NO310026B1 - 8-substituerte-1,3,8-triaza-spiro[4,5]dekan-4-on-derivater - Google Patents

8-substituerte-1,3,8-triaza-spiro[4,5]dekan-4-on-derivater Download PDF

Info

Publication number: NO310026B1
Authority: NO; Norway
Prior art keywords: phenyl; triazaspiro; decan; tetrahydro; lower alkyl
Prior art date: 1997-01-30

Application number

NO980332A

Other languages

English (en)

Norwegian (no)

Other versions

NO980332L (no

NO980332D0 (no

Inventor

Geo Adam

Andrea Cesura

Guido Galley

Francois Jenck

Jr Frederick Monsma

Stephan Roever

Juergen Wichmann

Original Assignee

Hoffmann La Roche

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-01-30

Filing date

1998-01-26

Publication date

2001-05-07

1998-01-26 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1998-01-26 Publication of NO980332D0 publication Critical patent/NO980332D0/no

1998-07-31 Publication of NO980332L publication Critical patent/NO980332L/no

2001-05-07 Publication of NO310026B1 publication Critical patent/NO310026B1/no

Links

-1 8-substituted-1,3,8-triazaspiro [4,5] decan-4-one Chemical class 0.000 title claims description 9
150000001875 compounds Chemical class 0.000 claims description 148
125000000217 alkyl group Chemical group 0.000 claims description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 26
150000003839 salts Chemical class 0.000 claims description 18
108090000622 Nociceptin Proteins 0.000 claims description 14
PULGYDLMFSFVBL-SMFNREODSA-N nociceptin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)[C@@H](C)O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 PULGYDLMFSFVBL-SMFNREODSA-N 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
208000002193 Pain Diseases 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
229920006395 saturated elastomer Polymers 0.000 claims description 6
239000002253 acid Substances 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
208000024827 Alzheimer disease Diseases 0.000 claims description 4
208000000044 Amnesia Diseases 0.000 claims description 4
208000027796 Blood pressure disease Diseases 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
208000000094 Chronic Pain Diseases 0.000 claims description 4
206010010904 Convulsion Diseases 0.000 claims description 4
206010012289 Dementia Diseases 0.000 claims description 4
206010013654 Drug abuse Diseases 0.000 claims description 4
208000030814 Eating disease Diseases 0.000 claims description 4
208000019454 Feeding and Eating disease Diseases 0.000 claims description 4
208000026139 Memory disease Diseases 0.000 claims description 4
208000013200 Stress disease Diseases 0.000 claims description 4
208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 4
230000001154 acute effect Effects 0.000 claims description 4
208000005298 acute pain Diseases 0.000 claims description 4
230000004872 arterial blood pressure Effects 0.000 claims description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
239000000460 chlorine Substances 0.000 claims description 4
230000036461 convulsion Effects 0.000 claims description 4
235000014632 disordered eating Nutrition 0.000 claims description 4
229940079593 drug Drugs 0.000 claims description 4
206010015037 epilepsy Diseases 0.000 claims description 4
230000029142 excretion Effects 0.000 claims description 4
208000014674 injury Diseases 0.000 claims description 4
230000006984 memory degeneration Effects 0.000 claims description 4
208000023060 memory loss Diseases 0.000 claims description 4
230000000926 neurological effect Effects 0.000 claims description 4
208000011117 substance-related disease Diseases 0.000 claims description 4
230000008733 trauma Effects 0.000 claims description 4
208000019901 Anxiety disease Diseases 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000003545 alkoxy group Chemical group 0.000 claims description 3
230000036506 anxiety Effects 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
230000001225 therapeutic effect Effects 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
102000048266 Nociceptin Human genes 0.000 claims 4
150000002431 hydrogen Chemical class 0.000 claims 3
208000008589 Obesity Diseases 0.000 claims 2
235000020824 obesity Nutrition 0.000 claims 2
FQJXOOHCZZQVHD-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CN(C2C3=CC=CC=C3CC2)CCC11C(=O)NCN1C1=CC=CC=C1 FQJXOOHCZZQVHD-UHFFFAOYSA-N 0.000 claims 1
PYQRZQXALHGAGL-UHFFFAOYSA-N 8-(5-methyl-1,2,3,4-tetrahydronaphthalen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CCC=2C(C)=CC=CC=2C1N(CC1)CCC1(C(NC1)=O)N1C1=CC=CC=C1 PYQRZQXALHGAGL-UHFFFAOYSA-N 0.000 claims 1
238000000034 method Methods 0.000 description 100
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
HTQWGIHCFPWKAS-UHFFFAOYSA-N 1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CNCCC11C(=O)NCN1C1=CC=CC=C1 HTQWGIHCFPWKAS-UHFFFAOYSA-N 0.000 description 41
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
239000000203 mixture Substances 0.000 description 36
239000007787 solid Substances 0.000 description 32
239000000243 solution Substances 0.000 description 22
239000012074 organic phase Substances 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
MCXBIZXYNQHVCM-UHFFFAOYSA-N decan-4-one;hydrochloride Chemical compound Cl.CCCCCCC(=O)CCC MCXBIZXYNQHVCM-UHFFFAOYSA-N 0.000 description 12
102400001111 Nociceptin Human genes 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
239000000543 intermediate Substances 0.000 description 10
239000003921 oil Substances 0.000 description 10
235000019198 oils Nutrition 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
150000001408 amides Chemical class 0.000 description 9
238000002955 isolation Methods 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
235000011152 sodium sulphate Nutrition 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 8
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
GKBLBGBXCLKVGY-UHFFFAOYSA-N 8-(5,8-dichloro-1,2,3,4-tetrahydronaphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CC=2C(Cl)=CC=C(Cl)C=2CC1N(CC1)CCC1(C(NC1)=O)N1C1=CC=CC=C1 GKBLBGBXCLKVGY-UHFFFAOYSA-N 0.000 description 7
239000000047 product Substances 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
239000006260 foam Substances 0.000 description 6
239000012442 inert solvent Substances 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000000829 suppository Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
239000002808 molecular sieve Substances 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
QBTZALYOZZYCLX-UHFFFAOYSA-N 1-(1,2-dihydroacenaphthylen-1-yl)piperidin-4-one Chemical compound C1CC(=O)CCN1C(C1)C2=C3C1=CC=CC3=CC=C2 QBTZALYOZZYCLX-UHFFFAOYSA-N 0.000 description 4
PIDODLRGSKHQDP-UHFFFAOYSA-M 1-ethyl-1-methylpiperidin-1-ium-4-one;iodide Chemical compound [I-].CC[N+]1(C)CCC(=O)CC1 PIDODLRGSKHQDP-UHFFFAOYSA-M 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
239000000872 buffer Substances 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
MKJDUHZPLQYUCB-UHFFFAOYSA-N decan-4-one Chemical compound CCCCCCC(=O)CCC MKJDUHZPLQYUCB-UHFFFAOYSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
108010020615 nociceptin receptor Proteins 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000000725 suspension Substances 0.000 description 4
QWKMIJLSWJYLDZ-AWEZNQCLSA-N 1-[(1s)-2,3-dihydro-1h-inden-1-yl]piperidin-4-one Chemical compound C1CC(=O)CCN1[C@@H]1C2=CC=CC=C2CC1 QWKMIJLSWJYLDZ-AWEZNQCLSA-N 0.000 description 3
PJYIGONWNQJLJK-UHFFFAOYSA-N 2,3-dihydro-1h-phenalen-1-amine Chemical compound C1=CC(C(N)CC2)=C3C2=CC=CC3=C1 PJYIGONWNQJLJK-UHFFFAOYSA-N 0.000 description 3
PBIUDEUWYGBHDW-UHFFFAOYSA-N 2-chloro-1-pyridin-3-ylethanone;hydrochloride Chemical compound Cl.ClCC(=O)C1=CC=CN=C1 PBIUDEUWYGBHDW-UHFFFAOYSA-N 0.000 description 3
DJQXETLAJQPHFD-UHFFFAOYSA-N 8-(8-chloro-1,2,3,4-tetrahydronaphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride Chemical compound Cl.C1C=2C(Cl)=CC=CC=2CCC1N(CC1)CCC1(C(NC1)=O)N1C1=CC=CC=C1 DJQXETLAJQPHFD-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
239000000556 agonist Substances 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
229910021529 ammonia Inorganic materials 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
235000009508 confectionery Nutrition 0.000 description 3
239000002274 desiccant Substances 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000007429 general method Methods 0.000 description 3
150000003840 hydrochlorides Chemical class 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
150000002576 ketones Chemical class 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000012528 membrane Substances 0.000 description 3
239000000825 pharmaceutical preparation Substances 0.000 description 3
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
239000011734 sodium Substances 0.000 description 3
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 3
239000001993 wax Substances 0.000 description 3
LCYNDXQWJAMEAI-LLVKDONJSA-N (1r)-1,2-dihydroacenaphthylen-1-amine Chemical compound C1=CC([C@H](N)C2)=C3C2=CC=CC3=C1 LCYNDXQWJAMEAI-LLVKDONJSA-N 0.000 description 2
LCYNDXQWJAMEAI-NSHDSACASA-N (1s)-1,2-dihydroacenaphthylen-1-amine Chemical compound C1=CC([C@@H](N)C2)=C3C2=CC=CC3=C1 LCYNDXQWJAMEAI-NSHDSACASA-N 0.000 description 2
LBHGMYPYADADJC-UHFFFAOYSA-N 1-(9h-fluoren-9-yl)piperidin-4-one Chemical compound C1CC(=O)CCN1C1C2=CC=CC=C2C2=CC=CC=C21 LBHGMYPYADADJC-UHFFFAOYSA-N 0.000 description 2
QBTZALYOZZYCLX-MRXNPFEDSA-N 1-[(1r)-1,2-dihydroacenaphthylen-1-yl]piperidin-4-one Chemical compound C1CC(=O)CCN1[C@H](C1)C2=C3C1=CC=CC3=CC=C2 QBTZALYOZZYCLX-MRXNPFEDSA-N 0.000 description 2
QWKMIJLSWJYLDZ-CQSZACIVSA-N 1-[(1r)-2,3-dihydro-1h-inden-1-yl]piperidin-4-one Chemical compound C1CC(=O)CCN1[C@H]1C2=CC=CC=C2CC1 QWKMIJLSWJYLDZ-CQSZACIVSA-N 0.000 description 2
QBTZALYOZZYCLX-INIZCTEOSA-N 1-[(1s)-1,2-dihydroacenaphthylen-1-yl]piperidin-4-one Chemical compound C1CC(=O)CCN1[C@@H](C1)C2=C3C1=CC=CC3=CC=C2 QBTZALYOZZYCLX-INIZCTEOSA-N 0.000 description 2
AFEYDTWTTFRCSH-UHFFFAOYSA-N 1-naphthalen-1-ylnaphthalene;phosphoric acid Chemical compound OP(O)(O)=O.C1=CC=C2C(C=3C4=CC=CC=C4C=CC=3)=CC=CC2=C1 AFEYDTWTTFRCSH-UHFFFAOYSA-N 0.000 description 2
JYDZOIFXAFDTNB-UHFFFAOYSA-N 1-phenyl-8-(1,2,3,4-tetrahydronaphthalen-2-yl)-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride Chemical compound Cl.C1CN(C2CC3=CC=CC=C3CC2)CCC11C(=O)NCN1C1=CC=CC=C1 JYDZOIFXAFDTNB-UHFFFAOYSA-N 0.000 description 2
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
XVTQSYKCADSUHN-UHFFFAOYSA-N 3-methyl-2,3-dihydroinden-1-one Chemical compound C1=CC=C2C(C)CC(=O)C2=C1 XVTQSYKCADSUHN-UHFFFAOYSA-N 0.000 description 2
JJYPMNFTHPTTDI-UHFFFAOYSA-N 3-methylaniline Chemical compound CC1=CC=CC(N)=C1 JJYPMNFTHPTTDI-UHFFFAOYSA-N 0.000 description 2
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 2
RUORWXQKVXTQJJ-UHFFFAOYSA-N 4-methyl-2,3-dihydroinden-1-one Chemical compound CC1=CC=CC2=C1CCC2=O RUORWXQKVXTQJJ-UHFFFAOYSA-N 0.000 description 2
LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 2
QOPRWBRNMPANKN-UHFFFAOYSA-N 5-methoxy-2,3-dihydroinden-1-one Chemical compound COC1=CC=C2C(=O)CCC2=C1 QOPRWBRNMPANKN-UHFFFAOYSA-N 0.000 description 2
CTPVGIUCSWWLNA-UHFFFAOYSA-N 8-(1,2-dihydroacenaphthylen-1-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride Chemical compound Cl.C1CN(C2C=3C=CC=C4C=CC=C(C=34)C2)CCC11C(=O)NCN1C1=CC=CC=C1 CTPVGIUCSWWLNA-UHFFFAOYSA-N 0.000 description 2
DJFQELCVNXIYMH-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride Chemical compound Cl.C1CN(C2CC3=CC=CC=C3C2)CCC11C(=O)NCN1C1=CC=CC=C1 DJFQELCVNXIYMH-UHFFFAOYSA-N 0.000 description 2
LOAMFOZCQDAROI-UHFFFAOYSA-N 8-(5,8-dichloro-1,2,3,4-tetrahydronaphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride Chemical compound Cl.C1CC=2C(Cl)=CC=C(Cl)C=2CC1N(CC1)CCC1(C(NC1)=O)N1C1=CC=CC=C1 LOAMFOZCQDAROI-UHFFFAOYSA-N 0.000 description 2
MESUCNITBHEPHP-VEIFNGETSA-N 8-[(1r)-2,3-dihydro-1h-inden-1-yl]-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride Chemical compound Cl.C1CN([C@H]2C3=CC=CC=C3CC2)CCC11C(=O)NCN1C1=CC=CC=C1 MESUCNITBHEPHP-VEIFNGETSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
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GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
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HRTUAOKEKZVEPG-UHFFFAOYSA-N n-(7-methoxy-3,4-dihydro-2h-naphthalen-1-ylidene)hydroxylamine Chemical compound C1CCC(=NO)C2=CC(OC)=CC=C21 HRTUAOKEKZVEPG-UHFFFAOYSA-N 0.000 description 1
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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
- C07D471/10—Spiro-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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
- A—HUMAN NECESSITIES
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- 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
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
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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)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Cardiology (AREA)
Hematology (AREA)
Diabetes (AREA)
Obesity (AREA)
Heart & Thoracic Surgery (AREA)
Addiction (AREA)
Hospice & Palliative Care (AREA)
Anesthesiology (AREA)
Child & Adolescent Psychology (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Lubricants (AREA)
Photoreceptors In Electrophotography (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

NO980332A 1997-01-30 1998-01-26 8-substituerte-1,3,8-triaza-spiro[4,5]dekan-4-on-derivater NO310026B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP97101409		1997-01-30
EP97119311		1997-11-05

Publications (3)

Publication Number	Publication Date
NO980332D0 NO980332D0 (no)	1998-01-26
NO980332L NO980332L (no)	1998-07-31
NO310026B1 true NO310026B1 (no)	2001-05-07

Family

ID=26145196

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO980332A NO310026B1 (no)	1997-01-30	1998-01-26	8-substituerte-1,3,8-triaza-spiro[4,5]dekan-4-on-derivater

Country Status (34)

Country	Link
US (1)	US6071925A (sh)
EP (1)	EP0856514B1 (sh)
JP (1)	JP3292457B2 (sh)
KR (1)	KR100274107B1 (sh)
CN (1)	CN1113881C (sh)
AR (1)	AR011576A1 (sh)
AT (1)	ATE202105T1 (sh)
AU (1)	AU730147B2 (sh)
BR (1)	BR9800524B1 (sh)
CA (1)	CA2226058C (sh)
CO (1)	CO4920223A1 (sh)
CZ (1)	CZ27398A3 (sh)
DE (1)	DE69800896T2 (sh)
DK (1)	DK0856514T3 (sh)
EA (1)	EA001357B1 (sh)
ES (1)	ES2158622T3 (sh)
GR (1)	GR3036523T3 (sh)
HR (1)	HRP980043B1 (sh)
HU (1)	HUP9800138A3 (sh)
ID (1)	ID19773A (sh)
IL (1)	IL123036A (sh)
MA (1)	MA26470A1 (sh)
NO (1)	NO310026B1 (sh)
NZ (1)	NZ329627A (sh)
PE (1)	PE59999A1 (sh)
PL (1)	PL324571A1 (sh)
PT (1)	PT856514E (sh)
SG (1)	SG71077A1 (sh)
SI (1)	SI0856514T1 (sh)
TR (1)	TR199800085A2 (sh)
TW (1)	TW457238B (sh)
UY (1)	UY24865A1 (sh)
YU (1)	YU2098A (sh)
ZA (1)	ZA98570B (sh)

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1997
- 1997-12-31 CA CA002226058A patent/CA2226058C/en not_active Expired - Fee Related
1998
- 1998-01-07 SG SG1998000062A patent/SG71077A1/en unknown
- 1998-01-15 YU YU2098A patent/YU2098A/sh unknown
- 1998-01-20 US US09/009,457 patent/US6071925A/en not_active Expired - Fee Related
- 1998-01-20 TR TR1998/00085A patent/TR199800085A2/xx unknown
- 1998-01-21 DK DK98100970T patent/DK0856514T3/da active
- 1998-01-21 ES ES98100970T patent/ES2158622T3/es not_active Expired - Lifetime
- 1998-01-21 AT AT98100970T patent/ATE202105T1/de active
- 1998-01-21 EP EP98100970A patent/EP0856514B1/en not_active Expired - Lifetime
- 1998-01-21 SI SI9830035T patent/SI0856514T1/xx unknown
- 1998-01-21 DE DE69800896T patent/DE69800896T2/de not_active Expired - Lifetime
- 1998-01-21 PT PT98100970T patent/PT856514E/pt unknown
- 1998-01-22 ID IDP980073A patent/ID19773A/id unknown
- 1998-01-23 CN CN98103687A patent/CN1113881C/zh not_active Expired - Fee Related
- 1998-01-23 NZ NZ329627A patent/NZ329627A/xx unknown
- 1998-01-23 IL IL12303698A patent/IL123036A/xx not_active IP Right Cessation
- 1998-01-23 ZA ZA98570A patent/ZA98570B/xx unknown
- 1998-01-26 HU HU9800138A patent/HUP9800138A3/hu unknown
- 1998-01-26 NO NO980332A patent/NO310026B1/no not_active IP Right Cessation
- 1998-01-27 HR HR980043A patent/HRP980043B1/xx not_active IP Right Cessation
- 1998-01-27 AR ARP980100349A patent/AR011576A1/es active IP Right Grant
- 1998-01-27 JP JP01371198A patent/JP3292457B2/ja not_active Expired - Fee Related
- 1998-01-27 PE PE1998000056A patent/PE59999A1/es not_active Application Discontinuation
- 1998-01-28 MA MA24950A patent/MA26470A1/fr unknown
- 1998-01-28 CO CO98003944A patent/CO4920223A1/es unknown
- 1998-01-29 PL PL98324571A patent/PL324571A1/xx unknown
- 1998-01-29 CZ CZ98273A patent/CZ27398A3/cs unknown
- 1998-01-29 AU AU52809/98A patent/AU730147B2/en not_active Ceased
- 1998-01-29 UY UY24865A patent/UY24865A1/es unknown
- 1998-01-30 BR BRPI9800524-3A patent/BR9800524B1/pt not_active IP Right Cessation
- 1998-01-30 KR KR1019980002475A patent/KR100274107B1/ko not_active Expired - Fee Related
- 1998-01-30 EA EA199800108A patent/EA001357B1/ru not_active IP Right Cessation
- 1998-02-04 TW TW087101434A patent/TW457238B/zh not_active IP Right Cessation
2001
- 2001-09-05 GR GR20010401383T patent/GR3036523T3/el unknown

Also Published As

Publication number	Publication date
SI0856514T1 (en)	2001-08-31
PT856514E (pt)	2001-10-31
AU5280998A (en)	1998-08-06
MA26470A1 (fr)	2004-12-20
UY24865A1 (es)	2000-12-29
HUP9800138A3 (en)	1999-03-01
CN1113881C (zh)	2003-07-09
KR100274107B1 (ko)	2000-12-15
JP3292457B2 (ja)	2002-06-17
JPH10212290A (ja)	1998-08-11
IL123036A0 (en)	1998-09-24
BR9800524A (pt)	2000-03-14
DE69800896T2 (de)	2002-03-28
YU2098A (sh)	2001-03-07
KR19980070900A (ko)	1998-10-26
NZ329627A (en)	1999-11-29
NO980332L (no)	1998-07-31
PL324571A1 (en)	1998-08-03
CZ27398A3 (cs)	1998-08-12
CA2226058A1 (en)	1998-07-30
PE59999A1 (es)	1999-07-01
EP0856514A1 (en)	1998-08-05
ATE202105T1 (de)	2001-06-15
AU730147B2 (en)	2001-03-01
HU9800138D0 (en)	1998-03-30
CO4920223A1 (es)	2000-05-29
DK0856514T3 (da)	2001-09-17
HUP9800138A2 (hu)	1998-09-28
TR199800085A3 (tr)	1998-08-21
TW457238B (en)	2001-10-01
EP0856514B1 (en)	2001-06-13
DE69800896D1 (de)	2001-07-19
HRP980043B1 (en)	2001-12-31
NO980332D0 (no)	1998-01-26
IL123036A (en)	2000-12-06
ID19773A (id)	1998-07-30
US6071925A (en)	2000-06-06
CA2226058C (en)	2008-01-29
TR199800085A2 (xx)	1998-08-21
SG71077A1 (en)	2000-03-21
EA001357B1 (ru)	2001-02-26
BR9800524B1 (pt)	2008-11-18
ES2158622T3 (es)	2001-09-01
EA199800108A1 (ru)	1998-10-29
HRP980043A2 (en)	1998-12-31
AR011576A1 (es)	2000-08-30
GR3036523T3 (en)	2001-12-31
ZA98570B (en)	1998-07-30
CN1191862A (zh)	1998-09-02

Publication	Publication Date	Title
NO310026B1 (no)	2001-05-07	8-substituerte-1,3,8-triaza-spiro[4,5]dekan-4-on-derivater
US6166209A (en)	2000-12-26	Piperidine derivatives
EP0921125B1 (en)	2002-01-30	1,3,8-Triazaspiro[4,5]decan-4-on derivatives
AU743983B2 (en)	2002-02-14	Diaza-spiro (3,5)nonane derivatives
NO312161B1 (no)	2002-04-02	1,3,8-Triaza-spiro(4,5)dekan-4-on-derivater, fremgangsmåter ved fremstilling derav, anvendelse derav og medikamenterinneholdende disse derivater
EP0963985B1 (en)	2003-03-12	Di-or triaza-spiro(4,5)decane derivatives
EP0963987B1 (en)	2002-08-28	Spiro(piperidine-4,1'-pyrrolo(3,4-c)pyrrole)
MXPA98000824A (en)	1999-10-14	Derivatives of 1,3,8-triaza-espiro [4.5] decan-4-ona 8-substitute

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