980-09-16

Publication date

1981-07-15

1975-07-30 Priority claimed from DE2533986A external-priority patent/DE2533986C3/de

1976-05-21 Priority claimed from DE19762622690 external-priority patent/DE2622690A1/de

1980-09-16 Application filed by Thomae Gmbh Dr K filed Critical Thomae Gmbh Dr K

1981-07-15 Publication of CH624104A5 publication Critical patent/CH624104A5/de

Links

-1 methoxyphenyl group Chemical group 0.000 claims description 44
150000001875 compounds Chemical class 0.000 claims description 17
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
125000004432 carbon atom Chemical group C* 0.000 claims description 12
238000000034 method Methods 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 6
125000002947 alkylene group Chemical group 0.000 claims description 6
238000006243 chemical reaction Methods 0.000 claims description 5
230000009467 reduction Effects 0.000 claims description 5
239000002904 solvent Substances 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
150000007522 mineralic acids Chemical class 0.000 claims description 4
150000007524 organic acids Chemical class 0.000 claims description 4
235000005985 organic acids Nutrition 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
QGNQEODJYRGEJX-UHFFFAOYSA-N 4h-isoquinoline-1,3-dione Chemical class C1=CC=C2C(=O)NC(=O)CC2=C1 QGNQEODJYRGEJX-UHFFFAOYSA-N 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
230000029936 alkylation Effects 0.000 claims description 3
238000005804 alkylation reaction Methods 0.000 claims description 3
239000003054 catalyst Substances 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
239000011737 fluorine Chemical group 0.000 claims description 3
150000002828 nitro derivatives Chemical class 0.000 claims description 3
238000002360 preparation method Methods 0.000 claims description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims description 2
150000001728 carbonyl compounds Chemical class 0.000 claims description 2
239000003638 chemical reducing agent Substances 0.000 claims description 2
239000000460 chlorine Chemical group 0.000 claims description 2
229910052801 chlorine Inorganic materials 0.000 claims description 2
238000005984 hydrogenation reaction Methods 0.000 claims description 2
238000006396 nitration reaction Methods 0.000 claims description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 27
238000002844 melting Methods 0.000 description 26
230000008018 melting Effects 0.000 description 26
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 21
150000001412 amines Chemical class 0.000 description 17
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 12
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 12
239000000126 substance Substances 0.000 description 11
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000000243 solution Substances 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
239000003480 eluent Substances 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
230000003288 anthiarrhythmic effect Effects 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
239000000203 mixture Substances 0.000 description 6
241001465754 Metazoa Species 0.000 description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
230000000638 stimulation Effects 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
229910002651 NO3 Inorganic materials 0.000 description 3
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 3
230000009471 action Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
230000037024 effective refractory period Effects 0.000 description 3
210000002837 heart atrium Anatomy 0.000 description 3
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
238000010992 reflux Methods 0.000 description 3
230000029058 respiratory gaseous exchange Effects 0.000 description 3
208000003663 ventricular fibrillation Diseases 0.000 description 3
FAGAKXYIRMPHRB-UHFFFAOYSA-N 2-[3-[3-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)propyl-methylamino]propyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCCN(C)CCCN1C(=O)C(C)(C)C2=CC=CC=C2C1=O FAGAKXYIRMPHRB-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
244000025254 Cannabis sativa Species 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
230000007059 acute toxicity Effects 0.000 description 2
231100000403 acute toxicity Toxicity 0.000 description 2
239000003416 antiarrhythmic agent Substances 0.000 description 2
CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
239000012230 colorless oil Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
230000008602 contraction Effects 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
230000007794 irritation Effects 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000012071 phase Substances 0.000 description 2
125000004344 phenylpropyl group Chemical group 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
238000000746 purification Methods 0.000 description 2
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
WNGKLCUTZIPPSF-SEPHDYHBSA-N (e)-but-2-enedioate;methylazanium Chemical compound [NH3+]C.[NH3+]C.[O-]C(=O)\C=C\C([O-])=O WNGKLCUTZIPPSF-SEPHDYHBSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 1
MNDIARAMWBIKFW-UHFFFAOYSA-N 1-bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 1
ZLZMKKRRVPHYPM-UHFFFAOYSA-N 2-(4-aminobutyl)-4,4-dimethylisoquinoline-1,3-dione Chemical compound C1=CC=C2C(C)(C)C(=O)N(CCCCN)C(=O)C2=C1 ZLZMKKRRVPHYPM-UHFFFAOYSA-N 0.000 description 1
WDLZZPSGAFFZTG-UHFFFAOYSA-N 2-[3-[3-(1,3-dioxo-4-propan-2-yl-4h-isoquinolin-2-yl)propyl-methylamino]propyl]-4-propan-2-yl-4h-isoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C(C)C)C(=O)N1CCCN(C)CCCN1C(=O)C2=CC=CC=C2C(C(C)C)C1=O WDLZZPSGAFFZTG-UHFFFAOYSA-N 0.000 description 1
PDCLANUEAUPPGZ-UHFFFAOYSA-N 2-[3-[3-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)propyl-ethylamino]propyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCCN(CC)CCCN1C(=O)C(C)(C)C2=CC=CC=C2C1=O PDCLANUEAUPPGZ-UHFFFAOYSA-N 0.000 description 1
NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
OVXJWSYBABKZMD-UHFFFAOYSA-N 2-chloro-1,1-diethoxyethane Chemical compound CCOC(CCl)OCC OVXJWSYBABKZMD-UHFFFAOYSA-N 0.000 description 1
ZXTHWIZHGLNEPG-UHFFFAOYSA-N 2-phenyl-4,5-dihydro-1,3-oxazole Chemical compound O1CCN=C1C1=CC=CC=C1 ZXTHWIZHGLNEPG-UHFFFAOYSA-N 0.000 description 1
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
XMZQWZJMTBCUFT-UHFFFAOYSA-N 3-bromopropylbenzene Chemical compound BrCCCC1=CC=CC=C1 XMZQWZJMTBCUFT-UHFFFAOYSA-N 0.000 description 1
VSRVOIDBBCKMTM-UHFFFAOYSA-N 4,4-dimethylisoquinoline-1,3-dione Chemical compound C1=CC=C2C(C)(C)C(=O)NC(=O)C2=C1 VSRVOIDBBCKMTM-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
125000004042 4-aminobutyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])N([H])[H] 0.000 description 1
IPLKGJHGWCVSOG-UHFFFAOYSA-N 4-chlorobutanoic acid Chemical compound OC(=O)CCCCl IPLKGJHGWCVSOG-UHFFFAOYSA-N 0.000 description 1
LBVIQTSIBYKVHH-UHFFFAOYSA-N 7-amino-2-[3-[3-(7-amino-4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)propyl-methylamino]propyl]-4,4-dimethylisoquinoline-1,3-dione;trihydrochloride Chemical compound Cl.Cl.Cl.O=C1C2=CC(N)=CC=C2C(C)(C)C(=O)N1CCCN(C)CCCN1C(=O)C(C)(C)C2=CC=C(N)C=C2C1=O LBVIQTSIBYKVHH-UHFFFAOYSA-N 0.000 description 1
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
239000001729 Ammonium fumarate Substances 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
241000700198 Cavia Species 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-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
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 1
208000001953 Hypotension Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
101100465000 Mus musculus Prag1 gene Proteins 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000013543 active substance Substances 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
230000002763 arrhythmic effect Effects 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
BUVHXKKULRZWER-UHFFFAOYSA-O bis[3-(4,4-dimethyl-7-nitro-1,3-dioxoisoquinolin-2-yl)propyl]-methylazanium;nitrate Chemical compound [O-][N+]([O-])=O.O=C1C2=CC([N+]([O-])=O)=CC=C2C(C)(C)C(=O)N1CCC[NH+](C)CCCN1C(=O)C(C)(C)C2=CC=C([N+]([O-])=O)C=C2C1=O BUVHXKKULRZWER-UHFFFAOYSA-O 0.000 description 1
KMPSNAGGSZNBHR-UHFFFAOYSA-O bis[3-(4,4-dimethyl-7-nitro-1,3-dioxoisoquinolin-2-yl)propyl]azanium;nitrate Chemical compound [O-][N+]([O-])=O.O=C1C2=CC([N+]([O-])=O)=CC=C2C(C)(C)C(=O)N1CCC[NH2+]CCCN1C(=O)C(C)(C)C2=CC=C([N+]([O-])=O)C=C2C1=O KMPSNAGGSZNBHR-UHFFFAOYSA-O 0.000 description 1
238000009835 boiling Methods 0.000 description 1
230000000059 bradycardiac effect Effects 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
210000003169 central nervous system Anatomy 0.000 description 1
210000000038 chest Anatomy 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
239000008298 dragée Substances 0.000 description 1
ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000011521 glass Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
125000001475 halogen functional group Chemical group 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
208000021822 hypotensive Diseases 0.000 description 1
230000001077 hypotensive effect Effects 0.000 description 1
230000000297 inotrophic effect Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
210000005246 left atrium Anatomy 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
230000009090 positive inotropic effect Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000036279 refractory period Effects 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000000391 smoking effect Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
- 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
- A61P9/06—Antiarrhythmics

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Cardiology (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)
Heart & Thoracic Surgery (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Steroid Compounds (AREA)

CH691980A 1975-07-30 1980-09-16 CH624104A5 (xx)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE2533986A DE2533986C3 (de)	1975-07-30	1975-07-30	Bis-Homophthalimide, deren Salze, Verfahren zu deren Herstellung und ihre Verwendung als Antiarrhythmica
DE19762622690 DE2622690A1 (de)	1976-05-21	1976-05-21	Neue homophthalimide

Publications (1)

Publication Number	Publication Date
CH624104A5 true CH624104A5 (xx)	1981-07-15

Family

ID=25769213

Family Applications (3)

Application Number	Title	Priority Date
CH961776A CH622781A5 (xx)	1975-07-30	1976-07-27
CH691880A CH624103A5 (xx)	1975-07-30	1980-09-16
CH691980A CH624104A5 (xx)	1975-07-30	1980-09-16

Family Applications Before (2)

Application Number	Title	Priority Date	Filing Date
CH961776A CH622781A5 (xx)	1975-07-30	1976-07-27
CH691880A CH624103A5 (xx)	1975-07-30	1980-09-16

Country Status (22)

Country	Link
US (1)	US4031219A (xx)
JP (1)	JPS6019296B2 (xx)
AT (2)	AT352135B (xx)
AU (1)	AU499065B2 (xx)
CA (1)	CA1076116A (xx)
CH (3)	CH622781A5 (xx)
DK (1)	DK341576A (xx)
ES (2)	ES449765A1 (xx)
FI (1)	FI60562C (xx)
FR (1)	FR2319358A1 (xx)
GB (1)	GB1492349A (xx)
GR (1)	GR60822B (xx)
IE (1)	IE43931B1 (xx)
IL (1)	IL50156A (xx)
LU (1)	LU75485A1 (xx)
MX (1)	MX3388E (xx)
NL (1)	NL7608422A (xx)
NO (1)	NO145950C (xx)
NZ (1)	NZ181610A (xx)
PT (1)	PT65422B (xx)
SE (1)	SE432763B (xx)
YU (1)	YU39771B (xx)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4315935A (en) *	1980-04-14	1982-02-16	Smithkline Corporation	N,N'-Bis[substituted-1,2,3,4-tetrahydroisoquinolinolyl]disulfonylimides and antiallergic compositions and method of use
US4317826A (en) *	1980-05-27	1982-03-02	Smithkline Corporation	N,N'-Bis[substituted-1,2,3,4 tetrahydroisoquinolyl]disulfonylimides and antiallergic compositions and method of use
US4321254A (en) *	1980-09-26	1982-03-23	Smithkline Corporation	Antiallergic imidodisulfamides
US4385047A (en) *	1981-01-05	1983-05-24	Smithkline Beckman Corporation	Antiallergic imidodisulfamides
DE3631013A1 (de) *	1986-09-12	1988-03-24	Thomae Gmbh Dr K	Neue naphthylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
DE3640641A1 (de) *	1986-11-28	1988-07-14	Thomae Gmbh Dr K	Neue heteroaromatische aminderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung
ATE517880T1 (de) *	2005-01-28	2011-08-15	Boehringer Ingelheim Pharma	Verfahren zur herstellung von isochroman und derivaten davon
US20240254132A1 (en) *	2021-07-16	2024-08-01	Denali Therapeutics Inc.	Compounds, compositions and methods

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2271122A (en) *	1938-12-27	1942-01-27	Monsanto Chemicals	Process of vulcanizing rubber
SE368009B (xx) *	1971-09-16	1974-06-17	Kabi Ab

1976
- 1976-07-07 AT AT495176A patent/AT352135B/de not_active IP Right Cessation
- 1976-07-10 ES ES449765A patent/ES449765A1/es not_active Expired
- 1976-07-12 FI FI762027A patent/FI60562C/fi not_active IP Right Cessation
- 1976-07-13 US US05/704,844 patent/US4031219A/en not_active Expired - Lifetime
- 1976-07-16 YU YU1758/76A patent/YU39771B/xx unknown
- 1976-07-27 GR GR51353A patent/GR60822B/el unknown
- 1976-07-27 CH CH961776A patent/CH622781A5/de not_active IP Right Cessation
- 1976-07-28 LU LU75485A patent/LU75485A1/xx unknown
- 1976-07-28 AU AU16334/76A patent/AU499065B2/en not_active Expired
- 1976-07-28 IL IL50156A patent/IL50156A/xx unknown
- 1976-07-29 MX MX002105U patent/MX3388E/es unknown
- 1976-07-29 NZ NZ181610A patent/NZ181610A/xx unknown
- 1976-07-29 GB GB31725/76A patent/GB1492349A/en not_active Expired
- 1976-07-29 PT PT65422A patent/PT65422B/pt unknown
- 1976-07-29 NO NO762640A patent/NO145950C/no unknown
- 1976-07-29 CA CA258,095A patent/CA1076116A/en not_active Expired
- 1976-07-29 DK DK341576A patent/DK341576A/da not_active Application Discontinuation
- 1976-07-29 JP JP51090793A patent/JPS6019296B2/ja not_active Expired
- 1976-07-29 NL NL7608422A patent/NL7608422A/xx not_active Application Discontinuation
- 1976-07-29 SE SE7608592A patent/SE432763B/xx not_active IP Right Cessation
- 1976-07-30 IE IE1705/76A patent/IE43931B1/xx unknown
- 1976-07-30 FR FR7623472A patent/FR2319358A1/fr active Granted
- 1976-12-29 ES ES454668A patent/ES454668A1/es not_active Expired
1978
- 1978-04-17 AT AT265578A patent/AT351542B/de not_active IP Right Cessation
1980
- 1980-09-16 CH CH691880A patent/CH624103A5/de not_active IP Right Cessation
- 1980-09-16 CH CH691980A patent/CH624104A5/de not_active IP Right Cessation

Also Published As

Publication number	Publication date
YU39771B (en)	1985-04-30
FR2319358B1 (xx)	1978-11-17
AT351542B (de)	1979-07-25
JPS6019296B2 (ja)	1985-05-15
FR2319358A1 (fr)	1977-02-25
US4031219A (en)	1977-06-21
LU75485A1 (xx)	1977-08-09
SE7608592L (sv)	1977-01-31
NL7608422A (nl)	1977-02-01
IE43931B1 (en)	1981-07-01
FI60562B (fi)	1981-10-30
GB1492349A (en)	1977-11-16
AU499065B2 (en)	1979-04-05
CH624103A5 (xx)	1981-07-15
CH622781A5 (xx)	1981-04-30
YU175876A (en)	1983-01-21
IE43931L (en)	1977-01-30
NO762640L (xx)	1977-02-01
NZ181610A (en)	1978-03-06
MX3388E (es)	1980-10-27
FI60562C (fi)	1982-02-10
DK341576A (da)	1977-01-31
NO145950C (no)	1982-06-30
SE432763B (sv)	1984-04-16
CA1076116A (en)	1980-04-22
IL50156A (en)	1979-09-30
ATA265578A (de)	1979-01-15
AT352135B (de)	1979-09-10
GR60822B (en)	1978-08-31
PT65422B (de)	1978-06-09
FI762027A (xx)	1977-01-31
NO145950B (no)	1982-03-22
PT65422A (de)	1976-08-01
AU1633476A (en)	1978-02-02
ATA495176A (de)	1979-02-15
JPS5217478A (en)	1977-02-09
ES449765A1 (es)	1977-08-16
IL50156A0 (en)	1976-09-30
ES454668A1 (es)	1977-12-01

Publication	Publication Date	Title
DE2558501C2 (xx)	1987-07-16
EP0026848A1 (de)	1981-04-15	Tetralinderivate, ihre Herstellung und Heilmittel, welche diese Verbindungen enthalten
DE1275069B (de)	1968-08-14	1-(3', 5'-Dihydroxyphenyl)-1-hydroxy-2-isopropylaminoalkane und Verfahren zu ihrer Herstellung
DE2461860C2 (xx)	1989-10-26
CH624104A5 (xx)	1981-07-15
CH545764A (xx)	1974-02-15
CH626047A5 (xx)	1981-10-30
DE2044172C3 (de)	1975-11-13	Pyrrolderivate, ein Verfahren zu ihrer Herstellung und Arzneimittel
DE2320058C2 (de)	1982-11-18	Propylendiaminderivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Präparate
CH640507A5 (en)	1984-01-13	Process for preparing novel 1-aryloxy-2-hydroxy-3-aminopropanes
DE2062055C3 (de)	1979-01-18	Propanolamin-Derivate, Verfahren zu ihrer Herstellung und sie enthaltende Arzneimittel
DE1195762B (de)	1965-07-01	Verfahren zur Herstellung von neuen Naphthalin-1, 4, 5, 8-tetracarbonsaeurediimiden
DD202158A5 (de)	1983-08-31	Verfahren zur herstellung von imidazolin-derivaten
AT359502B (de)	1980-11-10	Verfahren zur herstellung von neuen phenyl- aethylaminen und ihren physiologisch ver- traeglichen saeureadditionssalzen
DE2034588B2 (de)	1979-03-29	ej-Dimethoxy^-benzylisochinoline, Verfahren zu ihrer Herstellung und Arzneimittel
DE2227846A1 (de)	1973-01-04	Phenoxyessigsaeure-derivate und verfahren zu ihrer herstellung
DE2732906C2 (de)	1986-09-25	In 5-Stellung durch einen Aminoalkylrest substituierte Imidazo-isochinolin-dione, Verfahren zu ihrer Herstellung und Arzneimittel
DD149664A5 (de)	1981-07-22	Verfahren zur herstellung von 1,1'-biphenyl-2-yl-alkylamin-derivaten
DE1493522C (de)	1972-08-31	Verfahren zur Herstellung von Diphenyl propylaminderivaten
DE2345651A1 (de)	1974-03-28	Indolylalkylamine und verfahren zu ihrer herstellung
DE2140550C3 (de)	1977-12-29	2-Benzoylalkylbenzomorphane, Verfahren zu ihrer Herstellung und Arzneimittel
AT233556B (de)	1964-05-11	Verfahren zur Herstellung von neuen Phenylalkylaminen und ihren Säureadditionssalzen
DE1493928C (de)	1973-04-26	Basisch substituierte ß Tetrahydro furyl propionitnle und deren pharma kologisch nicht giftige Salze sowie Verfahren zu deren Herstellung
DE1593579C (xx)
DE2463468C2 (xx)	1989-12-28

Legal Events

Date	Code	Title	Description
1988-03-31	PL	Patent ceased
2024-10-31	PL	Patent ceased