FI74001C - Foerfarande foer framstaellning av ett terapeutiskt aktivt 5-alkyl-1,6-naftyridin-2(1h)-onderivat. - Google Patents
Foerfarande foer framstaellning av ett terapeutiskt aktivt 5-alkyl-1,6-naftyridin-2(1h)-onderivat. Download PDFInfo
- Publication number
- FI74001C FI74001C FI832739A FI832739A FI74001C FI 74001 C FI74001 C FI 74001C FI 832739 A FI832739 A FI 832739A FI 832739 A FI832739 A FI 832739A FI 74001 C FI74001 C FI 74001C
- Authority
- FI
- Finland
- Prior art keywords
- methyl
- compound
- give
- hydrogen
- naphthyridin
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 35
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 89
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 51
- 239000001257 hydrogen Substances 0.000 claims abstract description 50
- -1 hydroxy, amino, cyano, carbamyl Chemical group 0.000 claims abstract description 36
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 19
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 13
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 12
- 239000000203 mixture Substances 0.000 claims description 62
- 150000003839 salts Chemical class 0.000 claims description 46
- 239000002253 acid Chemical group 0.000 claims description 44
- OCCZJXAHSUCJSA-UHFFFAOYSA-N 5-methyl-1h-1,6-naphthyridin-2-one Chemical compound N1C(=O)C=CC2=C1C=CN=C2C OCCZJXAHSUCJSA-UHFFFAOYSA-N 0.000 claims description 18
- 238000010438 heat treatment Methods 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 125000002091 cationic group Chemical group 0.000 claims description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 10
- 239000012458 free base Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- PNKUSGQVOMIXLU-UHFFFAOYSA-N Formamidine Chemical compound NC=N PNKUSGQVOMIXLU-UHFFFAOYSA-N 0.000 claims description 5
- 229910021529 ammonia Inorganic materials 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 230000003301 hydrolyzing effect Effects 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 230000000911 decarboxylating effect Effects 0.000 claims description 3
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- CJXNPIYSWSPCAP-UHFFFAOYSA-N 4-methylidenecyclohexa-1,5-diene-1-sulfonic acid Chemical compound OS(=O)(=O)C1=CCC(=C)C=C1 CJXNPIYSWSPCAP-UHFFFAOYSA-N 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000009472 formulation Methods 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 10
- 239000000496 cardiotonic agent Substances 0.000 abstract description 3
- 230000003177 cardiotonic effect Effects 0.000 abstract description 3
- 150000005054 naphthyridines Chemical class 0.000 abstract 1
- 150000005299 pyridinones Chemical class 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 78
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
- 230000000875 corresponding effect Effects 0.000 description 28
- 239000002244 precipitate Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 23
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 22
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- 239000000706 filtrate Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 14
- 230000001746 atrial effect Effects 0.000 description 14
- 235000011054 acetic acid Nutrition 0.000 description 13
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 13
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 11
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 11
- 210000003205 muscle Anatomy 0.000 description 11
- 239000007787 solid Substances 0.000 description 9
- DFNCTXBIIIZMGQ-UHFFFAOYSA-N 3-amino-5-methyl-1h-1,6-naphthyridin-2-one Chemical compound N1C(=O)C(N)=CC2=C1C=CN=C2C DFNCTXBIIIZMGQ-UHFFFAOYSA-N 0.000 description 8
- HOSMSJUGKUGGDS-UHFFFAOYSA-N 5-acetyl-6-methyl-2-oxo-1h-pyridine-3-carboxylic acid Chemical compound CC(=O)C=1C=C(C(O)=O)C(=O)NC=1C HOSMSJUGKUGGDS-UHFFFAOYSA-N 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- ZQKMVHXJWJNEQG-UHFFFAOYSA-N 1h-1,6-naphthyridin-2-one Chemical compound C1=NC=CC2=NC(O)=CC=C21 ZQKMVHXJWJNEQG-UHFFFAOYSA-N 0.000 description 7
- 241000700199 Cavia porcellus Species 0.000 description 7
- 239000000908 ammonium hydroxide Substances 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000012452 mother liquor Substances 0.000 description 7
- JTLWXFRVOPSNEH-UHFFFAOYSA-N 5-acetyl-6-methyl-1h-pyridin-2-one Chemical compound CC(=O)C=1C=CC(=O)NC=1C JTLWXFRVOPSNEH-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 241000282326 Felis catus Species 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 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 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000000747 cardiac effect Effects 0.000 description 5
- 239000003974 emollient agent Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- GJDXWCJWQMZNGB-UHFFFAOYSA-N 5-acetyl-6-[2-(dimethylamino)ethenyl]-2-oxo-1h-pyridine-3-carbonitrile Chemical compound CN(C)C=CC=1NC(=O)C(C#N)=CC=1C(C)=O GJDXWCJWQMZNGB-UHFFFAOYSA-N 0.000 description 4
- MSXMPMNVVDJBHQ-UHFFFAOYSA-N 5-butanoyl-6-methyl-1h-pyridin-2-one Chemical compound CCCC(=O)C=1C=CC(=O)NC=1C MSXMPMNVVDJBHQ-UHFFFAOYSA-N 0.000 description 4
- GWCNLYWJTUWLAR-UHFFFAOYSA-N 6-methyl-5-propanoyl-1h-pyridin-2-one Chemical compound CCC(=O)C=1C=CC(=O)NC=1C GWCNLYWJTUWLAR-UHFFFAOYSA-N 0.000 description 4
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 4
- 239000005695 Ammonium acetate Substances 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 125000003282 alkyl amino group Chemical group 0.000 description 4
- 235000019257 ammonium acetate Nutrition 0.000 description 4
- 229940043376 ammonium acetate Drugs 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- YUWFSFDIGSMKNC-UHFFFAOYSA-N 3-hydroxy-5-methyl-1h-1,6-naphthyridin-2-one Chemical compound N1C(=O)C(O)=CC2=C1C=CN=C2C YUWFSFDIGSMKNC-UHFFFAOYSA-N 0.000 description 3
- TUHHRVVBKDNCHH-UHFFFAOYSA-N 3-methyl-1h-1,6-naphthyridin-2-one Chemical compound N1=CC=C2N=C(O)C(C)=CC2=C1 TUHHRVVBKDNCHH-UHFFFAOYSA-N 0.000 description 3
- FLJCJGRJHJFVGA-UHFFFAOYSA-N 5-acetyl-6-[2-(dimethylamino)ethenyl]-1h-pyridin-2-one Chemical compound CN(C)C=CC=1NC(=O)C=CC=1C(C)=O FLJCJGRJHJFVGA-UHFFFAOYSA-N 0.000 description 3
- IMEZBBSLGKURNZ-UHFFFAOYSA-N 5-acetyl-6-ethyl-1h-pyridin-2-one Chemical compound CCC=1NC(=O)C=CC=1C(C)=O IMEZBBSLGKURNZ-UHFFFAOYSA-N 0.000 description 3
- OHAQWEZPEZJQRK-UHFFFAOYSA-N 5-acetyl-6-methyl-2-oxo-1h-pyridine-3-carboxamide Chemical compound CC(=O)C=1C=C(C(N)=O)C(=O)NC=1C OHAQWEZPEZJQRK-UHFFFAOYSA-N 0.000 description 3
- QALHYZRDGFGSBJ-UHFFFAOYSA-N 5-butanoyl-6-[2-(dimethylamino)ethenyl]-1h-pyridin-2-one Chemical compound CCCC(=O)C=1C=CC(=O)NC=1C=CN(C)C QALHYZRDGFGSBJ-UHFFFAOYSA-N 0.000 description 3
- UQUSMSLLLGRRFW-UHFFFAOYSA-N 5-methyl-2-oxo-1h-1,6-naphthyridine-3-carbohydrazide Chemical compound N1C(=O)C(C(=O)NN)=CC2=C1C=CN=C2C UQUSMSLLLGRRFW-UHFFFAOYSA-N 0.000 description 3
- AYUPZBQOTRFJQK-UHFFFAOYSA-N 5-methyl-2-oxo-1h-1,6-naphthyridine-3-carbonitrile Chemical compound N1C(=O)C(C#N)=CC2=C1C=CN=C2C AYUPZBQOTRFJQK-UHFFFAOYSA-N 0.000 description 3
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- 150000007514 bases Chemical class 0.000 description 3
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- 125000006267 biphenyl group Chemical group 0.000 description 3
- 239000002178 crystalline material Substances 0.000 description 3
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- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 description 3
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- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
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- DOEUAIZWVJCJLK-UHFFFAOYSA-N 6-[2-(dimethylamino)ethenyl]-5-pentanoyl-1h-pyridin-2-one Chemical compound CCCCC(=O)C=1C=CC(=O)NC=1C=CN(C)C DOEUAIZWVJCJLK-UHFFFAOYSA-N 0.000 description 2
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- DCEXPDBKXFULHE-UHFFFAOYSA-N 6-methyl-5-pentanoyl-1h-pyridin-2-one Chemical compound CCCCC(=O)C=1C=CC(=O)NC=1C DCEXPDBKXFULHE-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
- C07D213/82—Amides; Imides in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C07D213/85—Nitriles in position 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US40445482 | 1982-08-02 | ||
| US06/404,454 US4415580A (en) | 1982-08-02 | 1982-08-02 | Certain 2-(1H)-pyridinones cardiotonic compositions containing same and method of using same |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI832739A0 FI832739A0 (fi) | 1983-07-28 |
| FI832739L FI832739L (fi) | 1984-02-03 |
| FI74001B FI74001B (fi) | 1987-08-31 |
| FI74001C true FI74001C (fi) | 1987-12-10 |
Family
ID=23599673
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI832739A FI74001C (fi) | 1982-08-02 | 1983-07-28 | Foerfarande foer framstaellning av ett terapeutiskt aktivt 5-alkyl-1,6-naftyridin-2(1h)-onderivat. |
Country Status (20)
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4595762A (en) * | 1982-08-25 | 1986-06-17 | Sterling Drug Inc. | 5-α-bromoalkanoyl-2-oxo-3-pyridinecarbonitriles |
| US4532247A (en) * | 1983-08-08 | 1985-07-30 | Sterling Drug Inc. | 5-(Hydroxyalkyl or alkanoyloxymethyl)-1,6-naphthyridin-2(1H)-one and cardiotonic use thereof |
| US4560691A (en) * | 1984-07-13 | 1985-12-24 | Sterling Drug Inc. | 5-(Phenyl)-1,6-naphthyridin-2(1H)-ones, their cardiotonic use and preparation |
| US4657919A (en) * | 1984-08-03 | 1987-04-14 | E. I. Du Pont De Nemours & Co. | Pyridone esters as inotropic agents |
| DE3431303A1 (de) * | 1984-08-25 | 1986-02-27 | Goedecke Ag | 1,6-naphthyridin-derivate, verfahren zu deren herstellung und deren verwendung |
| US4650806A (en) * | 1985-01-14 | 1987-03-17 | Sterling Drug Inc. | Cardiotonic 5-(heterylcarbonyl)-pyridones |
| US4567186A (en) * | 1985-01-14 | 1986-01-28 | Sterling Drug Inc. | 5-Heteryl-1,6-naphthyridin-2(1H)-ones, cardiotonic use thereof and intermediates therefor |
| US4697021A (en) * | 1985-01-28 | 1987-09-29 | Sterling Drug Inc. | 1,6-dihydro-6-oxo-3-pyridinecarbonitriles, intermediates for cardiotonic agents |
| NZ214837A (en) * | 1985-01-28 | 1988-10-28 | Sterling Drug Inc | 5-substituted 1,6 naphthyridin-2(1h)-ones |
| US4634772A (en) * | 1985-01-28 | 1987-01-06 | Sterling Drug Inc. | 2-[2-(di-lower-alkylamino)-1-propenyl]-6-methoxy-3-pyridinecarbonitriles, intermediates for cardiotonic agents |
| US4657915A (en) * | 1985-01-28 | 1987-04-14 | Sterling Drug Inc. | 1,6-naphthyridine-2(1H)-ones and their use as cardiotonic agents |
| US4716170A (en) * | 1985-01-28 | 1987-12-29 | Sterling Drug Inc. | 5-[1H-(5-membered-N-aromatic heteryl)-1-yl]-1,6-naphthyridin-2(1H)-ones and their cardiotonic use |
| ZA985870B (en) | 1997-07-15 | 1999-01-27 | Dainippon Pharmaceutical Co | 5-substituted-3-oxadiazolyl-1, 6-naphthyridin-2(1H)-one derivatives |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4072746A (en) * | 1975-10-14 | 1978-02-07 | Sterling Drug Inc. | 3-Amino-5-(pyridinyl)-2(1H)-pyridinones |
| US4363911A (en) * | 1981-09-03 | 1982-12-14 | Sterling Drug Inc. | 1,2-Dihydro-6-[2-(dimethylamino)ethenyl]-2-oxo-5-(pyridinyl) nicotinonitriles |
-
1982
- 1982-08-02 US US06/404,454 patent/US4415580A/en not_active Expired - Fee Related
-
1983
- 1983-07-20 NZ NZ204969A patent/NZ204969A/xx unknown
- 1983-07-25 IL IL69325A patent/IL69325A/xx unknown
- 1983-07-26 ZA ZA835446A patent/ZA835446B/xx unknown
- 1983-07-26 AU AU17291/83A patent/AU561679B2/en not_active Ceased
- 1983-07-27 PT PT77118A patent/PT77118B/pt not_active IP Right Cessation
- 1983-07-28 GR GR72074A patent/GR79370B/el unknown
- 1983-07-28 AT AT83107465T patent/ATE29883T1/de active
- 1983-07-28 EP EP83107465A patent/EP0101952B1/en not_active Expired
- 1983-07-28 FI FI832739A patent/FI74001C/fi not_active IP Right Cessation
- 1983-07-28 DE DE8383107465T patent/DE3373813D1/de not_active Expired
- 1983-07-28 EP EP86107627A patent/EP0204335A3/en not_active Ceased
- 1983-07-29 GT GT198303012A patent/GT198303012A/es unknown
- 1983-08-01 KR KR1019830003601A patent/KR870000959B1/ko not_active Expired
- 1983-08-01 DK DK350983A patent/DK350983A/da not_active Application Discontinuation
- 1983-08-01 ES ES524642A patent/ES8605515A1/es not_active Expired
- 1983-08-01 NO NO832784A patent/NO160077C/no unknown
- 1983-08-02 PH PH29344A patent/PH19871A/en unknown
- 1983-08-02 EG EG480/83A patent/EG16284A/xx active
- 1983-08-02 JP JP58141813A patent/JPS5944387A/ja active Pending
-
1984
- 1984-03-15 ES ES530632A patent/ES530632A0/es active Granted
-
1987
- 1987-09-29 MY MYPI87002238A patent/MY102475A/en unknown
-
1990
- 1990-07-25 DK DK176890A patent/DK176890A/da not_active IP Right Cessation
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: STERLING DRUG INC |