HRP20020816A2 - Pyridazinyl phenyl hydrazones useful against congestive heart failure - Google Patents

Pyridazinyl phenyl hydrazones useful against congestive heart failure Download PDF

Info

Publication number: HRP20020816A2
Authority: HR; Croatia
Prior art keywords: methyl; phenyl; hydrogen; pyridazin; hydroxy
Prior art date: 2000-03-13

Application number

Other languages

English (en)

Croatian (hr)

Inventor

Jarmo Pystynen

Aino Pippuri

Anne Luiro

Pentti Nore

Reijo Bockstroem

Kari Loennberg

Heimo Haikala

Jouko Levijoki

Petri Kaheinen

Juha Kaivola

Original Assignee

Orion Corp

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.)

2000-03-13

Filing date

2002-10-11

Publication date

2004-12-31

2002-10-11 Application filed by Orion Corp filed Critical Orion Corp

2004-12-31 Publication of HRP20020816A2 publication Critical patent/HRP20020816A2/hr

Links

-1 Pyridazinyl phenyl hydrazones Chemical class 0.000 title claims description 24
206010007559 Cardiac failure congestive Diseases 0.000 title 1
206010019280 Heart failures Diseases 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 65
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
238000000034 method Methods 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 28
239000001257 hydrogen Substances 0.000 claims description 28
150000002431 hydrogen Chemical class 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 17
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
150000003839 salts Chemical class 0.000 claims description 13
125000003118 aryl group Chemical group 0.000 claims description 11
125000003342 alkenyl group Chemical group 0.000 claims description 9
150000002148 esters Chemical class 0.000 claims description 9
125000003710 aryl alkyl group Chemical group 0.000 claims description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 7
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
125000002252 acyl group Chemical group 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
125000004181 carboxyalkyl group Chemical group 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
125000000041 C6-C10 aryl group Chemical group 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000004104 aryloxy group Chemical group 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
208000010125 myocardial infarction Diseases 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
125000004442 acylamino group Chemical group 0.000 claims description 3
229910052801 chlorine Chemical group 0.000 claims description 3
239000000460 chlorine Chemical group 0.000 claims description 3
125000001188 haloalkyl group Chemical group 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 2
239000000825 pharmaceutical preparation Substances 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 3
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 3
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 1
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims 1
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 132
238000005160 1H NMR spectroscopy Methods 0.000 description 66
238000002844 melting Methods 0.000 description 63
230000008018 melting Effects 0.000 description 63
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
239000000243 solution Substances 0.000 description 18
239000000203 mixture Substances 0.000 description 15
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
239000000047 product Substances 0.000 description 12
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 11
229910052791 calcium Inorganic materials 0.000 description 11
239000011575 calcium Substances 0.000 description 11
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 9
150000002429 hydrazines Chemical class 0.000 description 9
238000002474 experimental method Methods 0.000 description 8
239000000835 fiber Substances 0.000 description 7
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
102000002585 Contractile Proteins Human genes 0.000 description 6
108010068426 Contractile Proteins Proteins 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
210000004165 myocardium Anatomy 0.000 description 6
230000002861 ventricular Effects 0.000 description 6
230000000694 effects Effects 0.000 description 5
230000002349 favourable effect Effects 0.000 description 5
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 5
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
239000000872 buffer Substances 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
239000013078 crystal Substances 0.000 description 4
210000005240 left ventricle Anatomy 0.000 description 4
230000010412 perfusion Effects 0.000 description 4
230000035945 sensitivity Effects 0.000 description 4
239000002904 solvent Substances 0.000 description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
206010070834 Sensitisation Diseases 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
229910002092 carbon dioxide Inorganic materials 0.000 description 3
230000000747 cardiac effect Effects 0.000 description 3
229940079593 drug Drugs 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
239000004816 latex Substances 0.000 description 3
229920000126 latex Polymers 0.000 description 3
210000003540 papillary muscle Anatomy 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
238000010992 reflux Methods 0.000 description 3
230000008313 sensitization Effects 0.000 description 3
238000002604 ultrasonography Methods 0.000 description 3
HDJKGUBFDGUPFK-SSDOTTSWSA-N (4r)-3-(4-hydrazinylphenyl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound C[C@@H]1CC(=O)NN=C1C1=CC=C(NN)C=C1 HDJKGUBFDGUPFK-SSDOTTSWSA-N 0.000 description 2
SULYEHHGGXARJS-UHFFFAOYSA-N 2',4'-dihydroxyacetophenone Chemical compound CC(=O)C1=CC=C(O)C=C1O SULYEHHGGXARJS-UHFFFAOYSA-N 0.000 description 2
AQKWZDZQPZSATN-UHFFFAOYSA-N 3-(3-hydrazinylphenyl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=CC(NN)=C1 AQKWZDZQPZSATN-UHFFFAOYSA-N 0.000 description 2
HDJKGUBFDGUPFK-UHFFFAOYSA-N 3-(4-hydrazinylphenyl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=C(NN)C=C1 HDJKGUBFDGUPFK-UHFFFAOYSA-N 0.000 description 2
HFXZFCMCJBCLKJ-UHFFFAOYSA-N 3-[4-[2-[(3-ethyl-2,4-dihydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CCC1=C(O)C=CC(C=NNC=2C=CC(=CC=2)C=2C(CC(=O)NN=2)C)=C1O HFXZFCMCJBCLKJ-UHFFFAOYSA-N 0.000 description 2
CESZJTKLRJWMOD-UHFFFAOYSA-N 3-[4-[2-[1-(2,4-dihydroxyphenyl)ethylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=C(C)C1=CC=C(O)C=C1O CESZJTKLRJWMOD-UHFFFAOYSA-N 0.000 description 2
GZSNAXVXGFVPNU-UHFFFAOYSA-N 3-[4-[2-[1-(2,5-dihydroxyphenyl)ethylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=C(C)C1=CC(O)=CC=C1O GZSNAXVXGFVPNU-UHFFFAOYSA-N 0.000 description 2
OIJFPFSSXABMNR-UHFFFAOYSA-N 3-[4-[2-[bis(2,4-dihydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=C(C=1C(=CC(O)=CC=1)O)C1=CC=C(O)C=C1O OIJFPFSSXABMNR-UHFFFAOYSA-N 0.000 description 2
VBBCUFVTWROALH-UHFFFAOYSA-N 6-(4-hydrazinylphenyl)-2-methylpyridazin-3-one Chemical compound C1=CC(=O)N(C)N=C1C1=CC=C(NN)C=C1 VBBCUFVTWROALH-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
239000007993 MOPS buffer Substances 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
DRBBFCLWYRJSJZ-UHFFFAOYSA-N N-phosphocreatine Chemical compound OC(=O)CN(C)C(=N)NP(O)(O)=O DRBBFCLWYRJSJZ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
125000005236 alkanoylamino group Chemical group 0.000 description 2
125000005119 alkyl cycloalkyl group Chemical group 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
230000008859 change Effects 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
125000000753 cycloalkyl group Chemical group 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
125000004430 oxygen atom Chemical group O* 0.000 description 2
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
239000000523 sample Substances 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
239000000725 suspension Substances 0.000 description 2
150000003573 thiols Chemical class 0.000 description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
MWDICCJVJOMHSI-UHFFFAOYSA-N 2,4-dihydroxy-5-nitrobenzaldehyde Chemical compound OC1=CC(O)=C([N+]([O-])=O)C=C1C=O MWDICCJVJOMHSI-UHFFFAOYSA-N 0.000 description 1
JWYQQJDNADRNEL-UHFFFAOYSA-N 2-[c-[4-(4-methyl-6-oxo-4,5-dihydro-1h-pyridazin-3-yl)phenyl]carbonohydrazonoyl]benzoic acid Chemical compound CC1CC(=O)NN=C1C1=CC=C(C(=NN)C=2C(=CC=CC=2)C(O)=O)C=C1 JWYQQJDNADRNEL-UHFFFAOYSA-N 0.000 description 1
125000000094 2-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
SNHLRYZWIWHWFX-UHFFFAOYSA-N 3-(3-aminophenyl)-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C1=CC=CC(N)=C1 SNHLRYZWIWHWFX-UHFFFAOYSA-N 0.000 description 1
NWUOGOISBQCNKQ-UHFFFAOYSA-N 3-(4-aminophenyl)-4-methyl-1h-pyridazin-6-one Chemical compound CC1=CC(=O)NN=C1C1=CC=C(N)C=C1 NWUOGOISBQCNKQ-UHFFFAOYSA-N 0.000 description 1
FVTHDBGLGNPRCR-UHFFFAOYSA-N 3-(4-hydrazinylphenyl)-4-methyl-1h-pyridazin-6-one Chemical compound CC1=CC(=O)NN=C1C1=CC=C(NN)C=C1 FVTHDBGLGNPRCR-UHFFFAOYSA-N 0.000 description 1
TUGVJPGYSDTJAG-UHFFFAOYSA-N 3-[4-[2-[(2,3-dihydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC=CC(O)=C1O TUGVJPGYSDTJAG-UHFFFAOYSA-N 0.000 description 1
OJWAQBWUBKDRFC-UHFFFAOYSA-N 3-[4-[2-[(2,4-dichlorophenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC=C(Cl)C=C1Cl OJWAQBWUBKDRFC-UHFFFAOYSA-N 0.000 description 1
RGYYZELZQNFCDM-UHFFFAOYSA-N 3-[4-[2-[(2,4-dihydroxy-3-propylphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CCCC1=C(O)C=CC(C=NNC=2C=CC(=CC=2)C=2C(CC(=O)NN=2)C)=C1O RGYYZELZQNFCDM-UHFFFAOYSA-N 0.000 description 1
YQTPKDPKVJNQRL-UHFFFAOYSA-N 3-[4-[2-[(2,4-dihydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-ethyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CCC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC=C(O)C=C1O YQTPKDPKVJNQRL-UHFFFAOYSA-N 0.000 description 1
GULVWDKYICTUFG-UHFFFAOYSA-N 3-[4-[2-[(2,4-dihydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-1H-pyridazin-6-one Chemical compound CC1=CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC=C(O)C=C1O GULVWDKYICTUFG-UHFFFAOYSA-N 0.000 description 1
UUTFRQRDALQVDC-UHFFFAOYSA-N 3-[4-[2-[(2,4-dinitrophenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UUTFRQRDALQVDC-UHFFFAOYSA-N 0.000 description 1
YZVXQAINTJEDSP-UHFFFAOYSA-N 3-[4-[2-[(2,5-dihydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC(O)=CC=C1O YZVXQAINTJEDSP-UHFFFAOYSA-N 0.000 description 1
VQHMWDVBRXVIAY-UHFFFAOYSA-N 3-[4-[2-[(2,6-dinitrophenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=C([N+]([O-])=O)C=CC=C1[N+]([O-])=O VQHMWDVBRXVIAY-UHFFFAOYSA-N 0.000 description 1
OLDBHOFMKXDMAO-UHFFFAOYSA-N 3-[4-[2-[(2-hydroxy-3-methoxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound COC1=CC=CC(C=NNC=2C=CC(=CC=2)C=2C(CC(=O)NN=2)C)=C1O OLDBHOFMKXDMAO-UHFFFAOYSA-N 0.000 description 1
NDDNYERKAPSDBT-UHFFFAOYSA-N 3-[4-[2-[(2-hydroxy-5-nitrophenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC([N+]([O-])=O)=CC=C1O NDDNYERKAPSDBT-UHFFFAOYSA-N 0.000 description 1
JSNFRHBBODUWGL-UHFFFAOYSA-N 3-[4-[2-[(2-hydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC=CC=C1O JSNFRHBBODUWGL-UHFFFAOYSA-N 0.000 description 1
AEYIEDOXYQIXCL-UHFFFAOYSA-N 3-[4-[2-[(2-methoxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound COC1=CC=CC=C1C=NNC1=CC=C(C=2C(CC(=O)NN=2)C)C=C1 AEYIEDOXYQIXCL-UHFFFAOYSA-N 0.000 description 1
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ADJJXYKQXXZQKF-UHFFFAOYSA-N 3-[4-[2-[(3-acetyl-2,4-dihydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC=C(O)C(C(C)=O)=C1O ADJJXYKQXXZQKF-UHFFFAOYSA-N 0.000 description 1
QRJXGQFMBDQICY-UHFFFAOYSA-N 3-[4-[2-[(3-butyl-2,4-dihydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one Chemical compound CCCCC1=C(O)C=CC(C=NNC=2C=CC(=CC=2)C=2C(CC(=O)NN=2)C)=C1O QRJXGQFMBDQICY-UHFFFAOYSA-N 0.000 description 1
FSGJSUXXXAVURH-UHFFFAOYSA-N 3-[4-[2-[(3-hydroxyphenyl)methylidene]hydrazinyl]phenyl]-4-methyl-4,5-dihydro-1h-pyridazin-6-one Chemical compound CC1CC(=O)NN=C1C(C=C1)=CC=C1NN=CC1=CC=CC(O)=C1 FSGJSUXXXAVURH-UHFFFAOYSA-N 0.000 description 1
CBYGFAUAIISNTA-UHFFFAOYSA-N 3-[4-[2-[(4-hydroxy-3-methoxy-2-nitrophenyl)methylidene]hydrazinyl]phenyl]-4-methyl-1H-pyridazin-6-one Chemical compound COC1=C(O)C=CC(C=NNC=2C=CC(=CC=2)C=2C(=CC(=O)NN=2)C)=C1[N+]([O-])=O CBYGFAUAIISNTA-UHFFFAOYSA-N 0.000 description 1
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Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/04—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having less than three double bonds between ring members or between ring members and non-ring members

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Epidemiology (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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HRP20020816 2000-03-13 2002-10-11 Pyridazinyl phenyl hydrazones useful against congestive heart failure HRP20020816A2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
FI20000577A FI20000577A0 (fi)	2000-03-13	2000-03-13	Pyridatsinyylifenyylihydratsoneja
PCT/FI2001/000241 WO2001068611A1 (en)	2000-03-13	2001-03-12	Pyridazinyl phenyl hydrazones useful against congestive heart failure

Publications (1)

Publication Number	Publication Date
HRP20020816A2 true HRP20020816A2 (en)	2004-12-31

Family

ID=8557913

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HRP20020816 HRP20020816A2 (en)	2000-03-13	2002-10-11	Pyridazinyl phenyl hydrazones useful against congestive heart failure

Country Status (32)

Country	Link
US (1)	US6699868B2 (bg)
EP (1)	EP1265871B1 (bg)
JP (1)	JP2003527375A (bg)
KR (1)	KR20030001379A (bg)
CN (1)	CN1191241C (bg)
AR (1)	AR027644A1 (bg)
AT (1)	ATE317388T1 (bg)
AU (2)	AU4657701A (bg)
BG (1)	BG65859B1 (bg)
BR (1)	BR0109136A (bg)
CA (1)	CA2403188A1 (bg)
CZ (1)	CZ20022997A3 (bg)
DE (1)	DE60117131T2 (bg)
DK (1)	DK1265871T3 (bg)
EA (1)	EA005574B1 (bg)
EE (1)	EE200200520A (bg)
ES (1)	ES2256222T3 (bg)
FI (1)	FI20000577A0 (bg)
HK (1)	HK1052008A1 (bg)
HR (1)	HRP20020816A2 (bg)
HU (1)	HUP0300177A3 (bg)
IL (2)	IL151492A0 (bg)
MX (1)	MXPA02008997A (bg)
NO (1)	NO324172B1 (bg)
NZ (1)	NZ521162A (bg)
PL (1)	PL357107A1 (bg)
RS (1)	RS50439B (bg)
SI (1)	SI1265871T1 (bg)
SK (1)	SK287163B6 (bg)
UA (1)	UA74571C2 (bg)
WO (1)	WO2001068611A1 (bg)
ZA (1)	ZA200206917B (bg)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0015228D0 (en) *	2000-06-21	2000-08-16	Portela & Ca Sa	Substituted nitrated catechols, their use in the treatment of some central and peripheral nervous system disorders
JP4561698B2 (ja) *	2002-02-19	2010-10-13	小野薬品工業株式会社	縮合ピリダジン誘導体化合物およびその化合物を有効成分として含有する薬剤
EP1612204A4 (en) *	2003-03-31	2007-04-11	Daiichi Seiyaku Co	HYDRAZONE DERIVATIVE
GB0503962D0 (en)	2005-02-25	2005-04-06	Kudos Pharm Ltd	Compounds
WO2008013838A2 (en)	2006-07-25	2008-01-31	Cephalon, Inc.	Pyridizinone derivatives
US20100286150A1 (en)	2007-01-17	2010-11-11	Fia Westerholm	Levosimendan for use in treating chronic valvular disease
EP2762465B1 (en) *	2011-09-27	2018-01-10	Zeon Corporation	Intermediate for manufacture of polymerizable compound and process for manufacture thereof
ES2684776T3 (es) *	2013-01-18	2018-10-04	Bristol-Myers Squibb Company	Ftalazinonas e isoquinolinonas como inhibidores de ROCK
JPWO2019235569A1 (ja) *	2018-06-08	2021-07-08	日産化学株式会社	キナーゼ阻害剤

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3531658A1 (de)	1985-09-05	1987-03-12	Boehringer Mannheim Gmbh	Heterocyclisch substituierte indole, zwischenprodukte, verfahren zu ihrer herstellung und arzneimittel
GB8903130D0 (en) *	1989-02-11	1989-03-30	Orion Yhtymae Oy	Substituted pyridazinones
US5185332A (en) *	1989-02-11	1993-02-09	Orion-Yhtyma Oy	Thiadiazines and pharmaceutical compositions thereof as well as method of use
FI973804A (fi) *	1997-09-26	1999-03-27	Orion Yhtymae Oy	Levosimendaanin oraalisia koostumuksia

2000
- 2000-03-13 FI FI20000577A patent/FI20000577A0/fi unknown
2001
- 2001-03-12 BR BR0109136-0A patent/BR0109136A/pt not_active IP Right Cessation
- 2001-03-12 JP JP2001567705A patent/JP2003527375A/ja not_active Withdrawn
- 2001-03-12 US US10/221,348 patent/US6699868B2/en not_active Expired - Fee Related
- 2001-03-12 CZ CZ20022997A patent/CZ20022997A3/cs unknown
- 2001-03-12 AT AT01919489T patent/ATE317388T1/de not_active IP Right Cessation
- 2001-03-12 NZ NZ521162A patent/NZ521162A/en unknown
- 2001-03-12 RS YUP-685/02A patent/RS50439B/sr unknown
- 2001-03-12 IL IL15149201A patent/IL151492A0/xx active IP Right Grant
- 2001-03-12 WO PCT/FI2001/000241 patent/WO2001068611A1/en active IP Right Grant
- 2001-03-12 SK SK1288-2002A patent/SK287163B6/sk not_active IP Right Cessation
- 2001-03-12 SI SI200130518T patent/SI1265871T1/sl unknown
- 2001-03-12 EE EEP200200520A patent/EE200200520A/xx unknown
- 2001-03-12 MX MXPA02008997A patent/MXPA02008997A/es active IP Right Grant
- 2001-03-12 AR ARP010101149A patent/AR027644A1/es unknown
- 2001-03-12 AU AU4657701A patent/AU4657701A/xx active Pending
- 2001-03-12 KR KR1020027012066A patent/KR20030001379A/ko not_active Application Discontinuation
- 2001-03-12 EP EP01919489A patent/EP1265871B1/en not_active Expired - Lifetime
- 2001-03-12 PL PL01357107A patent/PL357107A1/xx not_active Application Discontinuation
- 2001-03-12 CA CA002403188A patent/CA2403188A1/en not_active Abandoned
- 2001-03-12 CN CNB018065309A patent/CN1191241C/zh not_active Expired - Fee Related
- 2001-03-12 HU HU0300177A patent/HUP0300177A3/hu unknown
- 2001-03-12 DE DE60117131T patent/DE60117131T2/de not_active Expired - Fee Related
- 2001-03-12 DK DK01919489T patent/DK1265871T3/da active
- 2001-03-12 EA EA200200973A patent/EA005574B1/ru not_active IP Right Cessation
- 2001-03-12 AU AU2001246577A patent/AU2001246577B2/en not_active Ceased
- 2001-03-12 ES ES01919489T patent/ES2256222T3/es not_active Expired - Lifetime
- 2001-12-03 UA UA2002108100A patent/UA74571C2/uk unknown
2002
- 2002-08-26 IL IL151492A patent/IL151492A/en not_active IP Right Cessation
- 2002-08-28 ZA ZA200206917A patent/ZA200206917B/en unknown
- 2002-09-05 NO NO20024247A patent/NO324172B1/no not_active IP Right Cessation
- 2002-10-08 BG BG107175A patent/BG65859B1/bg unknown
- 2002-10-11 HR HRP20020816 patent/HRP20020816A2/hr not_active Application Discontinuation
2003
- 2003-06-16 HK HK03104272A patent/HK1052008A1/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
JP2003527375A (ja)	2003-09-16
US6699868B2 (en)	2004-03-02
HUP0300177A2 (hu)	2003-07-28
ES2256222T3 (es)	2006-07-16
WO2001068611A1 (en)	2001-09-20
DK1265871T3 (da)	2006-06-06
EP1265871B1 (en)	2006-02-08
HUP0300177A3 (en)	2003-09-29
NO324172B1 (no)	2007-09-03
BR0109136A (pt)	2002-12-24
NO20024247D0 (no)	2002-09-05
YU68502A (sh)	2005-11-28
NO20024247L (no)	2002-10-25
FI20000577A0 (fi)	2000-03-13
ZA200206917B (en)	2003-07-30
NZ521162A (en)	2003-11-28
AU4657701A (en)	2001-09-24
PL357107A1 (en)	2004-07-12
KR20030001379A (ko)	2003-01-06
CZ20022997A3 (cs)	2003-04-16
CN1418196A (zh)	2003-05-14
SK12882002A3 (sk)	2003-06-03
CN1191241C (zh)	2005-03-02
AU2001246577B2 (en)	2006-08-31
BG65859B1 (bg)	2010-03-31
MXPA02008997A (es)	2003-04-25
SK287163B6 (sk)	2010-02-08
RS50439B (sr)	2009-12-31
SI1265871T1 (sl)	2006-06-30
CA2403188A1 (en)	2001-09-20
AR027644A1 (es)	2003-04-09
US20030158200A1 (en)	2003-08-21
EA200200973A1 (ru)	2003-02-27
IL151492A (en)	2007-09-20
ATE317388T1 (de)	2006-02-15
DE60117131T2 (de)	2006-10-26
DE60117131D1 (de)	2006-04-20
HK1052008A1 (en)	2003-08-29
IL151492A0 (en)	2003-04-10
UA74571C2 (en)	2006-01-16
BG107175A (bg)	2003-05-30
EA005574B1 (ru)	2005-04-28
EE200200520A (et)	2004-04-15
EP1265871A1 (en)	2002-12-18

Legal Events

Date	Code	Title
2004-12-31	A1OB	Publication of a patent application
2005-06-30	ARAI	Request for the grant of a patent on the basis of the submitted results of a substantive examination of a patent application
2011-03-02	ODBC	Application rejected

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US5679688A (en)	1997-10-21	Quinaldoyl-amine derivatives of oxo-and hydroxy-substituted hydrocarbons
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WO1992005162A1 (fr)	1992-04-02	Compose d'isoxazol, son sel pharmaceutiquement acceptable, et utilisation medicale dudit compose
JPH06508375A (ja)	1994-09-22	インダン−１，３−ジオンおよびインダン−１，２，３−トリオンの誘導体、それらの調製方法およびそれらの治療上の使用
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Sircar et al.	1987	Cardiotonic agents. 6. Synthesis and inotropic activity of 2, 4-dihydro-5-[4-(1H-imidazol-1-yl) phenyl]-3H-pyrazol-3-ones: ring-contracted analogs of imazodan (CI-914)
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