FI114916B - Förfarande för framställning av 2-aryl-substituerade-4-hydroxi-1,2,5,10-tetrahydropyridazino [4,5-b] kinolin-1,10-dionderivat, som är terapeutiskt användbara vid vård av iskemiska sjukdomar i hjärnan - Google Patents

Förfarande för framställning av 2-aryl-substituerade-4-hydroxi-1,2,5,10-tetrahydropyridazino [4,5-b] kinolin-1,10-dionderivat, som är terapeutiskt användbara vid vård av iskemiska sjukdomar i hjärnan Download PDF

Info

Publication number: FI114916B
Authority: FI; Finland
Prior art keywords: give; chloro; suspension; quinoline; compound
Prior art date: 1993-10-22

Application number

FI970907A

Other languages

English (en)

Finnish (fi)

Other versions

FI970907A0 (sv

FI970907L (sv

Inventor

James Roy Empfield

Thomas Michael Bare

Richard Bruce Sparks

Timothy Wayne Davenport

Jeffrey Alan Mckinney

Original Assignee

Astrazeneca Ab

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.)

1993-10-22

Filing date

1997-03-03

Publication date

2005-01-31

1993-10-22 Priority claimed from GB939321854A external-priority patent/GB9321854D0/en

1994-08-25 Priority claimed from GB9417171A external-priority patent/GB9417171D0/en

1997-03-03 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

1997-03-03 Publication of FI970907A0 publication Critical patent/FI970907A0/sv

1997-03-03 Publication of FI970907L publication Critical patent/FI970907L/sv

2005-01-31 Application granted granted Critical

2005-01-31 Publication of FI114916B publication Critical patent/FI114916B/sv

Links

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125000004122 cyclic group Chemical group 0.000 title description 3
206010015037 epilepsy Diseases 0.000 title description 2
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125000001072 heteroaryl group Chemical group 0.000 abstract description 18
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125000005605 benzo group Chemical group 0.000 abstract description 4
125000005843 halogen group Chemical group 0.000 abstract description 4
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125000003342 alkenyl group Chemical group 0.000 abstract description 2
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238000004458 analytical method Methods 0.000 description 83
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238000005481 NMR spectroscopy Methods 0.000 description 68
239000000706 filtrate Substances 0.000 description 58
239000002244 precipitate Substances 0.000 description 58
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 43
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239000011541 reaction mixture Substances 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
239000007858 starting material Substances 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
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238000005160 1H NMR spectroscopy Methods 0.000 description 24
125000003118 aryl group Chemical group 0.000 description 23
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238000002360 preparation method Methods 0.000 description 18
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238000002474 experimental method Methods 0.000 description 14
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DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 6
238000004809 thin layer chromatography Methods 0.000 description 6
DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 6
125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 description 5
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125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 5
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208000006011 Stroke Diseases 0.000 description 5
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125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
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230000000269 nucleophilic effect Effects 0.000 description 5
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238000001953 recrystallisation Methods 0.000 description 5
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239000011734 sodium Substances 0.000 description 5
230000001225 therapeutic effect Effects 0.000 description 5
238000003828 vacuum filtration Methods 0.000 description 5
KDXRMSBNDOIWBG-UHFFFAOYSA-N 2-(2-bromoethyl)-7-chloro-3,5-dihydropyridazino[4,5-b]quinoline-1,4,10-trione Chemical compound C=1C(Cl)=CC=C(C2=O)C=1NC1=C2C(=O)N(CCBr)NC1=O KDXRMSBNDOIWBG-UHFFFAOYSA-N 0.000 description 4
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
238000002844 melting Methods 0.000 description 4
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239000012038 nucleophile Substances 0.000 description 4
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238000000527 sonication Methods 0.000 description 4
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238000000159 protein binding assay Methods 0.000 description 2
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230000004044 response Effects 0.000 description 2
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238000012289 standard assay Methods 0.000 description 2
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UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
125000003564 m-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(C#N)=C1[H])C([H])([H])* 0.000 description 1
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
CDGNLUSBENXDGG-UHFFFAOYSA-N meta-Cresidine Chemical compound COC1=CC=C(N)C(C)=C1 CDGNLUSBENXDGG-UHFFFAOYSA-N 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
UEDZAAPTBWNOSU-UHFFFAOYSA-N methyl 5,7-dichloro-4-oxo-1h-quinoline-3-carboxylate Chemical compound C1=C(Cl)C=C(Cl)C2=C(O)C(C(=O)OC)=CN=C21 UEDZAAPTBWNOSU-UHFFFAOYSA-N 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
230000009525 mild injury Effects 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
230000009526 moderate injury Effects 0.000 description 1
230000037023 motor activity Effects 0.000 description 1
POSFMESELAWOIT-UHFFFAOYSA-N n-[2-(7-chloro-1,4,10-trioxo-3,5-dihydropyridazino[4,5-b]quinolin-2-yl)ethyl]-2-hydroxy-2-methylpropanamide Chemical compound N1C2=CC(Cl)=CC=C2C(=O)C2=C1C(=O)NN(CCNC(=O)C(C)(O)C)C2=O POSFMESELAWOIT-UHFFFAOYSA-N 0.000 description 1
210000003928 nasal cavity Anatomy 0.000 description 1
230000001338 necrotic effect Effects 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
230000003961 neuronal insult Effects 0.000 description 1
101150009274 nhr-1 gene Proteins 0.000 description 1
239000011356 non-aqueous organic solvent Substances 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
210000004940 nucleus Anatomy 0.000 description 1
125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
238000005580 one pot reaction Methods 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
239000013618 particulate matter Substances 0.000 description 1
230000037361 pathway Effects 0.000 description 1
125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
208000033300 perinatal asphyxia Diseases 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
229940038531 phenylhydrazine hydrochloride Drugs 0.000 description 1
125000004344 phenylpropyl group Chemical group 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
125000005544 phthalimido group Chemical class 0.000 description 1
230000001817 pituitary effect Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229960003975 potassium Drugs 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000001508 potassium citrate Substances 0.000 description 1
229960002635 potassium citrate Drugs 0.000 description 1
QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 description 1
235000011082 potassium citrates Nutrition 0.000 description 1
FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
239000003223 protective agent Substances 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
BWGUQNLLOGKYEI-UHFFFAOYSA-N pyridazino[4,5-b]quinoline Chemical class C1=NN=CC2=CC3=CC=CC=C3N=C21 BWGUQNLLOGKYEI-UHFFFAOYSA-N 0.000 description 1
BOYBQQBDCOIBIR-UHFFFAOYSA-N pyrido[2,3-f]cinnoline Chemical compound N1=CC=C2C3=NC=CC=C3C=CC2=N1 BOYBQQBDCOIBIR-UHFFFAOYSA-N 0.000 description 1
PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 description 1
DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 1
238000011552 rat model Methods 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
239000013558 reference substance Substances 0.000 description 1
238000012827 research and development Methods 0.000 description 1
238000012552 review Methods 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000012216 screening Methods 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
230000035945 sensitivity Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000035939 shock Effects 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
229940083542 sodium Drugs 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
235000019254 sodium formate Nutrition 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
239000004317 sodium nitrate Substances 0.000 description 1
235000010344 sodium nitrate Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
238000010186 staining Methods 0.000 description 1
238000007619 statistical method Methods 0.000 description 1
230000003335 steric effect Effects 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
210000000225 synapse Anatomy 0.000 description 1
210000002182 synaptic membrane Anatomy 0.000 description 1
210000003568 synaptosome Anatomy 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
DEZSJVJAVPWDDU-UHFFFAOYSA-N tert-butyl hydrogen carbonate;hydrazine Chemical class NN.CC(C)(C)OC(O)=O DEZSJVJAVPWDDU-UHFFFAOYSA-N 0.000 description 1
ZUDCEWRJJGQCEK-UHFFFAOYSA-N tert-butyl n-(3-phenylpropylamino)carbamate Chemical compound CC(C)(C)OC(=O)NNCCCC1=CC=CC=C1 ZUDCEWRJJGQCEK-UHFFFAOYSA-N 0.000 description 1
PNJRIORCUMSYLF-UHFFFAOYSA-N tert-butyl n-[(2-cyanophenyl)methylamino]carbamate Chemical compound CC(C)(C)OC(=O)NNCC1=CC=CC=C1C#N PNJRIORCUMSYLF-UHFFFAOYSA-N 0.000 description 1
FUXVUIAUSNGHTO-UHFFFAOYSA-N tert-butyl n-[(2-fluorophenyl)methylamino]carbamate Chemical compound CC(C)(C)OC(=O)NNCC1=CC=CC=C1F FUXVUIAUSNGHTO-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
YJBKVPRVZAQTPY-UHFFFAOYSA-J tetrachlorostannane;dihydrate Chemical compound O.O.Cl[Sn](Cl)(Cl)Cl YJBKVPRVZAQTPY-UHFFFAOYSA-J 0.000 description 1
GKTQKQTXHNUFSP-UHFFFAOYSA-N thieno[3,4-c]pyrrole-4,6-dione Chemical compound S1C=C2C(=O)NC(=O)C2=C1 GKTQKQTXHNUFSP-UHFFFAOYSA-N 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 1
FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
201000010875 transient cerebral ischemia Diseases 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
238000001665 trituration Methods 0.000 description 1
229960000281 trometamol Drugs 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000010930 yellow gold Substances 0.000 description 1
229910001097 yellow gold Inorganic materials 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- 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
- 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Diabetes (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Hematology (AREA)
Obesity (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Psychiatry (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Vascular Medicine (AREA)
Hospice & Palliative Care (AREA)
Urology & Nephrology (AREA)
Pain & Pain Management (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Quinoline Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Saccharide Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

FI970907A 1993-10-22 1997-03-03 Förfarande för framställning av 2-aryl-substituerade-4-hydroxi-1,2,5,10-tetrahydropyridazino [4,5-b] kinolin-1,10-dionderivat, som är terapeutiskt användbara vid vård av iskemiska sjukdomar i hjärnan FI114916B (sv)

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
GB9321854		1993-10-22
GB939321854A GB9321854D0 (en)	1993-10-22	1993-10-22	Pyridazino quinoline compounds
GB9417171A GB9417171D0 (en)	1994-08-25	1994-08-25	Pyridazino quinoline compounds
GB9417171		1994-08-25
GB9402295		1994-10-20
PCT/GB1994/002295 WO1995011244A1 (en)	1993-10-22	1994-10-20	Pyridazino quinoline compounds
FI961696		1996-04-18
FI961696A FI113865B (sv)	1993-10-22	1996-04-18	Förfarande för framställning av 2-arylsubstituerade-4-hydroxi-1,2,5,10-tetrahydropyridazino[4,5-b]-kinolin-1,10-dionderivat, som är terapeutiskt användbara vid vård av iskemiska sjukdomar i hjärnan

Publications (3)

Publication Number	Publication Date
FI970907A0 FI970907A0 (sv)	1997-03-03
FI970907L FI970907L (sv)	1997-03-03
FI114916B true FI114916B (sv)	2005-01-31

Family

ID=26303731

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
FI961696A FI113865B (sv)	1993-10-22	1996-04-18	Förfarande för framställning av 2-arylsubstituerade-4-hydroxi-1,2,5,10-tetrahydropyridazino[4,5-b]-kinolin-1,10-dionderivat, som är terapeutiskt användbara vid vård av iskemiska sjukdomar i hjärnan
FI970907A FI114916B (sv)	1993-10-22	1997-03-03	Förfarande för framställning av 2-aryl-substituerade-4-hydroxi-1,2,5,10-tetrahydropyridazino [4,5-b] kinolin-1,10-dionderivat, som är terapeutiskt användbara vid vård av iskemiska sjukdomar i hjärnan

Family Applications Before (1)

Application Number	Title	Priority Date	Filing Date
FI961696A FI113865B (sv)	1993-10-22	1996-04-18	Förfarande för framställning av 2-arylsubstituerade-4-hydroxi-1,2,5,10-tetrahydropyridazino[4,5-b]-kinolin-1,10-dionderivat, som är terapeutiskt användbara vid vård av iskemiska sjukdomar i hjärnan

Country Status (29)

Country	Link
US (3)	US5744471A (sv)
EP (2)	EP0724583B1 (sv)
JP (1)	JP3583132B2 (sv)
KR (1)	KR100261209B1 (sv)
CN (1)	CN1053189C (sv)
AT (2)	ATE295846T1 (sv)
AU (2)	AU688393B2 (sv)
CA (1)	CA2171332A1 (sv)
CZ (1)	CZ292311B6 (sv)
DE (2)	DE69426422T2 (sv)
DK (2)	DK0724583T3 (sv)
ES (2)	ES2154686T3 (sv)
FI (2)	FI113865B (sv)
GB (1)	GB9420590D0 (sv)
GR (1)	GR3035080T3 (sv)
HU (1)	HUT74161A (sv)
IL (1)	IL111266A (sv)
MY (2)	MY132875A (sv)
NO (1)	NO306995B1 (sv)
NZ (2)	NZ275472A (sv)
PL (1)	PL180679B1 (sv)
PT (2)	PT724583E (sv)
RU (1)	RU2168511C2 (sv)
SG (2)	SG92630A1 (sv)
SI (2)	SI1004582T1 (sv)
SK (1)	SK282491B6 (sv)
TW (1)	TW406082B (sv)
UA (1)	UA60291C2 (sv)
WO (1)	WO1995011244A1 (sv)

Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9420590D0 (en) *	1993-10-22	1994-11-30	Zeneca Ltd	Pyridazino quinoline compounds
GB9422894D0 (en) *	1994-11-12	1995-01-04	Zeneca Ltd	Pyridazino quinoline compounds
US6214826B1 (en)	1994-11-12	2001-04-10	Zeneca Limited	Pyridazino quinoline compounds
GB9507318D0 (en)	1995-04-07	1995-05-31	Zeneca Ltd	Alpha substituted pyridazino quinoline compounds
DE60026883T2 (de) *	1999-12-23	2006-11-23	Astrazeneca Ab	Methoden und zusammensetzungen zur behandlung von schmerzen
SI1244662T1 (sv) *	1999-12-23	2005-08-31	Astrazeneca Ab
US20030176435A1 (en) *	2002-12-17	2003-09-18	Brown Dean Gordon	Compounds and methods for the treatment of pain
US6787547B2 (en)	1999-12-23	2004-09-07	Astrazeneca Ab	Compound and method for the treatment of pain
JP2003519148A (ja) *	1999-12-23	2003-06-17	アストラゼネカ・アクチエボラーグ	痛みの処置のための化合物および方法
US6730675B2 (en)	1999-12-23	2004-05-04	Astrazeneca Ab	Compounds and methods for the treatment of pain
WO2001047927A1 (en) *	1999-12-23	2001-07-05	Astrazeneca Ab	Compound and method for the treatment of pain
AU2420101A (en) *	1999-12-23	2001-07-09	Astrazeneca Ab	Method and composition for the treatment of pain
HK1048767A1 (zh) *	1999-12-23	2003-04-17	阿斯特拉曾尼卡有限公司	治疗疼痛的方法和组合物
JP2003519147A (ja) *	1999-12-23	2003-06-17	アストラゼネカ・アクチエボラーグ	痛みの処置のための化合物および方法
AU2566101A (en) *	1999-12-23	2001-07-09	Astrazeneca Ab	Compounds and methods for the treatment of pain
US6943165B2 (en) *	1999-12-23	2005-09-13	Astrazeneca Ab	Compound and method for the treatment of pain
US6403818B1 (en)	2000-02-28	2002-06-11	Eisai Co., Ltd.	Process for producing α-hydroxy-carbonyl compound
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1994
- 1994-10-12 GB GB9420590A patent/GB9420590D0/en active Pending
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1997
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1999
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Also Published As

Publication number	Publication date
DK0724583T3 (da)	2001-03-05
IL111266A (en)	2002-03-10
DE69434380D1 (de)	2005-06-23
ATE295846T1 (de)	2005-06-15
SK50496A3 (en)	1997-03-05
FI970907A0 (sv)	1997-03-03
KR100261209B1 (ko)	2000-09-01
AU6899998A (en)	1998-07-30
NZ275472A (en)	1998-03-25
ES2241513T3 (es)	2005-11-01
AU721139B2 (en)	2000-06-22
CN1138332A (zh)	1996-12-18
CN1053189C (zh)	2000-06-07
DE69434380T2 (de)	2006-05-04
SI1004582T1 (sv)	2005-08-31
WO1995011244A1 (en)	1995-04-27
HK1013997A1 (en)	1999-09-17
US6103721A (en)	2000-08-15
US6232313B1 (en)	2001-05-15
EP1004582A2 (en)	2000-05-31
EP0724583B1 (en)	2000-12-13
FI961696A0 (sv)	1996-04-18
DE69426422T2 (de)	2001-05-10
PT724583E (pt)	2001-03-30
EP0724583A1 (en)	1996-08-07
FI970907L (sv)	1997-03-03
DE69426422D1 (de)	2001-01-18
EP1004582A3 (en)	2000-08-30
AU688393B2 (en)	1998-03-12
SG92630A1 (en)	2002-11-19
UA60291C2 (uk)	2003-10-15
CZ292311B6 (cs)	2003-09-17
EP1004582B1 (en)	2005-05-18
US5744471A (en)	1998-04-28
PT1004582E (pt)	2005-09-30
TW406082B (en)	2000-09-21
FI113865B (sv)	2004-06-30
NZ329303A (en)	2000-01-28
AU7944094A (en)	1995-05-08
DK1004582T3 (da)	2005-08-15
CZ113896A3 (en)	1996-09-11
PL314041A1 (en)	1996-08-05
IL111266A0 (en)	1994-12-29
JPH09504519A (ja)	1997-05-06
GR3035080T3 (en)	2001-03-30
CA2171332A1 (en)	1995-04-27
ATE198072T1 (de)	2000-12-15
JP3583132B2 (ja)	2004-10-27
SK282491B6 (sk)	2002-02-05
NO961584D0 (no)	1996-04-19
SG59971A1 (en)	1999-02-22
GB9420590D0 (en)	1994-11-30
PL180679B1 (en)	2001-03-30
NO961584L (no)	1996-04-19
SI0724583T1 (en)	2001-04-30
HU9600889D0 (en)	1996-06-28
NO306995B1 (no)	2000-01-24
FI961696L (sv)	1996-04-18
MY132875A (en)	2007-10-31
RU2168511C2 (ru)	2001-06-10
HUT74161A (en)	1996-11-28
ES2154686T3 (es)	2001-04-16
MY124316A (en)	2006-06-30

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FI114916B (sv)	2005-01-31	Förfarande för framställning av 2-aryl-substituerade-4-hydroxi-1,2,5,10-tetrahydropyridazino [4,5-b] kinolin-1,10-dionderivat, som är terapeutiskt användbara vid vård av iskemiska sjukdomar i hjärnan
AU638005B2 (en)	1993-06-17	5-alkylquinolonecarboxylic acids
SK7032003A3 (en)	2004-04-06	Substituted pyrroloquinolines and pyridoquinolines as serotonin agonists and antagonists
US5837705A (en)	1998-11-17	Alpha-substituted pyridazino quinoline compounds
KR101272263B1 (ko)	2013-06-13	감염 방지제로서 사용되는8-메톡시-9ｈ-이소티아졸로［5,4-ｂ］퀴놀린-3,4-디온 및관련 화합물
DE69823493T2 (de)	2009-09-24	Tetrahydropyridoverbindungen
EP3227291B1 (en)	2019-05-15	N-substituted beta-carbolinium compounds as potent p-glycoprotein inducers
JPH0311067A (ja)	1991-01-18	興奮性アミノ酸拮抗剤
IE56839B1 (en)	1992-01-01	New 1h,3h-pyrrolo(1,2-c)thiazole derivatives,their preparation and compositions containing them
AU705938B2 (en)	1999-06-03	Pyridazino quinoline compounds
EP0550016A1 (en)	1993-07-07	Novel quinolone carboxylic acid derivatives and processes for preparing same
US6214826B1 (en)	2001-04-10	Pyridazino quinoline compounds
KR100295148B1 (ko)	2001-09-07	피리다지노퀴놀린 화합물
CN120965801A (zh)	2025-11-18	一类环状brd4蛋白降解剂及其用途
RU2279432C2 (ru)	2006-07-10	Производные пиридазинохинолина
JPS61112083A (ja)	1986-05-30	チエノトリアジン類
HK1013997B (en)	2002-02-15	Pyridazino quinoline compounds

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