WO2003055865A1 - Quinazolinone derivative - Google Patents
Quinazolinone derivative Download PDFInfo
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- WO2003055865A1 WO2003055865A1 PCT/JP2002/013286 JP0213286W WO03055865A1 WO 2003055865 A1 WO2003055865 A1 WO 2003055865A1 JP 0213286 W JP0213286 W JP 0213286W WO 03055865 A1 WO03055865 A1 WO 03055865A1
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- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
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- C07D401/06—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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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Definitions
- This invention relates to a novel quinazolinone derivative having pharmacological activity, to a process for their production and to a pharmaceutical composition containing the same.
- Poly (adenosine 5' -diphospho-ribose) polymerase ["poly (ADP-ribose) polymerase” or “PARP”, which is also sometimes called “PARS” for “poly (ADP-ribose) synthetase”] is an enzyme located in the nuclei of cells of various organs, including muscle, heart andbrain cells . PARPplays a physiological role in the repair of strand breaks in DNA. Once activated by damaged DNA fragments,
- PARP catalyzes the attachment of up to 100 ADP-ribose units to a variety of nuclear proteins, including histones and PARP itself.
- This invention relates to a novel quinazolinone compound, which has pharmaceutical activity such as PARP inhibiting activity, to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.
- One object of this invention is to provide the novel quinazolinone compound, which has a PARP inhibiting activity. Another object of this invention is to- provide a process for production of the quinazolinone compound.
- a further object of this invention is to provide a pharmaceutical composition containing the quinazolinone compound as an active ingredient.
- Still further object of this invention is to provide a use of the quinazolinone compound for manufacturing a medicament for treating or preventing various diseases, or a method of treating or preventing various diseases by administering the quinazolinone compound in an effective amount to inhibit PARP activity.
- the quinazolinone compound of this invention can be represented by the following formula (I):
- R 1 is substituted cyclic amino groups, optionally substituted carbocyclic group or optionally substituted amino group, R 2 is substituent, n means an integer of 0 to 4, and L 1 is (1) cyclo (lower) alkylene, (2) cyclo (lower) alkenylene, (3) diradical of saturated- or unsaturated monocyclic group with one or more nitrogen atom(s) , which is obtained after removal of one hydrogen atomfromsaidmonocyclic group, or (4) -N(R 3 )-L 2 - (wherein R 3 is hydrogen or lower alkyl, and L 2 is lower alkylene or lower alkenylene) ] , or its prodrug, or a salt thereof.
- the compound (I) or its prodrug, or a salt thereof can be prepared by the following processes.
- the compounds may be prodrugs or their salts.
- R 1 , R 2 , n and L 1 are each as defined above.
- the compound (I) or a salt thereof can be produced by subjecting the compound (II) to cyclization reaction in the presence of base, such as inorganic bases, for example, an alkali metal [e.g., sodium or potassium] , alkoxide, hydroxide, carbonate or bicarbonate thereof, or organic bases such as a trialkylamine [e.g., trimethylamine or triethylamine] or the like.
- base such as inorganic bases, for example, an alkali metal [e.g., sodium or potassium] , alkoxide, hydroxide, carbonate or bicarbonate thereof, or organic bases such as a trialkylamine [e.g., trimethylamine or triethylamine] or the like.
- the reaction is usually carried out in a conventional solvent such as water, an alcohol (e.g., methanol, ethanol or isopropyl alcohol) , ether, tetrahydrofuran, dioxane, diethylether, amide (e.g., N, N-dimethylformamide, N, N-dimethylacetamide) , nitrile (e.g. , acetonitrile) , or any other organic solvent which does not adversely affect the reaction.
- a conventional solvent such as water, an alcohol (e.g., methanol, ethanol or isopropyl alcohol) , ether, tetrahydrofuran, dioxane, diethylether, amide (e.g., N, N-dimethylformamide, N, N-dimethylacetamide) , nitrile (e.g. , acetonitrile) , or any other organic solvent which does not adversely affect the reaction.
- R 1 and n are each as defined above.
- the compound (I-a) or a salt thereof can be produced by reacting the compound (III) or a salt thereof and compound (VI) or a salt thereof in the presence of base, such as inorganic bases, for example, an alkali metal [e.g., sodium or potassium] , alkoxide, hydroxide, carbonate orbicarbonate thereof, or organic bases such as a trialkylamine [e.g., trimethylamine or triethylamine] or the like.
- base such as inorganic bases, for example, an alkali metal [e.g., sodium or potassium] , alkoxide, hydroxide, carbonate orbicarbonate thereof, or organic bases such as a trialkylamine [e.g., trimethylamine or triethylamine] or the like.
- the reaction is usually carried out in a conventional solvent such as an alcohol (e.g., methanol, ethanol or isopropyl alcohol) , tetrahydrofuran, dioxane, diethylether, amide (e.g., N,N-dimethylformamide, N, N-dimethylacetamide) , nitrile (e.g., acetonitrile) , or any other organic solvent which does not adversely affect the reaction.
- a conventional solvent such as an alcohol (e.g., methanol, ethanol or isopropyl alcohol) , tetrahydrofuran, dioxane, diethylether, amide (e.g., N,N-dimethylformamide, N, N-dimethylacetamide) , nitrile (e.g., acetonitrile) , or any other organic solvent which does not adversely affect the reaction.
- the reaction may be usually carried out under cooling to heating since the
- the compounds of the present invention can be purified by any conventional purification methods employed for purifying organic compounds, such as recrystallization, column chromatography, thin-layer chromatography, high-performance liquidchromatography andthe like.
- the compounds canbe identified by conventional methods such as NMR spectrography, mass spectrography, IR spectrography, elemental analysis, and measurement of melting point.
- R 1 , R 2 , n and L 1 are each as defined above.
- Suitable salt of the compound (I) of the present invention are pharmaceutically acceptable conventional non-toxic salts and can be an organic acid addition salt (e.g. formate, acetate, trifluoroacetate, maleate, tartrate, oxalate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.), an inorganic acid addition salt (e.g. hydrochloride, hydrobromide, sulfate, phosphate, etc.), a salt with an amino acid (e.g. aspartic acid salt, glutamic acid salt, etc.), or the like.
- organic acid addition salt e.g. formate, acetate, trifluoroacetate, maleate, tartrate, oxalate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.
- an inorganic acid addition salt e.g. hydrochloride, hydrobromide,
- prodrug means the derivative of compound of the present invention having a chemically or metabolically degradable group, which becomes pharmaceutically active after biotransformation.
- the compound (I) of the present invention may contain one or more asymmetric centers and thus they can exist as enantiomers or diastereoisomers . Further more certain the compound (I) which contains alkenyl groups may exist as cis- or trans-isomers . In each instance, the invention includes both mixtures and separate individual isomers.
- the compound (I) may also exist in tautomeric forms, and the invention includes both mixtures and separate individual tautomers.
- the compound (I) or a salt thereof can be in a form of a solvate, which is includedwithin the scope of thepresent invention.
- the solvate preferably includes a hydrate or an ethanolate.
- radiolabelled derivative of the compound (I) which is suitable for biological studies, may be included in the scope of invention.
- lower means a group having 1 to 6 carbon atom(s) , unless otherwise provided.
- Suitable “lower alkyl” includes a straight or branched alkyl having 1 to 6 carbon atom(s) , in particular 1 or 2 carbon atom(s) .
- Preferable examples whichmaybe mentioned aremethyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl and hexyl .
- Suitable "lower alkoxy” includes straight or branched alkoxy having 1 to 6 carbon atom(s) , in particular 1 or 2 carbon atom(s) .
- Preferable examples which may be mentioned are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, iso-butoxy, sec-butoxy and tert-butoxy, preferably methoxy.
- Suitable “lower alkylamino” include mono (lower) alkylamino and di (low.er) alkylamino .
- Preferable examples which may be mentioned are methylamino, dimethylamino, ethylamino, dimethylamino, n-propylamino, isopropylamino, n-butylamino, iso-butylamino, sec-butylamino and tert-butylamino, preferably dimethylamino and diethylamino.
- Suitable "aryl” may be intended to mean a mono-, di- or polynuclear aromatic radical having preferably 6 to 12 carbon atoms , such as phenyl, naphthyl, tetrahydronaphthyl, indenyl, indanyl (1, 2-dihydroindenyl) , fluorenyl and the like, preferably phenyl or naphthyl .
- halogen means fluoro, chloro, bromo or iodo.
- Suitable “halo (lower) alkyl” contains 1 to 4 carbon atom(s) , in particular 1 or 2 carbon atom(s), and 1 to 9 halogen atom(s), in particular 1 to 5 identical or different halogen atom(s), preferably fluorine, chlorine and bromine, in particular fluorine and chlorine.
- Preferable examples which may be mentioned are trifluoromethyl, trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, chloromethyl, bromomethyl, 1-fluoroethyl, 2-fluoroethyl, 2, 2-difluoroethyl, 2, 2, 2-trifluoroethyl, 2, 2, 2-trichloroethyl and pentafluoroethyl, preferably trifluoromethyl .
- the term "carbocyclic group” is intended to mean cyclo (lower) alkyl or cyclo (lower) alkenyl .
- Suitable "cyclo (lower) alkyl” and “cyclo (lower) alkyl moiety" in the term “cyclo (lower) alkylene” includes a saturated carbocycle having 3 to 7 carbon atoms, in particular 5 to 6 carbon atoms.
- Preferable examples whichmaybementioned are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl, preferably cyclopropyl and cyclohexyl (e.g., 1,3- cyclohexylene, 1, 4-cyclohexylene, etc.).
- Suitable "cyclo (lower) alkenyl” and “cyclo (lower) alkenyl moiety" in the term “cyclo (lower) alkenylene” includes a partially saturated carbocycle having 3 to 7 carbon atoms, in particular 5 to 6 carbon atoms.
- Preferable examples which may be mentioned are cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl and cycloheptenyl, preferably cyclopentenyl and cyclohexenyl.
- cyclo (lower) alkylene are cyclopentenylene (e.g., 1, 3-cyclocyclopent-l-enylene, etc.), cyclohexenylene (e.g., 1,3- , cyclohex-1-enylene, etc.).
- heteroaryl and heteroaryl moiety in the terms “heteroaryl (lower) alkyl” and “heteroaromatic acyl” is intended to mean 5- to 7-memberedrings having preferably 1 to 3 heteroatom (s) , in particular 1 or 2 identical or different heteroatom (s) .
- Heteroatoms in the heteroaryl are oxygen, sulfur or nitrogen.
- Examples which may be mentioned are furyl, thienyl, pyrazolyl, imidazolyl, triazolyl (e.g., 1,2,3- and 1, 2, 4-triazolyl, etc.), isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl (e.g., 1,3,4-, and 1, 2, 5-oxadiazolyl, etc.), azepinyl, pyrrolyl, pyridinyl, piperazinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl (e.g., 1,3,5-, 1, 2, 4- and 1,2, 3-triazinyl, etc.), oxazinyl (e.g., 1,2,4- and 1, 2, 6-oxazinyl, etc.), oxepinyl, thiepinyl and diazepinyl (e.g., 1, 2, 4-diazepinyl
- Suitable "cyclic amino group” are heteroaromatic or aliphatic ring systems having one or more nitrogen atoms as the heteroatom, in which the heterocyclic rings can be saturated or unsaturated, can be one ring system or several fused ring systems, and optionally contain further heteroatoms, such as nitrogen, oxygen and sulfur and the like. Cyclic amino groups can furthermore also denote a spiro ring or a bridged ring system.
- the number of atoms which form cyclic amino groups is not limited, for example in the case of a single-ring system, they comprise 3 to 8 atoms, and in the case of a three-ring system, they comprise 7 to 11 atoms.
- cyclic amino group examples which may be mentioned of cyclic amino group with saturated monocyclic groups with one or more nitrogen atom(s) as the heteroatom are azetidinyl (3-azetidinyl) , pyrrolidinyl (e.g., 1- and 3-pyrrolidinyl, etc.), piperidyl (e.g., 1- and 4-piperidyl, etc.), homopiperidino (e.g., hexahydro-lH-azepin-1-yl, etc.), homopiperazinyl (e.g., hexahydro-lH-1, 4-diazepin-l-yl, etc.), imidazolidinyl (e.g.
- cyclic amino group with unsaturated monocyclic groups with one or more nitrogen atom(s) as the heteroatom examples which may be mentioned are pyrrolinyl (e.g., 2-pyrrolin-l-yl, etc.), pyrrolyl (e.g., 1-pyrrolyl, etc), tetrahydropridinyl (e.g., 3, 6-dihydro-l (2H) -pyridinyl, etc.), pyridinyl (e.g., 2-pyridinyl, etc.)-, tetrahydroazepinyl (e.g., 2 , 3 , 6, 7-tetrahydro-lH-azepin-l-yl,
- imidazolyl (1-imidazolyl)
- pyrazolyl triazolyl, tetrazolyl, tetrazolyl, pyrimidinyl
- pyrazinyl pyridazinyl
- dihydro-pyridazinyl e.g., 1, 2-dihydro-pyridazin-l-yl, etc.
- dihydro-pyrimidinyl e.g., 1, 2-dihydro-pyrimidin-l-yl, etc.
- cyclic amino groups with saturated and unsaturated monocyclic groups with 1 to 3 nitrogen atom(s) and 1 or 2 sulfur atom(s) as heteroatoms are thiazolidinyl (e.g., 3-thiazolidinyl, etc.), isothiazolinyl (e.g., 2-isothiazolinyl, etc.) and thiomorpholino;
- cyclic amino groups with saturated and unsaturated monocyclic groups with 1 to 3 nitrogen atom(s) and 1 or 2 oxygen atom(s) as heteroatoms are oxazolyl, isoxazolyl, oxadiazolyl (e.g., 1, 2, 4-oxadiazolyl, and 1, 3, 4-oxadiazolyl) or morpholinyl;
- cyclic amino groups with saturated and unsaturated fused cyclic groups are indolyl (e.g., 1-indolyl,' etc.)., dihydrobenzimidazolyl (e.g., 1, 2-dihydrobenzimidazol-l-yl, etc.), perhydropyrrolo [1, 2-a] pyrazinyl (e.g. , perhydropyrrolo [1, 2-a] pyrazin-2-yl, etc. ) , tetrahydrobenzo [f] isoquinolinyl (e.g.,
- 1,4,5, 6-tetrahydrobenzo [f] isoquinolin-3 (2H) -yl, etc. ) , hexahydrobenz [f] isoquinolinyl (e.g., cis- and trans-1, 4, 4a, 5, 6, lOb-hexahydrobenz [f] isoquinolin-3 (2H) -yl, etc.), tetrahydropyrido [3, 4-b] indolyl (e.g.,
- cyclic amino groups with spirocyclic groups are azaspiro [4, 5] decanyl (e.g., 2-azaspiro [4, 5] decan-2-yl, etc.), spiro [lH-indene-1, 4 ' -piperidinyl] (e.g. , spiro [lH-indene-1, 4 ' -piperidin-1 ' -yl] , etc.), and dihydrospiro [lH-indene-1, 4 ' -piperidinyl] (e.g.,
- cyclic amino groups bridged heterocyclic groups are azabicyclo [2, 2, 1] heptanyl (e.g., 2-azabicyclo [2, 2, 1] heptan-7-yl, etc.) and diazabicyclo [2.2.1] heptyl (e.g., 2, 5-diazabicyclo [2.2.1] hept-2-yl, etc.) .
- preferable "cyclic amino group" included in R 1 is above-mentioned (1) or (2), in which the most preferable one may be piperidinyl, tetrahydropyridinyl and piperazinyl.
- azetidinylene e.g., 1,2- or 1, 3-azetidinylene
- pyrrolidinylene e.g., 1,2- or 1,3- pyrrolidinylene
- piperidinylene e.g., 1,3- or 1, 4-piperidinylene
- the compound possessing PARP inhibiting activity such as the compound (I) or a pharmaceutically acceptable salt thereof of this invention is useful in treating and preventing various diseases ascribed by N DA- and NO-induced toxicity.
- Such diseases include, for example, tissue damage resulting from cell damage or death due to necrosis or apoptosis; neural tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases; neurodegenerative diseases; head trauma; stroke; Alzheimer's disease; Parkinson's disease; epilepsy; Amyotrophic lateral Scleosis (ALS) ; Huntington' s disease; schizophrenia; chronicpain; ischemia and neuronal loss following hypoxia; hypoglycemia; ischemia; trauma; and nervous insult.
- tissue damage resulting from cell damage or death due to necrosis or apoptosis include, for example, tissue damage resulting from cell damage or death due to necrosis or apoptosis; neural tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases; neurodegenerative diseases; head trauma; stroke; Alzheimer's disease; Parkinson's disease; epilepsy; Amyotrophic lateral Scleosis (ALS) ; Huntington' s disease; schizophrenia
- the compound possessing PARP inhibiting activity such as the compound (I) or a pharmaceutically acceptable salt thereof of this invention is useful in treatment and prevention of previously ischemic heart or skeleton muscle tissue. It is also known that PARP is thought to play a role in enhancing DNA repair. So, the compound possessing PARP inhibiting activity, such as the compound (I) or a pharmaceutically acceptable salt thereof of this invention is effective in treating and preventing radiosensitizing hypoxic tumor cells; tumor cells from recovering from potentially lethal damage of DNA after radiation therapy.
- the compound possessing PARP inhibiting activity such as the compound (I) or a pharmaceutically acceptable salt thereof of this invention is useful in extending the life-span and proliferative capacity of cells and altering gene expression of senescent cells. It is useful for treating and preventing skin aging; Alzheimer's diseases; arteriosclerosis; osteoarthritis; osteoporosis; muscular dystrophy; degenerative diseases of skeletal muscle involving replicative senescence; age-related macular degeneration; immune senescence; AIDS; and other immune senescence diseases.
- the compound possessing PARP inhibiting activity such as the compound (I) or a pharmaceutically acceptable salt thereof of this invention is effective in treating and preventing inflammatory bowel disorders (e.g., colitis); arthritis; diabetes; endotoxic shock; septic shock; and tumor. Also, it is useful in reducing proliferation of tumor cells and making synergistic effect when tumor cells are co-treated with an alkylamine drug.
- the compound possessing PARP inhibiting activity such as the compound (I) of this invention or a pharmaceutically acceptable salt thereof of this invention is effective in treating and preventing pituitary apoplexy; conjunctivitis; retinoblastoma; retinopathy; acute retinal necrosis syndrome; Sjogren's syndrome.
- the compound (I), its prodrug, or a salt thereof can be administered alone or in the form of a mixture, preferably, with a pharmaceutical vehicle or carrier.
- the active ingredient of this invention can be used in the form of a pharmaceutical preparation, for example, in solid, semisolid or liquid form, which contains a compound (I) , as an active ingredient, in admixture with an organic or inorganic carrier or excipient suitable for external (topical) , enteral, intravenous, intramuscular, parenteral or intramucous applications.
- a pharmaceutical preparation for example, in solid, semisolid or liquid form, which contains a compound (I) , as an active ingredient, in admixture with an organic or inorganic carrier or excipient suitable for external (topical) , enteral, intravenous, intramuscular, parenteral or intramucous applications.
- the active ingredient can be formulated, for example, with the conventional non-toxic, pharmaceutically acceptable carriers for ointment, cream, plaster, tablets, pellets, capsules, suppositories, solution (saline, for example) , emulsion, suspension (olive oil, for example) , aerosols, pills, powders, syrups, injections, troches, cataplasms, aromatic waters, lotions, buccal tablets, sublingual tablets, nasal drops and any other form suitable for use.
- the carriers which can be used are water, wax, glucose, lactose, gum acacia, gelatin, mannitol, starch paster, magnesium trisilicate, talc, corn starch, keratin, paraffin, colloidal silica, potato starch, urea and other carriers suitable for use in manufacturing preparations, in solid, semisolid, or liquid form, and in addition auxiliary, stabilizing, thickening and coloring agents and perfumes may be used.
- the active compound is included in a pharmaceutical composition in an effective amount sufficient to produce the desired effect upon the process or condition of the diseases.
- the active ingredient can be formulated into, for example, preparations for oral application, preparations for injection, preparations for external application, preparations for inhalation, preparations for application to mucous membranes.
- Mammals which may be treated by the present invention include livestock mammals such as cows, horses, etc., domestic animals such as dogs, cats, rats, etc. and humans, preferably humans.
- While the dosage of therapeutically effective amount of the compound (I) will vary depending upon the age and condition of each individual patient, an average single dose to a human patient of about 0.01 mg, 0.1 mg, 1 mg, 10 mg, 50 mg, 100 mg, 250 mg, 500 mg, and 1000 mg of the compound (I) may be effective for treating the above-mentioned diseases. In general, amounts between 0.01 mg/body and about 1,000 mg/body may be administered per day.
- Test Compound Compound A:
- the recombinant human PARP (5.3mg protein/ml) were incubated with a test compound in a 100 ⁇ l reaction buffer containing the indicated concentration of 1 mCi/ml 32 P-NAD, 50mM Tris-HCl, 25mM MgCl 2 , lmM DTT (dithiothreitol) , 0.05mM AD (nicotinamido adenine dinucleotide) , lmg/ml activated DNA, pH8.0. Incubation was for 15 minutes at a room temperature and the reaction was stopped by the addition of 200 ⁇ 1 of ice-cold 20% trichloroacetic acid followed by rapid filtration through GF/B filters. The filters were treated with scintillation fluid and acid-insoluble counts were measured for quantification of unit activity.
- PARP inhibitory activity (%) [1- (enzyme activity with test compound) / (enzyme activity with vehicle)] xlOO
- This invention relates to novel Quinazolinone compounds had a potent PARP inhibitory activity.
- PARP inhibitors including this invention relates to novel quinazolinone compounds were effective in preventing reduction of striate DA and its metabolite induced by MPTP treatment in mice. Therefore, it suggests that these compounds may have protective benefit in the treatment of neurodegenerative disease such as Parkinson's disease.
- N-ethyl-N,N-diisopropylamine (0.174mL, l.OOmmol) and 0- (7-azabenzotriazol-l-yl) -N,N,N' ,N' -tetramethyluronium hexafluorophosphate (380 mg, 1.00 mmol) were added to a solution of 2-aminobenzamide (136 mg, 1.00 mmol) and
- Example 5 Triethylamine (1.54 mL, 11.1 mmol) was added to a suspension of 2-chloro-4 (3H) -quinazolinone (100 mg, 0.554 mmol) and 2- (4-phenyl-3, 6-dihydro-l (2H) -pyridinyl) ethanamine dihydrochloride (229 mg, 0.831 mmol) in N,N-dimethylformamide (3 mL) , and the mixture was heated at 100°C for 3 hours. Cooled to room temperature, and the reaction were quenched with water, and the product was extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulfate.
- Example 6 The following compounds were prepared in a similar manner to that of Example 5.
- Triethylamine (1.40 mL, 10.0 mmol) was added to a suspension of 2-chloro-4 (3H) -quinazolinone (181 mg, 1.00 mmol) and N,N-dimethyl-l, 2-ethanediamine (0.196 mL, 1.50 mmol) in dioxane (5 L) , and the mixture was heated at reflux for 2 hours. Cooled to room temperature, and the reaction were quenched with water, and the product was extracted with ethyl acetate . The organic layer was washed with water and dried over sodium sulfate.
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Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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US10/499,348 US20050043333A1 (en) | 2001-12-24 | 2002-12-19 | Quinazolinone derivative |
JP2003556396A JP2005515216A (en) | 2001-12-24 | 2002-12-19 | Quinazolinone derivatives |
EP02788856A EP1458688A1 (en) | 2001-12-24 | 2002-12-19 | Quinazolinone derivative |
CA002471348A CA2471348A1 (en) | 2001-12-24 | 2002-12-19 | Quinazolinone derivative |
AU2002353537A AU2002353537A1 (en) | 2001-12-24 | 2002-12-19 | Quinazolinone derivative |
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AUPR9756 | 2001-12-24 | ||
AUPR9756A AUPR975601A0 (en) | 2001-12-24 | 2001-12-24 | Quinazolinone derivatives |
Publications (1)
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WO2003055865A1 true WO2003055865A1 (en) | 2003-07-10 |
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ID=3833368
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PCT/JP2002/013286 WO2003055865A1 (en) | 2001-12-24 | 2002-12-19 | Quinazolinone derivative |
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US (1) | US20050043333A1 (en) |
EP (1) | EP1458688A1 (en) |
JP (1) | JP2005515216A (en) |
AU (1) | AUPR975601A0 (en) |
CA (1) | CA2471348A1 (en) |
WO (1) | WO2003055865A1 (en) |
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WO2006003146A1 (en) * | 2004-06-30 | 2006-01-12 | Janssen Pharmaceutica N.V. | Quinazolinone derivatives as parp inhibitors |
WO2006072588A1 (en) * | 2005-01-07 | 2006-07-13 | Laboratorios Del Dr. Esteve S.A. | Substituted 2-amino-quinazolin-4-cn compounds for use in the treatment of cns disorders, pain, stroke, addiction and epilepsy, their preaparation and use as intermediates |
US7151102B2 (en) | 2000-10-30 | 2006-12-19 | Kudos Pharmaceuticals Limited | Phthalazinone derivatives |
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WO2009041566A1 (en) * | 2007-09-26 | 2009-04-02 | Santen Pharmaceutical Co., Ltd. | Preventive or remedy for posterior eye diseases containing quinazolinone derivative or quinoxaline derivative as the active ingredient |
WO2009041565A1 (en) * | 2007-09-26 | 2009-04-02 | Santen Pharmaceutical Co., Ltd. | Quinazolinone derivative, and prophylactic or therapeutic agent for corneal/conjunctival disorder comprising quinazolinone derivative as active ingredient |
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US8129380B2 (en) | 2008-01-23 | 2012-03-06 | Astrazeneca Ab | Phthalazinone derivatives |
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US8168644B2 (en) | 2008-03-27 | 2012-05-01 | Janssen Pharmaceutica Nv | Quinazolinone derivatives as tubulin polymerization inhibitors |
US8299256B2 (en) | 2007-03-08 | 2012-10-30 | Janssen Pharmaceutica Nv | Quinolinone derivatives as PARP and TANK inhibitors |
WO2013008872A1 (en) | 2011-07-13 | 2013-01-17 | 参天製薬株式会社 | Novel compound having parp inhibitory activity |
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HUE061595T2 (en) | 2017-12-21 | 2023-07-28 | Ribon Therapeutics Inc | Quinazolinones as parp14 inhibitors |
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- 2002-12-19 JP JP2003556396A patent/JP2005515216A/en not_active Withdrawn
- 2002-12-19 US US10/499,348 patent/US20050043333A1/en not_active Abandoned
- 2002-12-19 CA CA002471348A patent/CA2471348A1/en not_active Abandoned
- 2002-12-19 EP EP02788856A patent/EP1458688A1/en not_active Withdrawn
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WO1995024379A1 (en) * | 1994-03-09 | 1995-09-14 | Newcastle University Ventures Limited | Benzamide analogs, useful as parp (adp-ribosyltransferase, adprt) dna repair enzyme inhibitors |
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US20050043333A1 (en) | 2005-02-24 |
JP2005515216A (en) | 2005-05-26 |
EP1458688A1 (en) | 2004-09-22 |
AUPR975601A0 (en) | 2002-01-31 |
CA2471348A1 (en) | 2003-07-10 |
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