EA003084B1 - Простые бисэфиры 1-окса- и 1-азанафталин-2-онов в качестве ингибиторов фосфоламбана - Google Patents

Простые бисэфиры 1-окса- и 1-азанафталин-2-онов в качестве ингибиторов фосфоламбана Download PDF

Info

Publication number: EA003084B1
Authority: EA; Eurasian Patent Office
Prior art keywords: alkyl; aryl; hydrogen; compound; product
Prior art date: 1997-09-24

Application number

EA200000352A

Other languages

English (en)

Russian (ru)

Other versions

EA200000352A1 (ru

Inventor

Ярмо Пюстюнен

Эйя Тиайнен

Кари Леннберг

Пентти Норе

Сеппо Пархи

Арто Карьялайнен

Хеймо Хайкала

Йоуко Левийоки

Original Assignee

Орион Корпорейшн

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.)

1997-09-24

Filing date

1998-09-24

Publication date

2002-12-26

1998-09-24 Application filed by Орион Корпорейшн filed Critical Орион Корпорейшн

2000-10-30 Publication of EA200000352A1 publication Critical patent/EA200000352A1/ru

2002-12-26 Publication of EA003084B1 publication Critical patent/EA003084B1/ru

Links

102000005681 phospholamban Human genes 0.000 title description 10
108010059929 phospholamban Proteins 0.000 title description 10
239000003112 inhibitor Substances 0.000 title description 5
WZCKOKPKQZIGNU-UHFFFAOYSA-N 1h-naphthalen-2-one Chemical class C1=CC=C2C=CC(=O)CC2=C1 WZCKOKPKQZIGNU-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 63
125000000217 alkyl group Chemical group 0.000 claims abstract description 43
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
239000001257 hydrogen Substances 0.000 claims abstract description 27
-1 6-hydroxypyridazinyl Chemical group 0.000 claims abstract description 25
150000002431 hydrogen Chemical group 0.000 claims abstract description 22
125000000041 C6-C10 aryl group Chemical group 0.000 claims abstract description 15
150000002148 esters Chemical class 0.000 claims abstract description 13
150000003839 salts Chemical class 0.000 claims abstract description 13
150000002367 halogens Chemical group 0.000 claims abstract description 12
238000000034 method Methods 0.000 claims abstract description 12
229910052736 halogen Inorganic materials 0.000 claims abstract description 11
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
125000002947 alkylene group Chemical group 0.000 claims abstract description 5
206010019280 Heart failures Diseases 0.000 claims abstract description 4
125000004104 aryloxy group Chemical group 0.000 claims abstract description 4
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 3
239000004480 active ingredient Substances 0.000 claims abstract description 3
125000001589 carboacyl group Chemical group 0.000 claims abstract description 3
125000004181 carboxyalkyl group Chemical group 0.000 claims abstract description 3
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims abstract description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 7
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 4
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims abstract 2
239000003937 drug carrier Substances 0.000 claims abstract 2
238000002360 preparation method Methods 0.000 claims description 23
125000003118 aryl group Chemical group 0.000 claims description 18
238000002474 experimental method Methods 0.000 claims description 16
BXVSAYBZSGIURM-UHFFFAOYSA-N 2-phenoxy-4h-1,3,2$l^{5}-benzodioxaphosphinine 2-oxide Chemical group O1CC2=CC=CC=C2OP1(=O)OC1=CC=CC=C1 BXVSAYBZSGIURM-UHFFFAOYSA-N 0.000 claims description 9
230000003680 myocardial damage Effects 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
210000004165 myocardium Anatomy 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 2
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
125000001188 haloalkyl group Chemical group 0.000 abstract 1
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
208000002089 myocardial stunning Diseases 0.000 abstract 1
239000008194 pharmaceutical composition Substances 0.000 abstract 1
230000002265 prevention Effects 0.000 abstract 1
239000000047 product Substances 0.000 description 95
238000005160 1H NMR spectroscopy Methods 0.000 description 57
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ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 32
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 32
238000002844 melting Methods 0.000 description 32
230000008018 melting Effects 0.000 description 32
239000000243 solution Substances 0.000 description 32
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XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
239000011575 calcium Substances 0.000 description 18
229910000027 potassium carbonate Inorganic materials 0.000 description 18
239000011541 reaction mixture Substances 0.000 description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
235000011181 potassium carbonates Nutrition 0.000 description 17
RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 16
235000019270 ammonium chloride Nutrition 0.000 description 16
238000005481 NMR spectroscopy Methods 0.000 description 15
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238000010521 absorption reaction Methods 0.000 description 12
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 12
230000000694 effects Effects 0.000 description 11
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
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210000002027 skeletal muscle Anatomy 0.000 description 9
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
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AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 8
239000007787 solid Substances 0.000 description 8
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OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 7
229910052791 calcium Inorganic materials 0.000 description 7
210000005240 left ventricle Anatomy 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
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 6
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
238000011161 development Methods 0.000 description 5
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 5
239000004816 latex Substances 0.000 description 5
229920000126 latex Polymers 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000006228 supernatant Substances 0.000 description 5
DVNOTHMAOBZNRF-UHFFFAOYSA-N 1,3-dibenzyl-5,7-dihydroxy-4-methylquinolin-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(O)=CC(O)=C2C(C)=C1CC1=CC=CC=C1 DVNOTHMAOBZNRF-UHFFFAOYSA-N 0.000 description 4
241000700199 Cavia porcellus Species 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
229930006000 Sucrose Natural products 0.000 description 4
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 4
230000000747 cardiac effect Effects 0.000 description 4
239000004615 ingredient Substances 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
229940098779 methanesulfonic acid Drugs 0.000 description 4
239000005720 sucrose Substances 0.000 description 4
230000035488 systolic blood pressure Effects 0.000 description 4
POSZUTFLHGNLHX-KSBRXOFISA-N tris maleate Chemical compound OCC(N)(CO)CO.OCC(N)(CO)CO.OC(=O)\C=C/C(O)=O POSZUTFLHGNLHX-KSBRXOFISA-N 0.000 description 4
239000008096 xylene Substances 0.000 description 4
WNRGWPVJGDABME-UHFFFAOYSA-N 3,5-Dimethoxyaniline Chemical compound COC1=CC(N)=CC(OC)=C1 WNRGWPVJGDABME-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
241000700198 Cavia Species 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
ZYGHJZDHTFUPRJ-UHFFFAOYSA-N benzo-alpha-pyrone Natural products C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
239000003814 drug Substances 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
235000019256 formaldehyde Nutrition 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
238000005259 measurement Methods 0.000 description 3
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
238000012360 testing method Methods 0.000 description 3
230000002861 ventricular Effects 0.000 description 3
QCBXSNFQJIQQLN-UHFFFAOYSA-N 1,3-dibenzyl-4-methyl-5,7-bis(2h-tetrazol-5-ylmethoxy)quinolin-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(OCC=3NN=NN=3)=CC(OCC=3NN=NN=3)=C2C(C)=C1CC1=CC=CC=C1 QCBXSNFQJIQQLN-UHFFFAOYSA-N 0.000 description 2
OMCIABGQFWQXCQ-UHFFFAOYSA-N 1-benzyl-3-[(2-fluorophenyl)methyl]-4-methyl-5,7-bis(2h-tetrazol-5-ylmethoxy)quinolin-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(OCC=3NN=NN=3)=CC(OCC=3NN=NN=3)=C2C(C)=C1CC1=CC=CC=C1F OMCIABGQFWQXCQ-UHFFFAOYSA-N 0.000 description 2
IKFGDZUSKRJCGO-UHFFFAOYSA-N 1-benzyl-4-methyl-3-(2-phenylethyl)-5,7-bis(2h-tetrazol-5-ylmethoxy)quinolin-2-one Chemical compound O=C1N(CC=2C=CC=CC=2)C2=CC(OCC=3NN=NN=3)=CC(OCC=3NN=NN=3)=C2C(C)=C1CCC1=CC=CC=C1 IKFGDZUSKRJCGO-UHFFFAOYSA-N 0.000 description 2
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UQXBDKCUDUINDD-UHFFFAOYSA-N 3-[(4-chlorophenyl)methyl]-4-methyl-5,7-bis(2h-tetrazol-5-ylmethoxy)chromen-2-one Chemical compound O=C1OC=2C=C(OCC=3NN=NN=3)C=C(OCC=3NN=NN=3)C=2C(C)=C1CC1=CC=C(Cl)C=C1 UQXBDKCUDUINDD-UHFFFAOYSA-N 0.000 description 2
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IVIBYQNWSVHUGZ-UHFFFAOYSA-N 4-methyl-3-(2-phenylethyl)-5,7-bis(2h-tetrazol-5-ylmethoxy)chromen-2-one Chemical compound O=C1OC=2C=C(OCC=3NN=NN=3)C=C(OCC=3NN=NN=3)C=2C(C)=C1CCC1=CC=CC=C1 IVIBYQNWSVHUGZ-UHFFFAOYSA-N 0.000 description 2
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230000003993 interaction Effects 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000004020 luminiscence type Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
QAXZWHGWYSJAEI-UHFFFAOYSA-N n,n-dimethylformamide;ethanol Chemical compound CCO.CN(C)C=O QAXZWHGWYSJAEI-UHFFFAOYSA-N 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000008188 pellet Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
235000011056 potassium acetate Nutrition 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000010410 reperfusion Effects 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
241000894007 species Species 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
JKUYRAMKJLMYLO-UHFFFAOYSA-N tert-butyl 3-oxobutanoate Chemical compound CC(=O)CC(=O)OC(C)(C)C JKUYRAMKJLMYLO-UHFFFAOYSA-N 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
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
238000009736 wetting Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
- 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
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
- C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
- C07D311/16—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 7
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

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

EA200000352A 1997-09-24 1998-09-24 Простые бисэфиры 1-окса- и 1-азанафталин-2-онов в качестве ингибиторов фосфоламбана EA003084B1 (ru)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US93711997A	1997-09-24	1997-09-24
US99015097A	1997-12-12	1997-12-12
US10411498A	1998-06-25	1998-06-25
PCT/FI1998/000755 WO1999015523A1 (fr)	1997-09-24	1998-09-24	Bisethers de 1-oxa, aza et thianaphtalene-2-one inhibiteurs du phospholambane

Publications (2)

Publication Number	Publication Date
EA200000352A1 EA200000352A1 (ru)	2000-10-30
EA003084B1 true EA003084B1 (ru)	2002-12-26

Family

ID=27379660

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
EA200000352A EA003084B1 (ru)	1997-09-24	1998-09-24	Простые бисэфиры 1-окса- и 1-азанафталин-2-онов в качестве ингибиторов фосфоламбана

Country Status (18)

Country	Link
EP (1)	EP1017691A1 (fr)
JP (1)	JP2003525838A (fr)
KR (1)	KR20010015607A (fr)
CN (1)	CN1143857C (fr)
AU (1)	AU735729B2 (fr)
BR (1)	BR9813216A (fr)
CA (1)	CA2304849A1 (fr)
EA (1)	EA003084B1 (fr)
EE (1)	EE04494B1 (fr)
HU (1)	HUP0003647A3 (fr)
ID (1)	ID24373A (fr)
IL (1)	IL134662A0 (fr)
NO (1)	NO20001569L (fr)
NZ (1)	NZ503044A (fr)
PL (1)	PL339493A1 (fr)
SK (1)	SK3902000A3 (fr)
TR (1)	TR200000764T2 (fr)
WO (1)	WO1999015523A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU2001278980A1 (en) *	2000-07-21	2002-02-05	Chugai Seiyaku Kabushiki Kaisha	Coumarin derivatives useful as tnfalpha inhibitors
EP1491541B1 (fr) *	2001-03-30	2007-01-24	Pfizer Products Inc.	Pyridazinones, inhibiteurs d'aldose reductase.
US7572910B2 (en)	2003-02-20	2009-08-11	Pfizer, Inc.	Pyridazinone aldose reductase inhibitors
FR2970964B1 (fr) *	2011-01-28	2013-12-13	Univ Claude Bernard Lyon	Nouveaux derives d'azacoumarines presentant une activite inhibitrice des pompes mdr

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2543945A1 (de) *	1975-10-02	1977-04-21	Troponwerke Gmbh & Co Kg	2-benzopyranonderivate, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel
GB8529362D0 (en) *	1985-11-28	1986-01-02	Pfizer Ltd	Quinolone cardiac stimulants
GB8630702D0 (en) *	1986-12-23	1987-02-04	Wellcome Found	Quinoline compound
US5053514A (en) *	1988-08-10	1991-10-01	Otsuka Pharmaceutical Company, Limited	Cardiotonics
CA2022236A1 (fr) *	1989-07-31	1991-02-01	Hiroaki Yanagisawa	Derives de coumarin, leur preparation et leur utilisation pour le traitement des troubles cerebrovasculaires
DE4337906A1 (de) *	1993-11-08	1995-05-11	Cassella Ag	Verwendung von Cumarinderivaten

1998
- 1998-09-24 EP EP98946482A patent/EP1017691A1/fr not_active Withdrawn
- 1998-09-24 TR TR2000/00764T patent/TR200000764T2/xx unknown
- 1998-09-24 EE EEP200000179A patent/EE04494B1/xx not_active IP Right Cessation
- 1998-09-24 HU HU0003647A patent/HUP0003647A3/hu unknown
- 1998-09-24 IL IL13466298A patent/IL134662A0/xx unknown
- 1998-09-24 SK SK390-2000A patent/SK3902000A3/sk unknown
- 1998-09-24 JP JP2000512828A patent/JP2003525838A/ja active Pending
- 1998-09-24 BR BR9813216-4A patent/BR9813216A/pt not_active IP Right Cessation
- 1998-09-24 WO PCT/FI1998/000755 patent/WO1999015523A1/fr not_active Ceased
- 1998-09-24 ID IDW20000564A patent/ID24373A/id unknown
- 1998-09-24 CA CA002304849A patent/CA2304849A1/fr not_active Abandoned
- 1998-09-24 KR KR1020007003094A patent/KR20010015607A/ko not_active Ceased
- 1998-09-24 AU AU93508/98A patent/AU735729B2/en not_active Ceased
- 1998-09-24 EA EA200000352A patent/EA003084B1/ru not_active IP Right Cessation
- 1998-09-24 NZ NZ503044A patent/NZ503044A/en unknown
- 1998-09-24 PL PL98339493A patent/PL339493A1/xx unknown
- 1998-09-24 CN CNB98809438XA patent/CN1143857C/zh not_active Expired - Fee Related
2000
- 2000-03-24 NO NO20001569A patent/NO20001569L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
EP1017691A1 (fr)	2000-07-12
IL134662A0 (en)	2001-04-30
NO20001569D0 (no)	2000-03-24
BR9813216A (pt)	2000-08-29
CN1271357A (zh)	2000-10-25
AU735729B2 (en)	2001-07-12
HUP0003647A2 (hu)	2001-08-28
PL339493A1 (en)	2000-12-18
SK3902000A3 (en)	2000-12-11
EA200000352A1 (ru)	2000-10-30
EE200000179A (et)	2001-04-16
CA2304849A1 (fr)	1999-04-01
WO1999015523A1 (fr)	1999-04-01
JP2003525838A (ja)	2003-09-02
EE04494B1 (et)	2005-06-15
CN1143857C (zh)	2004-03-31
HUP0003647A3 (en)	2002-12-28
KR20010015607A (ko)	2001-02-26
NZ503044A (en)	2001-08-31
NO20001569L (no)	2000-03-24
ID24373A (id)	2000-07-13
AU9350898A (en)	1999-04-12
TR200000764T2 (tr)	2001-03-21

Legal Events

Date	Code	Title	Description
2007-06-29	MM4A	Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s)	Designated state(s): AM AZ BY KZ KG MD TJ TM RU

Publication	Publication Date	Title
US4725691A (en)	1988-02-16	2-[8-quinolinyl]-sulphinyl-1H-benzimidazole
RU2240998C2 (ru)	2004-11-27	Производные 3-замещенного 4-арилхинолин-2-она в качестве модуляторов калиевых каналов
US4452811A (en)	1984-06-05	Monohalogenated derivatives of 7-hydroxy-coumarin, pharmaceutical compositions containing the same and methods of using said compositions
RU2003134150A (ru)	2005-06-10	Замещенные карбоновыми кислотами оксазоловые производные в качестве ppar-альфа и гамма-активаторов при лечении диабета
AU2015314772B2 (en)	2020-02-27	Compositions and methods for treatment of prostate carcinoma
EP1039884B1 (fr)	2002-09-18	Methode de prevention et de traitement de la sideration myocardique
US6265421B1 (en)	2001-07-24	Phospholamban inhibitors and a method for increasing coronary flow
JP2001503373A (ja)	2001-03-13	血管系疾患の治療のための５ｈｔ▲下１ｂ▼レセプターアンタゴニストの使用
EA003084B1 (ru)	2002-12-26	Простые бисэфиры 1-окса- и 1-азанафталин-2-онов в качестве ингибиторов фосфоламбана
CN113264978B (zh)	2023-01-31	一种新型基于脂毒性的分子靶向抗肿瘤氮杂甾体衍生物及其制备方法和用途
EP1001774B1 (fr)	2004-09-15	Utilisation d'inhibiteurs de phospholamban pour augmenter le debit coronaire
JPH02184686A (ja)	1990-07-19	新規ベンゾピラニルピロリノン誘導体
MXPA00002954A (en)	2001-11-21	Bisethers of 1-oxa, aza and thianaphthalen-2-ones as phospholamban inhibitors
JPS5840959B2 (ja)	1983-09-08	アルド−ス還元酵素阻害剤スピロ−キノリルヒダントイン誘導体
JP3226174B2 (ja)	2001-11-05	３，４−ジヒドロ−２ｈ−１−ベンゾピラン類のヒドラジド誘導体類
CZ2000937A3 (cs)	2000-08-16	Bisethery 1-oxa, aza a thianaftalen-2-onu jako inhibitory fosfolambanu a farmaceutické prostředky
EP1450812A2 (fr)	2004-09-01	Utilisation de benzopyranones pour le traitement ou la prevention d'un cancer primitif du cerveau ou d'une metastase cerebrale
JP2000509726A (ja)	2000-08-02	糖尿病処置用のオキシランカルボン酸
EP1323419A1 (fr)	2003-07-02	Inhibiteurs de secretions de muqueuses des voies aeriennes
ZA200402765B (en)	2005-04-08	Use of benzopyranones for treating or preventing a primary brain cancer or a brain metastasis.