FI60562C - Foerfarande foer framstaellning av antiarytmiska verkande bis-homoftalimidoalkylaminer - Google Patents
Foerfarande foer framstaellning av antiarytmiska verkande bis-homoftalimidoalkylaminer Download PDFInfo
- Publication number
- FI60562C FI60562C FI762027A FI762027A FI60562C FI 60562 C FI60562 C FI 60562C FI 762027 A FI762027 A FI 762027A FI 762027 A FI762027 A FI 762027A FI 60562 C FI60562 C FI 60562C
- Authority
- FI
- Finland
- Prior art keywords
- dimethyl
- general formula
- dioxo
- dihydro
- isoquinolyl
- Prior art date
Links
- -1 hydroxy, amino Chemical group 0.000 claims description 55
- 150000001875 compounds Chemical class 0.000 claims description 31
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 230000003288 anthiarrhythmic effect Effects 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 230000009467 reduction Effects 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- QGNQEODJYRGEJX-UHFFFAOYSA-N 4h-isoquinoline-1,3-dione Chemical compound C1=CC=C2C(=O)NC(=O)CC2=C1 QGNQEODJYRGEJX-UHFFFAOYSA-N 0.000 claims description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 239000003416 antiarrhythmic agent Substances 0.000 claims description 3
- ZHQLTKAVLJKSKR-UHFFFAOYSA-N homophthalic acid Chemical class OC(=O)CC1=CC=CC=C1C(O)=O ZHQLTKAVLJKSKR-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000002828 nitro derivatives Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 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
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 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
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims 2
- 230000021736 acetylation Effects 0.000 claims 1
- 238000006640 acetylation reaction Methods 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 78
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 64
- 238000002844 melting Methods 0.000 description 55
- 230000008018 melting Effects 0.000 description 55
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 41
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 30
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- OTBHHUPVCYLGQO-UHFFFAOYSA-N bis(3-aminopropyl)amine Chemical compound NCCCNCCCN OTBHHUPVCYLGQO-UHFFFAOYSA-N 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 238000012544 monitoring process Methods 0.000 description 8
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 239000001530 fumaric acid Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 230000000638 stimulation Effects 0.000 description 5
- BVBLBGFQYTUFKY-UHFFFAOYSA-N 2-[3-[3-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)propylamino]propyl]-4,4-dimethylisoquinoline-1,3-dione Chemical group O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCCNCCCN1C(=O)C(C)(C)C2=CC=CC=C2C1=O BVBLBGFQYTUFKY-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- MXHBBLXCPDKKFR-UHFFFAOYSA-N 2-[3-[3-(1,3-dioxo-4h-isoquinolin-2-yl)propyl-methylamino]propyl]-4h-isoquinoline-1,3-dione Chemical compound O=C1CC2=CC=CC=C2C(=O)N1CCCN(C)CCCN1C(=O)C2=CC=CC=C2CC1=O MXHBBLXCPDKKFR-UHFFFAOYSA-N 0.000 description 3
- LKTARUONHONULH-UHFFFAOYSA-N 2-[3-[3-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)propylamino]propyl]-4,4-dimethylisoquinoline-1,3-dione;hydrochloride Chemical compound Cl.O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCCNCCCN1C(=O)C(C)(C)C2=CC=CC=C2C1=O LKTARUONHONULH-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
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
- 229910021529 ammonia Inorganic materials 0.000 description 3
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 3
- WGYKZJWCGVVSQN-UHFFFAOYSA-N mono-n-propyl amine Natural products CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 208000003663 ventricular fibrillation Diseases 0.000 description 3
- CRKZBGHQEDTHHR-UHFFFAOYSA-N 2-[2-[2-aminoethyl(methyl)amino]ethyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound C1=CC=C2C(C)(C)C(=O)N(CCN(CCN)C)C(=O)C2=C1 CRKZBGHQEDTHHR-UHFFFAOYSA-N 0.000 description 2
- VFBNGYZXYZFQNI-UHFFFAOYSA-N 2-[4-[2-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)ethylamino]butyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCCCNCCN1C(=O)C(C)(C)C2=CC=CC=C2C1=O VFBNGYZXYZFQNI-UHFFFAOYSA-N 0.000 description 2
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- SGKUCINDEYNHGZ-UHFFFAOYSA-N 4,4-dimethyl-2-[2-(methylamino)ethyl]isoquinoline-1,3-dione Chemical compound C1=CC=C2C(C)(C)C(=O)N(CCNC)C(=O)C2=C1 SGKUCINDEYNHGZ-UHFFFAOYSA-N 0.000 description 2
- AKHSBAVQPIRVAG-UHFFFAOYSA-N 4h-isochromene-1,3-dione Chemical compound C1=CC=C2C(=O)OC(=O)CC2=C1 AKHSBAVQPIRVAG-UHFFFAOYSA-N 0.000 description 2
- UXLWDIKOHGKHGF-UHFFFAOYSA-N 7-methoxy-4,4-dimethyl-2-[2-(methylamino)ethyl]isoquinoline-1,3-dione Chemical compound CC1(C(N(C(C2=CC(=CC=C12)OC)=O)CCNC)=O)C UXLWDIKOHGKHGF-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 244000025254 Cannabis sativa Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 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
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 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
- 239000000460 chlorine Chemical group 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Chemical group 0.000 description 2
- 150000002431 hydrogen Chemical group 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
- 125000005956 isoquinolyl group Chemical group 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
- KMBPCQSCMCEPMU-UHFFFAOYSA-N n'-(3-aminopropyl)-n'-methylpropane-1,3-diamine Chemical compound NCCCN(C)CCCN KMBPCQSCMCEPMU-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 125000004344 phenylpropyl group Chemical group 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000006308 propyl amino group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-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
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 description 1
- 125000004809 1-methylpropylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- ZKNSMJVZQWSHQG-UHFFFAOYSA-N 2-(1-ethoxy-2-methyl-1-oxopropan-2-yl)-5-hydroxybenzoic acid Chemical compound CCOC(=O)C(C)(C)C1=CC=C(O)C=C1C(O)=O ZKNSMJVZQWSHQG-UHFFFAOYSA-N 0.000 description 1
- IXQBOKIDWKTRFI-UHFFFAOYSA-N 2-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)acetaldehyde Chemical compound C1=CC=C2C(C)(C)C(=O)N(CC=O)C(=O)C2=C1 IXQBOKIDWKTRFI-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
- SCIKKOUUZVUQQC-UHFFFAOYSA-N 2-[2-(3-aminopropylamino)propyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound C1=CC=C2C(C)(C)C(=O)N(CC(C)NCCCN)C(=O)C2=C1 SCIKKOUUZVUQQC-UHFFFAOYSA-N 0.000 description 1
- YPBGDMSDZBIFMD-UHFFFAOYSA-N 2-[2-[2-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)ethyl-methylamino]ethyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCN(C)CCN1C(=O)C(C)(C)C2=CC=CC=C2C1=O YPBGDMSDZBIFMD-UHFFFAOYSA-N 0.000 description 1
- UZULDHUGXJVSOF-UHFFFAOYSA-N 2-[2-[2-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)ethyl-methylamino]ethyl]-7-methoxy-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCN(C)CCN1C(=O)C2=CC(OC)=CC=C2C(C)(C)C1=O UZULDHUGXJVSOF-UHFFFAOYSA-N 0.000 description 1
- QTWONISGADLEHK-UHFFFAOYSA-N 2-[2-[2-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)ethylamino]ethyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCNCCN1C(=O)C(C)(C)C2=CC=CC=C2C1=O QTWONISGADLEHK-UHFFFAOYSA-N 0.000 description 1
- WQTIZUKOOQDYRE-UHFFFAOYSA-N 2-[2-[3-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)propyl-methylamino]ethyl]-7-methoxy-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCCN(C)CCN1C(=O)C2=CC(OC)=CC=C2C(C)(C)C1=O WQTIZUKOOQDYRE-UHFFFAOYSA-N 0.000 description 1
- QVGQENNWSVLBDR-UHFFFAOYSA-N 2-[3-(3-aminopropylamino)propyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound C1=CC=C2C(C)(C)C(=O)N(CCCNCCCN)C(=O)C2=C1 QVGQENNWSVLBDR-UHFFFAOYSA-N 0.000 description 1
- HBVQFNCAHZROBP-UHFFFAOYSA-N 2-[3-[1-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)propan-2-ylamino]propyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCCNC(C)CN1C(=O)C(C)(C)C2=CC=CC=C2C1=O HBVQFNCAHZROBP-UHFFFAOYSA-N 0.000 description 1
- KXQPGHKHZKKYLK-UHFFFAOYSA-N 2-[3-[2-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)ethyl-methylamino]propyl]-7-methoxy-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCN(C)CCCN1C(=O)C2=CC(OC)=CC=C2C(C)(C)C1=O KXQPGHKHZKKYLK-UHFFFAOYSA-N 0.000 description 1
- HDIHUIMWDNQZMH-UHFFFAOYSA-N 2-[3-[2-(4,4-dimethyl-1,3-dioxoisoquinolin-2-yl)ethylamino]propyl]-4,4-dimethylisoquinoline-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(C)(C)C(=O)N1CCCNCCN1C(=O)C(C)(C)C2=CC=CC=C2C1=O HDIHUIMWDNQZMH-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
- LOPRLJQBDURQJG-UHFFFAOYSA-N 2-[3-[3-(1,3-dioxo-4h-isoquinolin-2-yl)propyl-methylamino]propyl]-4h-isoquinoline-1,3-dione;hydrochloride Chemical compound Cl.O=C1CC2=CC=CC=C2C(=O)N1CCCN(C)CCCN1C(=O)C2=CC=CC=C2CC1=O LOPRLJQBDURQJG-UHFFFAOYSA-N 0.000 description 1
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- 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
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- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
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- 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
- 241000906446 Theraps Species 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
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- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
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- 238000004458 analytical method Methods 0.000 description 1
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- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- CKKXWJDFFQPBQL-SEPHDYHBSA-N azane;(e)-but-2-enedioic acid Chemical compound N.N.OC(=O)\C=C\C(O)=O CKKXWJDFFQPBQL-SEPHDYHBSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 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
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
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- 238000003776 cleavage reaction Methods 0.000 description 1
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- BTVWZWFKMIUSGS-UHFFFAOYSA-N dimethylethyleneglycol Natural products CC(C)(O)CO BTVWZWFKMIUSGS-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
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- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 210000002837 heart atrium Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 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
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 210000005240 left ventricle 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
- 239000000155 melt 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
- DTSDBGVDESRKKD-UHFFFAOYSA-N n'-(2-aminoethyl)propane-1,3-diamine Chemical compound NCCCNCCN DTSDBGVDESRKKD-UHFFFAOYSA-N 0.000 description 1
- VROUNQCTUDTEKW-UHFFFAOYSA-N n'-(3-aminopropyl)-n'-propylbutane-1,4-diamine Chemical compound NCCCN(CCC)CCCCN VROUNQCTUDTEKW-UHFFFAOYSA-N 0.000 description 1
- CSIOOUSJMRKIAQ-UHFFFAOYSA-N n'-(3-aminopropyl)-n'-propylpropane-1,3-diamine Chemical compound NCCCN(CCC)CCCN CSIOOUSJMRKIAQ-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
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- 150000007530 organic bases Chemical group 0.000 description 1
- 239000012074 organic phase Substances 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
- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
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- 238000007127 saponification reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission 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
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- ATHGHQPFGPMSJY-UHFFFAOYSA-N spermidine Chemical compound NCCCCNCCCN ATHGHQPFGPMSJY-UHFFFAOYSA-N 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
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- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
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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
Landscapes
- 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)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2533986 | 1975-07-30 | ||
| DE2533986A DE2533986C3 (de) | 1975-07-30 | 1975-07-30 | Bis-Homophthalimide, deren Salze, Verfahren zu deren Herstellung und ihre Verwendung als Antiarrhythmica |
| DE2622690 | 1976-05-21 | ||
| DE19762622690 DE2622690A1 (de) | 1976-05-21 | 1976-05-21 | Neue homophthalimide |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI762027A7 FI762027A7 (en, 2012) | 1977-01-31 |
| FI60562B FI60562B (fi) | 1981-10-30 |
| FI60562C true FI60562C (fi) | 1982-02-10 |
Family
ID=25769213
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI762027A FI60562C (fi) | 1975-07-30 | 1976-07-12 | Foerfarande foer framstaellning av antiarytmiska verkande bis-homoftalimidoalkylaminer |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US4031219A (en, 2012) |
| JP (1) | JPS6019296B2 (en, 2012) |
| AT (2) | AT352135B (en, 2012) |
| AU (1) | AU499065B2 (en, 2012) |
| CA (1) | CA1076116A (en, 2012) |
| CH (3) | CH622781A5 (en, 2012) |
| DK (1) | DK341576A (en, 2012) |
| ES (2) | ES449765A1 (en, 2012) |
| FI (1) | FI60562C (en, 2012) |
| FR (1) | FR2319358A1 (en, 2012) |
| GB (1) | GB1492349A (en, 2012) |
| GR (1) | GR60822B (en, 2012) |
| IE (1) | IE43931B1 (en, 2012) |
| IL (1) | IL50156A (en, 2012) |
| LU (1) | LU75485A1 (en, 2012) |
| MX (1) | MX3388E (en, 2012) |
| NL (1) | NL7608422A (en, 2012) |
| NO (1) | NO145950C (en, 2012) |
| NZ (1) | NZ181610A (en, 2012) |
| PT (1) | PT65422B (en, 2012) |
| SE (1) | SE432763B (en, 2012) |
| YU (1) | YU39771B (en, 2012) |
Families Citing this family (8)
| 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 |
| EP1844033B1 (de) * | 2005-01-28 | 2011-07-27 | Boehringer Ingelheim Pharma GmbH & Co. KG | Verfahren zur herstellung von isochroman und derivaten davon |
| WO2023288039A1 (en) * | 2021-07-16 | 2023-01-19 | Denali Therapeutics Inc. | Compounds, compositions and methods |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2271122A (en) * | 1938-12-27 | 1942-01-27 | Monsanto Chemicals | Process of vulcanizing rubber |
| SE368009B (en, 2012) * | 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 CH CH961776A patent/CH622781A5/de not_active IP Right Cessation
- 1976-07-27 GR GR51353A patent/GR60822B/el unknown
- 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 GB GB31725/76A patent/GB1492349A/en not_active Expired
- 1976-07-29 MX MX002105U patent/MX3388E/es unknown
- 1976-07-29 DK DK341576A patent/DK341576A/da not_active Application Discontinuation
- 1976-07-29 SE SE7608592A patent/SE432763B/xx not_active IP Right Cessation
- 1976-07-29 CA CA258,095A patent/CA1076116A/en not_active Expired
- 1976-07-29 NZ NZ181610A patent/NZ181610A/xx unknown
- 1976-07-29 NO NO762640A patent/NO145950C/no unknown
- 1976-07-29 NL NL7608422A patent/NL7608422A/xx not_active Application Discontinuation
- 1976-07-29 JP JP51090793A patent/JPS6019296B2/ja not_active Expired
- 1976-07-29 PT PT65422A patent/PT65422B/pt unknown
- 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
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: DR. KARL THOMAE GESELLSCHAFT MIT |