CA1166255A - 4,5-dihydro-6-(pyridinyl)-3(2h)-pyridazinones substituees en 2, preparation et utilisation comme agents cardiotoniques - Google Patents

4,5-dihydro-6-(pyridinyl)-3(2h)-pyridazinones substituees en 2, preparation et utilisation comme agents cardiotoniques

Info

Publication number: CA1166255A
Authority: CA; Canada
Prior art keywords: pyridinyl; methyl; acid; process according; dihydro
Prior art date: 1980-04-28
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

Application number

CA000376356A

Other languages

English (en)

Inventor

George Y. Lesher

William B. Dickinson

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

STWB Inc

Original Assignee

Sterling Drug Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1980-04-28

Filing date

1981-04-27

Publication date

1984-04-24

1981-04-27 Application filed by Sterling Drug Inc filed Critical Sterling Drug Inc

1984-04-24 Application granted granted Critical

1984-04-24 Publication of CA1166255A publication Critical patent/CA1166255A/fr

Status Expired legal-status Critical Current

Links

238000002360 preparation method Methods 0.000 title claims abstract description 12
-1 4,5-dihydro-2-substituted-6-(pyridinyl)-3(2h)- pyridazinones Chemical class 0.000 title claims description 44
230000003177 cardiotonic effect Effects 0.000 title abstract description 11
150000003839 salts Chemical class 0.000 claims abstract description 63
238000000034 method Methods 0.000 claims abstract description 50
150000001875 compounds Chemical class 0.000 claims abstract description 30
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
239000001257 hydrogen Substances 0.000 claims abstract description 26
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 25
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims abstract description 17
OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine Substances NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims abstract description 16
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims abstract description 8
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims abstract description 7
150000007522 mineralic acids Chemical class 0.000 claims abstract description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
238000006243 chemical reaction Methods 0.000 claims description 25
239000002253 acid Substances 0.000 claims description 20
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
238000010992 reflux Methods 0.000 claims description 6
150000004648 butanoic acid derivatives Chemical class 0.000 claims description 5
239000000126 substance Substances 0.000 claims description 5
UTISRGMYIPHHBR-UHFFFAOYSA-N 4-oxo-4-pyridin-4-ylbutanenitrile Chemical compound N#CCCC(=O)C1=CC=NC=C1 UTISRGMYIPHHBR-UHFFFAOYSA-N 0.000 claims description 4
WNDHJGIIUPAEBD-UHFFFAOYSA-N 5-methyl-3-pyridin-4-yl-4,5-dihydro-1h-pyridazin-6-one Chemical compound N1C(=O)C(C)CC(C=2C=CN=CC=2)=N1 WNDHJGIIUPAEBD-UHFFFAOYSA-N 0.000 claims description 4
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 3
APHMLGDTZFVBPX-UHFFFAOYSA-N 2-methyl-6-pyridin-4-yl-4,5-dihydropyridazin-3-one;hydrochloride Chemical compound Cl.C1CC(=O)N(C)N=C1C1=CC=NC=C1 APHMLGDTZFVBPX-UHFFFAOYSA-N 0.000 claims description 3
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
HTAWQGONZIWLRC-UHFFFAOYSA-N methylhydrazine;dihydrochloride Chemical compound Cl.Cl.CNN HTAWQGONZIWLRC-UHFFFAOYSA-N 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
239000000203 mixture Substances 0.000 abstract description 33
239000000543 intermediate Substances 0.000 abstract description 9
230000000747 cardiac effect Effects 0.000 abstract description 7
239000000496 cardiotonic agent Substances 0.000 abstract description 7
125000000217 alkyl group Chemical group 0.000 abstract description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 abstract 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
238000007792 addition Methods 0.000 description 27
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
239000002904 solvent Substances 0.000 description 16
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 12
239000000243 solution Substances 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 11
238000003756 stirring Methods 0.000 description 11
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
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210000003540 papillary muscle Anatomy 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
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239000012458 free base Substances 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
239000007787 solid Substances 0.000 description 7
FPZQRPTXDIFAJN-UHFFFAOYSA-N 2,4-dimethyl-6-pyridin-4-yl-4,5-dihydropyridazin-3-one Chemical compound CN1C(=O)C(C)CC(C=2C=CN=CC=2)=N1 FPZQRPTXDIFAJN-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000004310 lactic acid Substances 0.000 description 6
235000014655 lactic acid Nutrition 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000000376 reactant Substances 0.000 description 6
AAILEWXSEQLMNI-UHFFFAOYSA-N 1h-pyridazin-6-one Chemical compound OC1=CC=CN=N1 AAILEWXSEQLMNI-UHFFFAOYSA-N 0.000 description 5
IRWZLWUYVNDDIX-UHFFFAOYSA-N 2-methyl-6-pyridin-4-yl-4,5-dihydropyridazin-3-one Chemical compound C1CC(=O)N(C)N=C1C1=CC=NC=C1 IRWZLWUYVNDDIX-UHFFFAOYSA-N 0.000 description 5
NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 5
230000001746 atrial effect Effects 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
229940098779 methanesulfonic acid Drugs 0.000 description 5
KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
WBQLBWAOILVKJU-UHFFFAOYSA-N 2-methyl-4-oxo-4-pyridin-4-ylbutanenitrile Chemical compound N#CC(C)CC(=O)C1=CC=NC=C1 WBQLBWAOILVKJU-UHFFFAOYSA-N 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
WEZLANLGAPCPHL-UHFFFAOYSA-N methyl 4-cyano-2-methyl-4-morpholin-4-yl-4-pyridin-4-ylbutanoate Chemical compound C=1C=NC=CC=1C(C#N)(CC(C)C(=O)OC)N1CCOCC1 WEZLANLGAPCPHL-UHFFFAOYSA-N 0.000 description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 3
229940092714 benzenesulfonic acid Drugs 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
239000003795 chemical substances by application 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
239000013078 crystal Substances 0.000 description 3
210000002837 heart atrium Anatomy 0.000 description 3
239000012493 hydrazine sulfate Substances 0.000 description 3
229910000377 hydrazine sulfate Inorganic materials 0.000 description 3
ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 3
BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 3
239000008247 solid mixture Substances 0.000 description 3
238000010998 test method Methods 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
YWJGORHFDXGFTF-UHFFFAOYSA-N 2-methyl-6-pyridin-4-ylpyridazin-3-one Chemical compound C1=CC(=O)N(C)N=C1C1=CC=NC=C1 YWJGORHFDXGFTF-UHFFFAOYSA-N 0.000 description 2
FUSNOPLQVRUIIM-UHFFFAOYSA-N 4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-n-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide Chemical compound O=C1NC(C)(C)CN1C(N=C1N)=NC=C1C(=O)NC1=CC=CC(C(F)(F)F)=C1 FUSNOPLQVRUIIM-UHFFFAOYSA-N 0.000 description 2
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150000008044 alkali metal hydroxides Chemical class 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
239000002220 antihypertensive agent Substances 0.000 description 2
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KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 2
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125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
229940102838 methylmethacrylate Drugs 0.000 description 2
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HLEJRPYVIVBKRC-UHFFFAOYSA-N 2,4-dimethyl-6-pyridin-3-yl-4,5-dihydropyridazin-3-one Chemical compound CN1C(=O)C(C)CC(C=2C=NC=CC=2)=N1 HLEJRPYVIVBKRC-UHFFFAOYSA-N 0.000 description 1
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CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
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RSAJRAAFBGTDKP-UHFFFAOYSA-N 2-methyl-6-(5-methylpyridin-3-yl)-4,5-dihydropyridazin-3-one Chemical compound C1CC(=O)N(C)N=C1C1=CN=CC(C)=C1 RSAJRAAFBGTDKP-UHFFFAOYSA-N 0.000 description 1
PJJIWKUZDWXSAU-UHFFFAOYSA-N 2-methyl-6-(5-methylpyridin-3-yl)pyridazin-3-one Chemical compound CC1=CN=CC(C2=NN(C)C(=O)C=C2)=C1 PJJIWKUZDWXSAU-UHFFFAOYSA-N 0.000 description 1
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150000002500 ions Chemical class 0.000 description 1
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235000008390 olive oil Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000002895 organic esters Chemical class 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
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239000010452 phosphate Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
WFHJFIQWCRVFAZ-UHFFFAOYSA-N propyl 4-cyano-4-(3-ethylpyridin-4-yl)-2-methyl-4-morpholin-4-ylbutanoate Chemical compound C=1C=NC=C(CC)C=1C(C#N)(CC(C)C(=O)OCCC)N1CCOCC1 WFHJFIQWCRVFAZ-UHFFFAOYSA-N 0.000 description 1
229960004063 propylene glycol Drugs 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
ZHNFLHYOFXQIOW-LPYZJUEESA-N quinine sulfate dihydrate Chemical compound [H+].[H+].O.O.[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ZHNFLHYOFXQIOW-LPYZJUEESA-N 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
239000008279 sol Substances 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000012265 solid product Substances 0.000 description 1
230000003019 stabilising effect Effects 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
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239000008223 sterile water Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
239000000725 suspension Substances 0.000 description 1
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239000000454 talc Substances 0.000 description 1
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239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
ZFDIRQKJPRINOQ-UHFFFAOYSA-N transbutenic acid ethyl ester Natural products CCOC(=O)C=CC ZFDIRQKJPRINOQ-UHFFFAOYSA-N 0.000 description 1
238000013519 translation Methods 0.000 description 1
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239000000080 wetting agent Substances 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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/57—Nitriles
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Hospice & Palliative Care (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Heart & Thoracic Surgery (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA000376356A 1980-04-28 1981-04-27 4,5-dihydro-6-(pyridinyl)-3(2h)-pyridazinones substituees en 2, preparation et utilisation comme agents cardiotoniques Expired CA1166255A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US14456480A	1980-04-28	1980-04-28
US144,564		1980-04-28

Publications (1)

Publication Number	Publication Date
CA1166255A true CA1166255A (fr)	1984-04-24

Family

ID=22509146

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000376356A Expired CA1166255A (fr)	1980-04-28	1981-04-27	4,5-dihydro-6-(pyridinyl)-3(2h)-pyridazinones substituees en 2, preparation et utilisation comme agents cardiotoniques

Country Status (6)

Country	Link
JP (1)	JPS572284A (fr)
KR (1)	KR830005202A (fr)
AU (1)	AU6991781A (fr)
BE (1)	BE888567A (fr)
CA (1)	CA1166255A (fr)
ZA (1)	ZA812698B (fr)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DK0618204T3 (da) *	1991-11-29	1999-03-29	Zenyaku Kogyo Kk	Heterocyklisk forbindelse og et kardiotonikum, der indeholder dette som virksom bestanddel

1981
- 1981-04-24 ZA ZA00812698A patent/ZA812698B/xx unknown
- 1981-04-27 BE BE1/10210A patent/BE888567A/fr not_active IP Right Cessation
- 1981-04-27 CA CA000376356A patent/CA1166255A/fr not_active Expired
- 1981-04-27 KR KR1019810001436A patent/KR830005202A/ko not_active Ceased
- 1981-04-28 JP JP6510481A patent/JPS572284A/ja active Pending
- 1981-04-28 AU AU69917/81A patent/AU6991781A/en not_active Abandoned

Also Published As

Publication number	Publication date
ZA812698B (en)	1982-04-28
KR830005202A (ko)	1983-08-03
AU6991781A (en)	1981-11-05
BE888567A (fr)	1981-10-27
JPS572284A (en)	1982-01-07

Legal Events

Date	Code	Title	Description
2001-04-24	MKEX	Expiry

Publication	Publication Date	Title
EP0482208B1 (fr)	2000-07-19	Derive de pyridazinone
US4432979A (en)	1984-02-21	Pyridone compounds
CA1155848A (fr)	1983-10-25	6-(pyridinyl)-3(2h)-pyridazinones, leur preparation et leur utilisation comme cardiotoniques
JP4875623B2 (ja)	2012-02-15	壊死又はアポトーシスによって生じた組織損傷又は疾患の治療におけるポリ（ａｄｐ−リボース）ポリメラーゼ（ｐａｒｐ）阻害剤としての３，６−置換された５−アリールアミノ−１ｈ−ピリジン−２−オン誘導体及び関連化合物
US4465686A (en)	1984-08-14	5-(Hydroxy- and/or amino-phenyl)-6-(lower-alkyl)-2-(1H)-pyridinones, their cardiotonic use and preparation
US4599423A (en)	1986-07-08	Preparation of 5-(hydroxy- and/or aminophenyl-6-lower-alkyl)-2(1H)-pyridinones
US4504482A (en)	1985-03-12	[5(or 4)-(Pyridinyl)-2-pyrimidinyl]ureas and cardiotonic use thereof
CA1166255A (fr)	1984-04-24	4,5-dihydro-6-(pyridinyl)-3(2h)-pyridazinones substituees en 2, preparation et utilisation comme agents cardiotoniques
US4337253A (en)	1982-06-29	4,5-Dihydro-2-methyl-6-(4-pyridinyl)-3(2H)-pyridazinone and its use as a cardiotonic
CA1166253A (fr)	1984-04-24	4-amino-6-(pyridinyl)-3(2h)-pyridazinones, preparation et utilisation comme agents cardiotoniques
US4304775A (en)	1981-12-08	3-Hydrazino-6-(pyridinyl) pyridazines and cardiotonic use thereof
CA1131231A (fr)	1982-09-07	Selection de 3-acylamino-5-[4(ou 3)-pyridinyl]- 2(1h)-pyridinones, leur preparation et leur emploi comme cardiotoniques
JPS58154579A (ja)	1983-09-14	ピリミドン誘導体
US4590194A (en)	1986-05-20	3-[methyl or dimethyl)amino]-6-(pyridinyl)pyridazines and their cardiotonic use
CA1166254A (fr)	1984-04-24	6-(pyridinyl)-3(2h)-pyridazinones substituees en 4, preparation et utilisation comme agents cardiotoniques
US4463008A (en)	1984-07-31	2-Alkoxy-5-(pyridinyl)pyridines and cardiotonic use thereof
US4346221A (en)	1982-08-24	Preparation of 4-amino-6-(pyridinyl)-3(2H)-pyridazinones from 6-(pyridinyl)-3(2H)-pyridazinones
US4391811A (en)	1983-07-05	2-Amino-6-(pyridinyl)-3H-imidazo[4,5-b]pyridines and their cardiotonic use
GB2076807A (en)	1981-12-09	4,5-Dihydro-6(pyridinyl)-3(2H)- pyridazinones
US4354026A (en)	1982-10-12	3-Chloro-6-(pyridinyl)-pyridazines
US4338446A (en)	1982-07-06	Di-(lower-alkyl)hydroxy-[2-oxo-2-(pyridinyl)ethyl]-propanedioates
US4363911A (en)	1982-12-14	1,2-Dihydro-6-[2-(dimethylamino)ethenyl]-2-oxo-5-(pyridinyl) nicotinonitriles
CA1195981A (fr)	1985-10-29	(3-et/ou 4-)-(di ou monomethyl)-5-(pyridinyl ou hydroxyphenyl)-2(1h)-pyridinones; preparation et utilisation comme agents cardiotoniques
US4593028A (en)	1986-06-03	5-hetero aryl-substituted-2-pyridones useful as cardiotonic agents for treatment of congestive heart failure
US4362735A (en)	1982-12-07	3-[(3-Oxo-1-butenyl)amino]-5-(pyridinyl)-2(1H)-pyridinones and their cardiotonic use