JP4574860B2 - ４−オキソ−３，５−ジヒドロ−４Ｈ−ピリダジノ［４，５−ｂ］インドール−１−カルボキサミド誘導体、それらの製造、および治療におけるそれらの適用 - Google Patents
４−オキソ−３，５−ジヒドロ−４Ｈ−ピリダジノ［４，５−ｂ］インドール−１−カルボキサミド誘導体、それらの製造、および治療におけるそれらの適用 Download PDFInfo
- Publication number
- JP4574860B2 JP4574860B2 JP2000596007A JP2000596007A JP4574860B2 JP 4574860 B2 JP4574860 B2 JP 4574860B2 JP 2000596007 A JP2000596007 A JP 2000596007A JP 2000596007 A JP2000596007 A JP 2000596007A JP 4574860 B2 JP4574860 B2 JP 4574860B2
- Authority
- JP
- Japan
- Prior art keywords
- mmol
- indole
- oxo
- pyridazino
- dihydro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000002360 preparation method Methods 0.000 title description 3
- KUVBJWGMAORROJ-UHFFFAOYSA-N 4-oxo-3,5-dihydropyridazino[4,5-b]indole-1-carboxamide Chemical class N1C2=CC=CC=C2C2=C1C(=O)NN=C2C(=O)N KUVBJWGMAORROJ-UHFFFAOYSA-N 0.000 title 1
- 238000002560 therapeutic procedure Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 38
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 239000000243 solution Substances 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical group O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 13
- 230000008018 melting Effects 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000003480 eluent Substances 0.000 description 10
- 239000000377 silicon dioxide Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 150000004696 coordination complex Chemical class 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 239000002198 insoluble material Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 4
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- YAIVDGZDNCFDNH-UHFFFAOYSA-N ethyl 6-chloro-3-(2-ethoxy-2-oxoacetyl)-1-methylindole-2-carboxylate Chemical compound ClC1=CC=C2C(C(=O)C(=O)OCC)=C(C(=O)OCC)N(C)C2=C1 YAIVDGZDNCFDNH-UHFFFAOYSA-N 0.000 description 3
- BZTTWVSCPUWUPH-UHFFFAOYSA-N ethyl 7-chloro-3-(3-chlorophenyl)-5-methyl-4-oxopyridazino[4,5-b]indole-1-carboxylate Chemical compound O=C1C=2N(C)C3=CC(Cl)=CC=C3C=2C(C(=O)OCC)=NN1C1=CC=CC(Cl)=C1 BZTTWVSCPUWUPH-UHFFFAOYSA-N 0.000 description 3
- 210000000744 eyelid Anatomy 0.000 description 3
- 210000000256 facial nerve Anatomy 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000000508 neurotrophic effect Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- RAFKIFPDMATLBG-UHFFFAOYSA-N 7-chloro-3-(3-chlorophenyl)-5-methyl-1-(pyrrolidine-1-carbonyl)pyridazino[4,5-b]indol-4-one Chemical compound O=C1C=2N(C)C3=CC(Cl)=CC=C3C=2C(C(=O)N2CCCC2)=NN1C1=CC=CC(Cl)=C1 RAFKIFPDMATLBG-UHFFFAOYSA-N 0.000 description 2
- FFAPQAZWUVSBCM-UHFFFAOYSA-N 7-chloro-3-(3-fluorophenyl)-n,n,5-trimethyl-4-oxopyridazino[4,5-b]indole-1-carboxamide Chemical compound O=C1C=2N(C)C3=CC(Cl)=CC=C3C=2C(C(=O)N(C)C)=NN1C1=CC=CC(F)=C1 FFAPQAZWUVSBCM-UHFFFAOYSA-N 0.000 description 2
- IEVSHILPTOJQFZ-UHFFFAOYSA-N 7-chloro-n,n,5-trimethyl-4-oxo-3-phenylpyridazino[4,5-b]indole-1-carboxamide Chemical compound O=C1C=2N(C)C3=CC(Cl)=CC=C3C=2C(C(=O)N(C)C)=NN1C1=CC=CC=C1 IEVSHILPTOJQFZ-UHFFFAOYSA-N 0.000 description 2
- HUDBDWIQSIGUDI-UHFFFAOYSA-N Ethyl 3-indoleacetate Chemical compound C1=CC=C2C(CC(=O)OCC)=CNC2=C1 HUDBDWIQSIGUDI-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 229940049706 benzodiazepine Drugs 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 2
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- QMVJTCIUKISOGR-UHFFFAOYSA-N ethyl 6-chloro-1-methylindole-2-carboxylate Chemical compound C1=C(Cl)C=C2N(C)C(C(=O)OCC)=CC2=C1 QMVJTCIUKISOGR-UHFFFAOYSA-N 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical group NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 2
- 229940067157 phenylhydrazine Drugs 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 2
- CRRIAWUJYMLJOE-UHFFFAOYSA-N (3-chlorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=CC(Cl)=C1 CRRIAWUJYMLJOE-UHFFFAOYSA-N 0.000 description 1
- SKVGLOFWEJFQKU-UHFFFAOYSA-N (3-fluorophenyl)hydrazine;hydron;chloride Chemical compound Cl.NNC1=CC=CC(F)=C1 SKVGLOFWEJFQKU-UHFFFAOYSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- MANJIGKYCYWWBD-UHFFFAOYSA-N 2-chloro-2-oxoacetic acid Chemical compound OC(=O)C(Cl)=O MANJIGKYCYWWBD-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- BKPSJOSKWKTWAG-UHFFFAOYSA-N 6-chloro-1h-indole-2-carboxylic acid Chemical class C1=C(Cl)C=C2NC(C(=O)O)=CC2=C1 BKPSJOSKWKTWAG-UHFFFAOYSA-N 0.000 description 1
- QPPVZPAYYSTDAN-UHFFFAOYSA-N 7-chloro-3-(3-chlorophenyl)-n,n,5-trimethyl-4-oxopyridazino[4,5-b]indole-1-carboxamide Chemical compound O=C1C=2N(C)C3=CC(Cl)=CC=C3C=2C(C(=O)N(C)C)=NN1C1=CC=CC(Cl)=C1 QPPVZPAYYSTDAN-UHFFFAOYSA-N 0.000 description 1
- HJRLVCHTLOOVRV-UHFFFAOYSA-N 7-chloro-n,n-diethyl-3-(3-methoxyphenyl)-5-methyl-4-oxopyridazino[4,5-b]indole-1-carboxamide Chemical compound O=C1C=2N(C)C3=CC(Cl)=CC=C3C=2C(C(=O)N(CC)CC)=NN1C1=CC=CC(OC)=C1 HJRLVCHTLOOVRV-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 208000021401 Facial Nerve injury Diseases 0.000 description 1
- 208000033463 Ischaemic neuropathy Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 240000003768 Solanum lycopersicum Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- OWZFULPEVHKEKS-UHFFFAOYSA-N ethyl 2-chloro-2-oxoacetate Chemical compound CCOC(=O)C(Cl)=O OWZFULPEVHKEKS-UHFFFAOYSA-N 0.000 description 1
- PEYVMWBTZRUKBN-UHFFFAOYSA-N ethyl 7-chloro-3-(3-fluorophenyl)-5-methyl-4-oxopyridazino[4,5-b]indole-1-carboxylate Chemical compound O=C1C=2N(C)C3=CC(Cl)=CC=C3C=2C(C(=O)OCC)=NN1C1=CC=CC(F)=C1 PEYVMWBTZRUKBN-UHFFFAOYSA-N 0.000 description 1
- OZXKUHMJKZOWAA-UHFFFAOYSA-N ethyl 7-chloro-3-(3-methoxyphenyl)-5-methyl-4-oxopyridazino[4,5-b]indole-1-carboxylate Chemical compound O=C1C=2N(C)C3=CC(Cl)=CC=C3C=2C(C(=O)OCC)=NN1C1=CC=CC(OC)=C1 OZXKUHMJKZOWAA-UHFFFAOYSA-N 0.000 description 1
- JJCGYLAKDUJYLK-UHFFFAOYSA-N ethyl 7-chloro-5-methyl-4-oxo-3-phenylpyridazino[4,5-b]indole-1-carboxylate Chemical compound O=C1C=2N(C)C3=CC(Cl)=CC=C3C=2C(C(=O)OCC)=NN1C1=CC=CC=C1 JJCGYLAKDUJYLK-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- -1 for example Chemical class 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 239000011539 homogenization buffer Substances 0.000 description 1
- GMXFZBZOVZOYNQ-UHFFFAOYSA-N hydron;(3-methoxyphenyl)hydrazine;chloride Chemical compound Cl.COC1=CC=CC(NN)=C1 GMXFZBZOVZOYNQ-UHFFFAOYSA-N 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- CQILOHWHIWNQOE-UHFFFAOYSA-N indole-1-carboxamide Chemical compound C1=CC=C2N(C(=O)N)C=CC2=C1 CQILOHWHIWNQOE-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000002320 spinal muscular atrophy Diseases 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000003511 tertiary amides Chemical class 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9900805A FR2788776B1 (fr) | 1999-01-26 | 1999-01-26 | Derives de 4-oxo-3, 5-dihydro-4h-pyridazino [4,5-b] indole-1 -carboxamide, leur preparation et leur application en therapeutique |
| FR99/00805 | 1999-01-26 | ||
| PCT/FR2000/000134 WO2000044751A1 (fr) | 1999-01-26 | 2000-01-21 | DERIVES DE 4-OXO-3,5-DIHYDRO-4H-PYRIDAZINO[4,5-b]INDOLE-1-CARBOXAMIDE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002535406A JP2002535406A (ja) | 2002-10-22 |
| JP2002535406A5 JP2002535406A5 (https=) | 2007-03-22 |
| JP4574860B2 true JP4574860B2 (ja) | 2010-11-04 |
Family
ID=9541211
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000596007A Expired - Fee Related JP4574860B2 (ja) | 1999-01-26 | 2000-01-21 | ４−オキソ−３，５−ジヒドロ−４Ｈ−ピリダジノ［４，５−ｂ］インドール−１−カルボキサミド誘導体、それらの製造、および治療におけるそれらの適用 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US6451795B1 (https=) |
| EP (1) | EP1149101B1 (https=) |
| JP (1) | JP4574860B2 (https=) |
| AR (1) | AR030016A1 (https=) |
| AT (1) | ATE236905T1 (https=) |
| AU (1) | AU3057800A (https=) |
| CO (1) | CO5160255A1 (https=) |
| DE (1) | DE60002043T2 (https=) |
| ES (1) | ES2194696T3 (https=) |
| FR (1) | FR2788776B1 (https=) |
| WO (1) | WO2000044751A1 (https=) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2788696B1 (fr) * | 1999-01-26 | 2004-03-05 | Synthelabo | Utilisation de derives de pyridazino [4,5-b] indole-1-acetamide pour la preparation de medicaments destines aux maladies du systeme nerveux central |
| FR2811990A1 (fr) * | 2000-07-24 | 2002-01-25 | Sanofi Synthelabo | DERIVES DE 1-(4-OXO-3,5-DIHYDRO-4H-PYRIDAZINO[4,5-b]INDOLE-1 -CARBONYL)PIPERAZINE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
| FR2833953B1 (fr) * | 2001-12-21 | 2004-12-03 | Sanofi Synthelabo | DERIVES DE 3-HETEROARYL-3,5-DIHYDRO-4-OXO-4H-PYRIDAZINO [4,5-b]INDOLE-1-CARBOXAMIDE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE |
| FR2838124B1 (fr) * | 2002-04-03 | 2004-05-28 | Sanofi Synthelabo | Derives de 3-heteroaryl-3,5-dihydro-4-oxo-4h-pyridazino [4,5-b]indole-1-acetamide, leur preparation et leur application en therapeutique |
| GB0523506D0 (en) * | 2005-11-18 | 2005-12-28 | Hammersmith Imanet Ltd | Novel in vivo imaging compounds |
| GB0818738D0 (en) * | 2008-10-13 | 2008-11-19 | Ge Healthcare Ltd | Imaging neuroflammation |
| GB0905328D0 (en) * | 2009-03-27 | 2009-05-13 | Ge Healthcare Ltd | Indole derivatives |
| EP2552891B1 (en) * | 2010-03-26 | 2018-08-08 | GE Healthcare Limited | Tricyclic indole derivatives as pbr ligands |
| US9220795B2 (en) | 2011-09-22 | 2015-12-29 | Ge Healthcare Limited | Indole derivatives |
| GB201312768D0 (en) * | 2013-07-17 | 2013-08-28 | Ge Healthcare Ltd | Work-up procedure |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9109972D0 (en) * | 1991-05-09 | 1991-07-03 | Ici Plc | Therapeutic compounds |
| GB9411955D0 (en) * | 1994-06-15 | 1994-08-03 | Merck Sharp & Dohme | Therapeutic agents |
| FR2754262B1 (fr) * | 1996-10-08 | 1998-10-30 | Synthelabo | Derives de 1h-pyrido[3,4-b]indole-4-carboxamide, leur preparation et leur application en therapeutique |
| FR2766823B1 (fr) | 1997-07-30 | 1999-10-08 | Synthelabo | Derives de 4-oxo-3,5-dihydro-4h-pyridazino[4,5-b] indole-1-acetamide, leur preparation et leur application en therapeutique |
-
1999
- 1999-01-26 FR FR9900805A patent/FR2788776B1/fr not_active Expired - Fee Related
-
2000
- 2000-01-21 ES ES00900636T patent/ES2194696T3/es not_active Expired - Lifetime
- 2000-01-21 JP JP2000596007A patent/JP4574860B2/ja not_active Expired - Fee Related
- 2000-01-21 AT AT00900636T patent/ATE236905T1/de active
- 2000-01-21 WO PCT/FR2000/000134 patent/WO2000044751A1/fr not_active Ceased
- 2000-01-21 US US09/889,984 patent/US6451795B1/en not_active Expired - Fee Related
- 2000-01-21 DE DE60002043T patent/DE60002043T2/de not_active Expired - Lifetime
- 2000-01-21 EP EP00900636A patent/EP1149101B1/fr not_active Expired - Lifetime
- 2000-01-21 AU AU30578/00A patent/AU3057800A/en not_active Abandoned
- 2000-01-25 CO CO00003864A patent/CO5160255A1/es unknown
- 2000-01-25 AR ARP000100304A patent/AR030016A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CO5160255A1 (es) | 2002-05-30 |
| AU3057800A (en) | 2000-08-18 |
| ATE236905T1 (de) | 2003-04-15 |
| JP2002535406A (ja) | 2002-10-22 |
| ES2194696T3 (es) | 2003-12-01 |
| WO2000044751A1 (fr) | 2000-08-03 |
| EP1149101B1 (fr) | 2003-04-09 |
| EP1149101A1 (fr) | 2001-10-31 |
| DE60002043D1 (de) | 2003-05-15 |
| FR2788776B1 (fr) | 2001-02-23 |
| FR2788776A1 (fr) | 2000-07-28 |
| AR030016A1 (es) | 2003-08-13 |
| US6451795B1 (en) | 2002-09-17 |
| DE60002043T2 (de) | 2004-02-19 |
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