DE3028272C2 - - Google Patents
Info
- Publication number
- DE3028272C2 DE3028272C2 DE3028272A DE3028272A DE3028272C2 DE 3028272 C2 DE3028272 C2 DE 3028272C2 DE 3028272 A DE3028272 A DE 3028272A DE 3028272 A DE3028272 A DE 3028272A DE 3028272 C2 DE3028272 C2 DE 3028272C2
- Authority
- DE
- Germany
- Prior art keywords
- dianhydro
- deoxy
- amino
- nitrate
- idit
- 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 - Fee Related
Links
- 229910002651 NO3 Inorganic materials 0.000 claims description 95
- 239000000203 mixture Substances 0.000 claims description 64
- 230000002829 reductive effect Effects 0.000 claims description 52
- -1 3,7-dimethylxanthine-1-yl Chemical group 0.000 claims description 42
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 31
- 229910017604 nitric acid Inorganic materials 0.000 claims description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 24
- 239000000047 product Substances 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 21
- KLDXJTOLSGUMSJ-JGWLITMVSA-N Isosorbide Chemical compound O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-JGWLITMVSA-N 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 19
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 17
- 125000006308 propyl amino group Chemical group 0.000 claims description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 150000003212 purines Chemical class 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 11
- 229960000583 acetic acid Drugs 0.000 claims description 11
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 11
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 11
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims description 10
- 239000004202 carbamide Substances 0.000 claims description 10
- 238000007098 aminolysis reaction Methods 0.000 claims description 9
- 229960002479 isosorbide Drugs 0.000 claims description 9
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 9
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims description 8
- 238000005915 ammonolysis reaction Methods 0.000 claims description 8
- 239000007795 chemical reaction product Substances 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 claims description 6
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 claims description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 229940075420 xanthine Drugs 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 5
- 238000009833 condensation Methods 0.000 claims description 5
- 230000005494 condensation Effects 0.000 claims description 5
- 230000000802 nitrating effect Effects 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 5
- FCZOVUJWOBSMSS-UHFFFAOYSA-N 5-[(6-aminopurin-9-yl)methyl]-5-methyl-3-methylideneoxolan-2-one Chemical compound C1=NC2=C(N)N=CN=C2N1CC1(C)CC(=C)C(=O)O1 FCZOVUJWOBSMSS-UHFFFAOYSA-N 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 4
- 239000004299 sodium benzoate Substances 0.000 claims description 4
- 235000010234 sodium benzoate Nutrition 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 150000003973 alkyl amines Chemical class 0.000 claims description 3
- 239000012362 glacial acetic acid Substances 0.000 claims description 3
- LRFVTYWOQMYALW-UHFFFAOYSA-N Xanthine Natural products O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 2
- 238000005903 acid hydrolysis reaction Methods 0.000 claims description 2
- 125000000848 adenin-9-yl group Chemical group [H]N([H])C1=C2N=C([H])N(*)C2=NC([H])=N1 0.000 claims description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 claims description 2
- 125000003282 alkyl amino group Chemical group 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000011261 inert gas Substances 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 239000004593 Epoxy Substances 0.000 claims 1
- 230000002378 acidificating effect Effects 0.000 claims 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
- 239000012050 conventional carrier Substances 0.000 claims 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 claims 1
- CBCIHIVRDWLAME-UHFFFAOYSA-N hexanitrodiphenylamine Chemical class [O-][N+](=O)C1=CC([N+](=O)[O-])=CC([N+]([O-])=O)=C1NC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O CBCIHIVRDWLAME-UHFFFAOYSA-N 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 188
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 181
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 118
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 99
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 77
- 239000000243 solution Substances 0.000 description 56
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 41
- 238000000921 elemental analysis Methods 0.000 description 38
- 238000001816 cooling Methods 0.000 description 30
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 30
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 30
- 239000012071 phase Substances 0.000 description 26
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 23
- 239000000706 filtrate Substances 0.000 description 22
- 229960000278 theophylline Drugs 0.000 description 22
- 239000002585 base Substances 0.000 description 21
- 238000001035 drying Methods 0.000 description 21
- 238000001704 evaporation Methods 0.000 description 21
- 238000003756 stirring Methods 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 19
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 18
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- 239000002026 chloroform extract Substances 0.000 description 15
- 230000008020 evaporation Effects 0.000 description 15
- 229960000201 isosorbide dinitrate Drugs 0.000 description 14
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 13
- 238000001953 recrystallisation Methods 0.000 description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 230000037396 body weight Effects 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- 229910000831 Steel Inorganic materials 0.000 description 10
- 239000010959 steel Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000000747 cardiac effect Effects 0.000 description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 9
- KLDXJTOLSGUMSJ-UNTFVMJOSA-N (3s,3ar,6s,6ar)-2,3,3a,5,6,6a-hexahydrofuro[3,2-b]furan-3,6-diol Chemical compound O[C@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-UNTFVMJOSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 239000000284 extract Substances 0.000 description 7
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 7
- 229960003827 isosorbide mononitrate Drugs 0.000 description 7
- 210000005240 left ventricle Anatomy 0.000 description 7
- 239000002244 precipitate Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 6
- 238000012512 characterization method Methods 0.000 description 6
- 230000032050 esterification Effects 0.000 description 6
- 238000005886 esterification reaction Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 239000012458 free base Substances 0.000 description 5
- 229940098779 methanesulfonic acid Drugs 0.000 description 5
- 239000012452 mother liquor Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- GCEJJEYAPRULFS-UHFFFAOYSA-N 1-(3-bromopropyl)-3,7-dimethylpurine-2,6-dione Chemical compound CN1C(=O)N(CCCBr)C(=O)C2=C1N=CN2C GCEJJEYAPRULFS-UHFFFAOYSA-N 0.000 description 4
- GPOZWEMBRIJYDP-UHFFFAOYSA-N 7-(3-bromopropyl)-1-methyl-3-(2-methylpropyl)purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N(CCCBr)C=N2 GPOZWEMBRIJYDP-UHFFFAOYSA-N 0.000 description 4
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical class NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 4
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 4
- LCQLHJZYVOQKHU-UHFFFAOYSA-N N-carbamoylglutamic acid Chemical compound NC(=O)NC(C(O)=O)CCC(O)=O LCQLHJZYVOQKHU-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 229960000643 adenine Drugs 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- OJYGBLRPYBAHRT-IPQSZEQASA-N chloralose Chemical compound O1[C@H](C(Cl)(Cl)Cl)O[C@@H]2[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]21 OJYGBLRPYBAHRT-IPQSZEQASA-N 0.000 description 4
- 229950009941 chloralose Drugs 0.000 description 4
- 230000007717 exclusion Effects 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 150000002823 nitrates Chemical class 0.000 description 4
- 230000002048 spasmolytic effect Effects 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 4
- 230000002861 ventricular Effects 0.000 description 4
- GHGVDQNEKGZLPE-UHFFFAOYSA-N 1-(3-hydroxypropyl)-3,7-dimethylpurine-2,6-dione Chemical compound CN1C(=O)N(CCCO)C(=O)C2=C1N=CN2C GHGVDQNEKGZLPE-UHFFFAOYSA-N 0.000 description 3
- NQHKAWBYOGTSOH-UHFFFAOYSA-N 7-(3-hydroxypropyl)-1-methyl-3-(2-methylpropyl)purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N(CCCO)C=N2 NQHKAWBYOGTSOH-UHFFFAOYSA-N 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 208000005392 Spasm Diseases 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 210000002376 aorta thoracic Anatomy 0.000 description 3
- 230000004872 arterial blood pressure Effects 0.000 description 3
- 210000001367 artery Anatomy 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 210000001147 pulmonary artery Anatomy 0.000 description 3
- 210000005245 right atrium Anatomy 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 229960004559 theobromine Drugs 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
- CQVKMVQRSNNAGO-UHFFFAOYSA-N 2-[4-formyl-3-methyl-n-(2-methylsulfonyloxyethyl)anilino]ethyl methanesulfonate Chemical compound CC1=CC(N(CCOS(C)(=O)=O)CCOS(C)(=O)=O)=CC=C1C=O CQVKMVQRSNNAGO-UHFFFAOYSA-N 0.000 description 2
- LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 description 2
- ZZWGXGHWFOTKNP-UHFFFAOYSA-N 7-(2-bromoethyl)-1,3-dimethylpurine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CCBr)C=N2 ZZWGXGHWFOTKNP-UHFFFAOYSA-N 0.000 description 2
- DZIAWYYZORIFPF-UHFFFAOYSA-N 7-(4-bromobutyl)-1,3-dimethylpurine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CCCCBr)C=N2 DZIAWYYZORIFPF-UHFFFAOYSA-N 0.000 description 2
- XWQMXSNGFXQZDR-UHFFFAOYSA-N 9-(2-bromoethyl)purin-6-amine Chemical compound NC1=NC=NC2=C1N=CN2CCBr XWQMXSNGFXQZDR-UHFFFAOYSA-N 0.000 description 2
- BBWPZFLWQLAOPI-UHFFFAOYSA-N 9-(3-bromopropyl)purin-6-amine Chemical compound NC1=NC=NC2=C1N=CN2CCCBr BBWPZFLWQLAOPI-UHFFFAOYSA-N 0.000 description 2
- KQCVQDGGEHOVFG-UHFFFAOYSA-N 9-(4-bromobutyl)purin-6-amine Chemical compound NC1=NC=NC2=C1N=CN2CCCCBr KQCVQDGGEHOVFG-UHFFFAOYSA-N 0.000 description 2
- BMPUISBYXIHCMO-UHFFFAOYSA-N 9-(6-bromohexyl)purin-6-amine Chemical compound NC1=NC=NC2=C1N=CN2CCCCCCBr BMPUISBYXIHCMO-UHFFFAOYSA-N 0.000 description 2
- 229930024421 Adenine Natural products 0.000 description 2
- 241000320529 Allobates femoralis Species 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical class OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/08—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 1 and 3, e.g. theophylline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
- C07D473/10—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3 with methyl radicals in positions 3 and 7, e.g. theobromine
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmacology & Pharmacy (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)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19803028272 DE3028272A1 (de) | 1980-07-25 | 1980-07-25 | Durch purinbasen substituierte alkylamino-desoxy-1.4;3.6-dianhydro-hexit-nitrate, verfahren zu ihrer herstellung und pharmazeutische zubereitung |
| AT81104475T ATE10498T1 (de) | 1980-07-25 | 1981-06-11 | Durch purinbasen substituierte alkylamino-desoxy1.4;3.6-dianhydro-hexit-nitrate, verfahren zu ihrer herstellung und pharmazeutische zubereitung. |
| EP81104475A EP0044927B1 (de) | 1980-07-25 | 1981-06-11 | Durch Purinbasen substituierte Alkylamino-desoxy-1.4;3.6-dianhydro-hexit-nitrate, Verfahren zu ihrer Herstellung und pharmazeutische Zubereitung |
| ES503485A ES503485A0 (es) | 1980-07-25 | 1981-06-29 | Procedimiento para la preparacion de nitratos de alquilami- nodesoxi-1.4,3.6-dianhidro-hexito sustituidos con bases pu- rinicas |
| CA000381347A CA1186687A (en) | 1980-07-25 | 1981-07-08 | Alkylaminodesoxy-1.4;3.6-dianhydrohexitol nitrates substituted by purine bases, processes for their preparation and pharmaceutical compositions |
| AR286084A AR231141A1 (es) | 1980-07-25 | 1981-07-14 | Procedimiento para obtener nitratos de alquilamino-desoxi-1.4;3.6-dianhidrohexito,sustituidos por bases purinicas |
| MX188314A MX157614A (es) | 1980-07-25 | 1981-07-15 | Procedimiento para preparar derivados de isohexido |
| US06/285,425 US4542137A (en) | 1980-07-25 | 1981-07-20 | Alkylaminodesoxy-1.4;3.6-dianhydrohexitol nitrates substituted by purine bases and pharmaceutical compositions |
| JP56116320A JPS5758692A (en) | 1980-07-25 | 1981-07-24 | Purine base-substituted alkylaminodesoxy- 1,4;3,6-dianhydrohexitol nitrate, manufacture and medicinal composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19803028272 DE3028272A1 (de) | 1980-07-25 | 1980-07-25 | Durch purinbasen substituierte alkylamino-desoxy-1.4;3.6-dianhydro-hexit-nitrate, verfahren zu ihrer herstellung und pharmazeutische zubereitung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3028272A1 DE3028272A1 (de) | 1982-02-25 |
| DE3028272C2 true DE3028272C2 (en, 2012) | 1990-09-13 |
Family
ID=6108125
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19803028272 Granted DE3028272A1 (de) | 1980-07-25 | 1980-07-25 | Durch purinbasen substituierte alkylamino-desoxy-1.4;3.6-dianhydro-hexit-nitrate, verfahren zu ihrer herstellung und pharmazeutische zubereitung |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US4542137A (en, 2012) |
| EP (1) | EP0044927B1 (en, 2012) |
| JP (1) | JPS5758692A (en, 2012) |
| AR (1) | AR231141A1 (en, 2012) |
| AT (1) | ATE10498T1 (en, 2012) |
| CA (1) | CA1186687A (en, 2012) |
| DE (1) | DE3028272A1 (en, 2012) |
| ES (1) | ES503485A0 (en, 2012) |
| MX (1) | MX157614A (en, 2012) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3028273A1 (de) * | 1980-07-25 | 1982-02-25 | Fa. Dr. Willmar Schwabe, 7500 Karlsruhe | Durch purinbasen substituierte 1.4;3.6-dianhydro-hexit-nitrate |
| DE3704604A1 (de) * | 1987-02-13 | 1988-08-25 | Mack Chem Pharm | Oximether von 2,6-dioxabicyclo(3.3.0)octanonen, herstellungsverfahren und anwendung als arzneimittel |
| CA2014520C (en) * | 1989-04-17 | 1996-07-16 | Fumio Suzuki | Hexitol derivatives |
| US5817662A (en) * | 1992-11-09 | 1998-10-06 | Cell Therapeutics, Inc. | Substituted amino alkyl compounds |
| US6103730A (en) * | 1994-03-24 | 2000-08-15 | Cell Therapeutics, Inc. | Amine substituted compounds |
| US5807861A (en) * | 1994-03-24 | 1998-09-15 | Cell Therapeutics, Inc. | Amine substituted xanthinyl compounds |
| US5801182A (en) * | 1994-03-24 | 1998-09-01 | Cell Therapeutics, Inc. | Amine substituted compounds |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2852507A (en) * | 1955-02-23 | 1958-09-16 | Eastman Kodak Co | Method of preparing powdered salt-free cellulose acetate-dicarboxylates |
| DE1100640B (de) * | 1956-09-25 | 1961-03-02 | Chemiewerk Homburg | Verfahren zur Herstellung von basisch substituierten Alkylxanthin-Derivaten |
| DE1221641B (de) * | 1962-03-30 | 1966-07-28 | Degussa | Verfahren zur Herstellung von basisch substituierten Theophyllinderivaten |
| DE1545634A1 (de) * | 1965-10-15 | 1969-08-07 | Boehringer Mannheim Gmbh | Verfahren zur Herstellung von Adenosin-Ketalen |
| DE1545635A1 (de) * | 1965-10-16 | 1969-08-07 | Boehringer Mannheim Gmbh | Verfahren zur Herstellung von Adenosin-Derivaten |
| AU465217B2 (en) * | 1971-04-29 | 1975-09-18 | American Home Products Corporation | Mononitrte esters of 1,4:3, 6-dianhydro-d-glucitol |
| US3886186A (en) * | 1971-04-29 | 1975-05-27 | American Home Prod | Mononitrate esters of 1,4:3,6-dianhydro-d-glucitol |
| US4000137A (en) * | 1975-06-10 | 1976-12-28 | American Home Products Corporation | Antitumor derivatives of periodate-oxidized nucleosides |
| US4087603A (en) * | 1976-09-27 | 1978-05-02 | Eli Lilly And Company | Antifungal antibiotics |
| US4065488A (en) * | 1977-02-24 | 1977-12-27 | American Home Products Corporation | Process for preparing 1,4:3,6-dianhydro-D-glucitol 2-nitrate |
| JPS55113786A (en) * | 1979-02-23 | 1980-09-02 | Toyo Jozo Co Ltd | Novel substance, nepranosin b or f and its preparation |
| DE3028288A1 (de) * | 1980-07-25 | 1982-02-25 | Fa. Dr. Willmar Schwabe, 7500 Karlsruhe | Gegebenenfalls n-substituierte aminodesoxy-1.4;3.6-dianhydro-hexit-derivate, verfahren zu ihrer herstellung und deren verwendung |
-
1980
- 1980-07-25 DE DE19803028272 patent/DE3028272A1/de active Granted
-
1981
- 1981-06-11 AT AT81104475T patent/ATE10498T1/de not_active IP Right Cessation
- 1981-06-11 EP EP81104475A patent/EP0044927B1/de not_active Expired
- 1981-06-29 ES ES503485A patent/ES503485A0/es active Granted
- 1981-07-08 CA CA000381347A patent/CA1186687A/en not_active Expired
- 1981-07-14 AR AR286084A patent/AR231141A1/es active
- 1981-07-15 MX MX188314A patent/MX157614A/es unknown
- 1981-07-20 US US06/285,425 patent/US4542137A/en not_active Expired - Fee Related
- 1981-07-24 JP JP56116320A patent/JPS5758692A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| EP0044927A1 (de) | 1982-02-03 |
| DE3028272A1 (de) | 1982-02-25 |
| US4542137A (en) | 1985-09-17 |
| EP0044927B1 (de) | 1984-11-28 |
| JPS6248674B2 (en, 2012) | 1987-10-15 |
| ATE10498T1 (de) | 1984-12-15 |
| AR231141A1 (es) | 1984-09-28 |
| ES8301239A1 (es) | 1982-11-16 |
| MX157614A (es) | 1988-12-06 |
| JPS5758692A (en) | 1982-04-08 |
| CA1186687A (en) | 1985-05-07 |
| ES503485A0 (es) | 1982-11-16 |
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Legal Events
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| OM8 | Search report available as to paragraph 43 lit. 1 sentence 1 patent law | ||
| 8110 | Request for examination paragraph 44 | ||
| 8127 | New person/name/address of the applicant |
Owner name: DR. WILLMAR SCHWABE GMBH & CO, 7500 KARLSRUHE, DE |
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| Q176 | The application caused the suspense of an application |
Ref document number: 3028288 Country of ref document: DE |
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