JP2002535408A - ピラジノ（アザ）インドール誘導体 - Google Patents
ピラジノ（アザ）インドール誘導体Info
- Publication number
- JP2002535408A JP2002535408A JP2000596009A JP2000596009A JP2002535408A JP 2002535408 A JP2002535408 A JP 2002535408A JP 2000596009 A JP2000596009 A JP 2000596009A JP 2000596009 A JP2000596009 A JP 2000596009A JP 2002535408 A JP2002535408 A JP 2002535408A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- hydrogen
- indole
- chloro
- mmol
- 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.)
- Pending
Links
- 229940054051 antipsychotic indole derivative Drugs 0.000 title description 2
- 150000002475 indoles Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 129
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- 238000011282 treatment Methods 0.000 claims abstract description 18
- 208000035475 disorder Diseases 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 8
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 6
- 239000000651 prodrug Substances 0.000 claims abstract description 5
- 229940002612 prodrug Drugs 0.000 claims abstract description 5
- 208000018522 Gastrointestinal disease Diseases 0.000 claims abstract description 4
- 230000006378 damage Effects 0.000 claims abstract description 4
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 claims abstract description 3
- 201000010064 diabetes insipidus Diseases 0.000 claims abstract description 3
- 201000002859 sleep apnea Diseases 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 89
- 239000001257 hydrogen Substances 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 56
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 21
- 208000008589 Obesity Diseases 0.000 claims description 18
- 235000020824 obesity Nutrition 0.000 claims description 18
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 17
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 8
- 125000004104 aryloxy group Chemical group 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 238000011321 prophylaxis Methods 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000003542 behavioural effect Effects 0.000 claims description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 208000015114 central nervous system disease Diseases 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- UONHLVCQYSKINY-UHFFFAOYSA-N 7-chloro-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1NCCN2C3=CC(Cl)=CC=C3CC21 UONHLVCQYSKINY-UHFFFAOYSA-N 0.000 claims description 4
- YNABRINHPQKTRU-UHFFFAOYSA-N 7-chloro-8-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1C2CNCCN2C2=C1C=C(C)C(Cl)=C2 YNABRINHPQKTRU-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- KRZJRNZICWNMOA-GXSJLCMTSA-N (3s,4r)-4,8-dihydroxy-3-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=CC=C2[C@@H](O)[C@@H](OC)CC(=O)C2=C1O KRZJRNZICWNMOA-GXSJLCMTSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 230000009429 distress Effects 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 230000002458 infectious effect Effects 0.000 claims description 3
- 231100000331 toxic Toxicity 0.000 claims description 3
- 230000002588 toxic effect Effects 0.000 claims description 3
- RQMCYUIGJSZWDQ-SNVBAGLBSA-N (10aR)-8-chloro-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1CNC[C@H]2CC3=CC(Cl)=CC=C3N21 RQMCYUIGJSZWDQ-SNVBAGLBSA-N 0.000 claims description 2
- UONHLVCQYSKINY-SNVBAGLBSA-N (10ar)-7-chloro-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1NCCN2C3=CC(Cl)=CC=C3C[C@@H]21 UONHLVCQYSKINY-SNVBAGLBSA-N 0.000 claims description 2
- ILABBYCXAZPSHM-UHFFFAOYSA-N 7-bromo-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1NCCN2C3=CC(Br)=CC=C3CC21 ILABBYCXAZPSHM-UHFFFAOYSA-N 0.000 claims description 2
- MSHHWMXRKJPFII-UHFFFAOYSA-N 8-chloro-2-methyl-3,4,10,10a-tetrahydro-1h-pyrazino[1,2-a]indole Chemical compound ClC1=CC=C2N3CCN(C)CC3CC2=C1 MSHHWMXRKJPFII-UHFFFAOYSA-N 0.000 claims description 2
- 208000007848 Alcoholism Diseases 0.000 claims description 2
- 208000019901 Anxiety disease Diseases 0.000 claims description 2
- 208000020925 Bipolar disease Diseases 0.000 claims description 2
- 208000032841 Bulimia Diseases 0.000 claims description 2
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 206010049119 Emotional distress Diseases 0.000 claims description 2
- 206010022773 Intracranial pressure increased Diseases 0.000 claims description 2
- 201000009906 Meningitis Diseases 0.000 claims description 2
- 208000019695 Migraine disease Diseases 0.000 claims description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 2
- 208000028017 Psychotic disease Diseases 0.000 claims description 2
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- 230000016571 aggressive behavior Effects 0.000 claims description 2
- 201000007930 alcohol dependence Diseases 0.000 claims description 2
- 208000025748 atypical depressive disease Diseases 0.000 claims description 2
- 230000007812 deficiency Effects 0.000 claims description 2
- 208000010643 digestive system disease Diseases 0.000 claims description 2
- 206010013663 drug dependence Diseases 0.000 claims description 2
- 206010014599 encephalitis Diseases 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 230000005176 gastrointestinal motility Effects 0.000 claims description 2
- 208000018685 gastrointestinal system disease Diseases 0.000 claims description 2
- 208000014674 injury Diseases 0.000 claims description 2
- 206010027599 migraine Diseases 0.000 claims description 2
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 208000022821 personality disease Diseases 0.000 claims description 2
- 208000020016 psychiatric disease Diseases 0.000 claims description 2
- 201000000980 schizophrenia Diseases 0.000 claims description 2
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 208000011117 substance-related disease Diseases 0.000 claims description 2
- 230000008733 trauma Effects 0.000 claims description 2
- 208000000103 Anorexia Nervosa Diseases 0.000 claims 1
- 206010006550 Bulimia nervosa Diseases 0.000 claims 1
- 208000007536 Thrombosis Diseases 0.000 claims 1
- 206010027175 memory impairment Diseases 0.000 claims 1
- 208000020685 sleep-wake disease Diseases 0.000 claims 1
- 239000003446 ligand Substances 0.000 abstract description 6
- 239000000018 receptor agonist Substances 0.000 abstract description 5
- 229940044601 receptor agonist Drugs 0.000 abstract description 5
- 230000003579 anti-obesity Effects 0.000 abstract description 3
- 230000009471 action Effects 0.000 abstract description 2
- 239000000883 anti-obesity agent Substances 0.000 abstract 1
- 229940125710 antiobesity agent Drugs 0.000 abstract 1
- 230000002526 effect on cardiovascular system Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 132
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 110
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 74
- 239000000243 solution Substances 0.000 description 71
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 239000007787 solid Substances 0.000 description 54
- 239000003921 oil Substances 0.000 description 48
- 235000019198 oils Nutrition 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 46
- -1 carboxy, carboxy Chemical group 0.000 description 44
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 37
- 235000019341 magnesium sulphate Nutrition 0.000 description 37
- 239000002904 solvent Substances 0.000 description 35
- 239000000284 extract Substances 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- 239000012267 brine Substances 0.000 description 31
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 31
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 229910004298 SiO 2 Inorganic materials 0.000 description 29
- 238000003818 flash chromatography Methods 0.000 description 28
- 239000000047 product Substances 0.000 description 28
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000010992 reflux Methods 0.000 description 23
- 229920006395 saturated elastomer Polymers 0.000 description 22
- 239000000725 suspension Substances 0.000 description 22
- 239000010410 layer Substances 0.000 description 20
- 108020003175 receptors Proteins 0.000 description 20
- 102000005962 receptors Human genes 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- RDYSIKZETQMYPK-UHFFFAOYSA-N azanium;ethyl acetate;methanol;hydroxide Chemical compound N.O.OC.CCOC(C)=O RDYSIKZETQMYPK-UHFFFAOYSA-N 0.000 description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 15
- 239000010779 crude oil Substances 0.000 description 14
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 14
- 239000012230 colorless oil Substances 0.000 description 12
- 239000012065 filter cake Substances 0.000 description 12
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 12
- 238000003756 stirring Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 10
- ZMDYEAGYESBOJZ-UHFFFAOYSA-N ethanamine;1h-indole Chemical compound CCN.C1=CC=C2NC=CC2=C1 ZMDYEAGYESBOJZ-UHFFFAOYSA-N 0.000 description 9
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- AEIDURNZWCNQIM-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrazino[1,2-a]indole Chemical compound C1=CC=C2N3CCNCC3=CC2=C1 AEIDURNZWCNQIM-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000003638 chemical reducing agent Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 239000012280 lithium aluminium hydride Substances 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 7
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 238000000354 decomposition reaction Methods 0.000 description 7
- 235000012631 food intake Nutrition 0.000 description 7
- 239000001530 fumaric acid Substances 0.000 description 7
- 235000011087 fumaric acid Nutrition 0.000 description 7
- 125000001188 haloalkyl group Chemical group 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 6
- 239000005695 Ammonium acetate Substances 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
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- 229940043376 ammonium acetate Drugs 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000003710 aryl alkyl group Chemical group 0.000 description 5
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 5
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- 239000012044 organic layer Substances 0.000 description 5
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- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 5
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 125000002015 acyclic group Chemical group 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 239000010502 orange oil Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
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Classifications
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- 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
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- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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Landscapes
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- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Silver Salt Photography Or Processing Solution Therefor (AREA)
- Apparatus For Disinfection Or Sterilisation (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9902047.1 | 1999-01-29 | ||
| GBGB9902047.1A GB9902047D0 (en) | 1999-01-29 | 1999-01-29 | Chemical compounds XI |
| PCT/GB2000/000244 WO2000044753A1 (en) | 1999-01-29 | 2000-01-28 | Pirazino(aza)indole derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002535408A true JP2002535408A (ja) | 2002-10-22 |
| JP2002535408A5 JP2002535408A5 (enExample) | 2007-03-08 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000596009A Pending JP2002535408A (ja) | 1999-01-29 | 2000-01-28 | ピラジノ（アザ）インドール誘導体 |
Country Status (18)
| Country | Link |
|---|---|
| US (4) | US6800627B1 (enExample) |
| EP (1) | EP1147110B1 (enExample) |
| JP (1) | JP2002535408A (enExample) |
| KR (1) | KR100633375B1 (enExample) |
| CN (2) | CN100418968C (enExample) |
| AT (1) | ATE239731T1 (enExample) |
| AU (1) | AU758685B2 (enExample) |
| BR (1) | BR0008979A (enExample) |
| CA (1) | CA2359034A1 (enExample) |
| DE (1) | DE60002554T2 (enExample) |
| DK (1) | DK1147110T3 (enExample) |
| ES (1) | ES2199132T3 (enExample) |
| GB (1) | GB9902047D0 (enExample) |
| MX (1) | MXPA01007643A (enExample) |
| PT (1) | PT1147110E (enExample) |
| TR (1) | TR200102161T2 (enExample) |
| WO (1) | WO2000044753A1 (enExample) |
| ZA (1) | ZA200106202B (enExample) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006528702A (ja) * | 2003-05-21 | 2006-12-21 | プロシディオン・リミテッド | グリコーゲンホスホリラーゼのピロロピリジン−２−カルボン酸アミドインヒビター |
| JP2008540368A (ja) * | 2005-05-03 | 2008-11-20 | エフ．ホフマン−ラ ロシュ アーゲー | ５−ｈｔ２リガンドとしての四環式アザピラジノインドリン |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6960579B1 (en) | 1998-05-19 | 2005-11-01 | Alcon Manufacturing, Ltd. | Serotonergic 5HT7 receptor compounds for treating ocular and CNS disorders |
| FR2799757B1 (fr) * | 1999-10-15 | 2001-12-14 | Adir | Nouveaux derives polycycliques azaindoliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| WO2002010169A1 (en) * | 2000-07-31 | 2002-02-07 | F. Hoffmann-La Roche Ag | Piperazine derivatives |
| SE0004245D0 (sv) | 2000-11-20 | 2000-11-20 | Pharmacia Ab | Novel compounds and their use |
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| GB9819019D0 (en) * | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds II |
| GB9819035D0 (en) * | 1998-09-01 | 1998-10-28 | Cerebrus Res Ltd | Chemical compounds VII |
| GB9819033D0 (en) * | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds VI |
| GB9918962D0 (en) * | 1999-08-11 | 1999-10-13 | Cerebrus Ltd | Chemical compounds xxii |
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1999
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2000
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- 2000-01-28 AU AU21196/00A patent/AU758685B2/en not_active Ceased
- 2000-01-28 CA CA002359034A patent/CA2359034A1/en not_active Abandoned
- 2000-01-28 WO PCT/GB2000/000244 patent/WO2000044753A1/en not_active Ceased
- 2000-01-28 JP JP2000596009A patent/JP2002535408A/ja active Pending
- 2000-01-28 TR TR2001/02161T patent/TR200102161T2/xx unknown
- 2000-01-28 BR BR0008979-6A patent/BR0008979A/pt not_active Application Discontinuation
- 2000-01-28 KR KR1020017009583A patent/KR100633375B1/ko not_active Expired - Fee Related
- 2000-01-28 EP EP00901240A patent/EP1147110B1/en not_active Expired - Lifetime
- 2000-01-28 US US09/890,186 patent/US6800627B1/en not_active Expired - Fee Related
- 2000-01-28 DK DK00901240T patent/DK1147110T3/da active
- 2000-01-28 ES ES00901240T patent/ES2199132T3/es not_active Expired - Lifetime
- 2000-01-28 MX MXPA01007643A patent/MXPA01007643A/es not_active IP Right Cessation
- 2000-01-28 CN CNB2006100710947A patent/CN100418968C/zh not_active Expired - Fee Related
- 2000-01-28 AT AT00901240T patent/ATE239731T1/de not_active IP Right Cessation
- 2000-01-28 CN CNB008031398A patent/CN1289499C/zh not_active Expired - Fee Related
- 2000-01-28 PT PT00901240T patent/PT1147110E/pt unknown
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2001
- 2001-07-27 ZA ZA200106202A patent/ZA200106202B/en unknown
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2003
- 2003-08-05 US US10/633,532 patent/US20040039200A1/en not_active Abandoned
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- 2006-03-14 US US11/374,157 patent/US20060160816A1/en not_active Abandoned
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| JPH0641132A (ja) * | 1992-06-05 | 1994-02-15 | F Hoffmann La Roche Ag | ピラジノインドール類 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006528702A (ja) * | 2003-05-21 | 2006-12-21 | プロシディオン・リミテッド | グリコーゲンホスホリラーゼのピロロピリジン−２−カルボン酸アミドインヒビター |
| JP2011252005A (ja) * | 2003-05-21 | 2011-12-15 | Prosidion Ltd | グリコーゲンホスホリラーゼのピロロピリジン−２−カルボン酸アミドインヒビター |
| JP2008540368A (ja) * | 2005-05-03 | 2008-11-20 | エフ．ホフマン−ラ ロシュ アーゲー | ５−ｈｔ２リガンドとしての四環式アザピラジノインドリン |
Also Published As
| Publication number | Publication date |
|---|---|
| DE60002554D1 (de) | 2003-06-12 |
| CN100418968C (zh) | 2008-09-17 |
| KR20010101873A (ko) | 2001-11-15 |
| AU758685B2 (en) | 2003-03-27 |
| CN1289499C (zh) | 2006-12-13 |
| EP1147110A1 (en) | 2001-10-24 |
| WO2000044753A1 (en) | 2000-08-03 |
| AU2119600A (en) | 2000-08-18 |
| DK1147110T3 (da) | 2003-09-01 |
| US20060160816A1 (en) | 2006-07-20 |
| CA2359034A1 (en) | 2000-08-03 |
| PT1147110E (pt) | 2003-09-30 |
| EP1147110B1 (en) | 2003-05-07 |
| US6800627B1 (en) | 2004-10-05 |
| CN1337963A (zh) | 2002-02-27 |
| ZA200106202B (en) | 2002-07-29 |
| ES2199132T3 (es) | 2004-02-16 |
| KR100633375B1 (ko) | 2006-10-16 |
| MXPA01007643A (es) | 2003-06-24 |
| DE60002554T2 (de) | 2004-03-25 |
| US20040039200A1 (en) | 2004-02-26 |
| US20040092525A1 (en) | 2004-05-13 |
| BR0008979A (pt) | 2002-02-05 |
| TR200102161T2 (tr) | 2002-05-21 |
| US7145009B2 (en) | 2006-12-05 |
| CN1837207A (zh) | 2006-09-27 |
| ATE239731T1 (de) | 2003-05-15 |
| GB9902047D0 (en) | 1999-03-17 |
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