HRP980613A2 - 1,3,8-triaza-spiro/4,5/decan-4-on derivatives - Google Patents

1,3,8-triaza-spiro/4,5/decan-4-on derivatives

Info

Publication number: HRP980613A2
Authority: HR; Croatia
Prior art keywords: phenyl; spiro; triaza; decan; lower alkyl
Prior art date: 1997-12-05

Application number

HR97121427.5A

Other languages

English (en)

Croatian (hr)

Inventor

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.)

1997-12-05

Filing date

1998-12-04

Publication date

1999-08-31

1998-12-04 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1999-08-31 Publication of HRP980613A2 publication Critical patent/HRP980613A2/hr

Links

150000001875 compounds Chemical class 0.000 claims description 185
239000000203 mixture Substances 0.000 claims description 84
239000001257 hydrogen Substances 0.000 claims description 34
229910052739 hydrogen Inorganic materials 0.000 claims description 34
-1 cyanomethyl Chemical group 0.000 claims description 29
125000000217 alkyl group Chemical group 0.000 claims description 27
238000000034 method Methods 0.000 claims description 20
150000003839 salts Chemical class 0.000 claims description 17
150000002431 hydrogen Chemical group 0.000 claims description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
108090000622 Nociceptin Proteins 0.000 claims description 13
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 13
238000006243 chemical reaction Methods 0.000 claims description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
208000002193 Pain Diseases 0.000 claims description 8
239000002253 acid Substances 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
125000005037 alkyl phenyl group Chemical group 0.000 claims description 6
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
239000000546 pharmaceutical excipient Substances 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
GHRFRJDKSJJJFQ-UHFFFAOYSA-N 8-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CN(C2CC3CCCCC3CC2)CCC11C(=O)NCN1C1=CC=CC=C1 GHRFRJDKSJJJFQ-UHFFFAOYSA-N 0.000 claims description 5
WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
208000035475 disorder Diseases 0.000 claims description 5
229940079593 drug Drugs 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
229910052740 iodine Inorganic materials 0.000 claims description 5
238000006268 reductive amination reaction Methods 0.000 claims description 5
208000024827 Alzheimer disease Diseases 0.000 claims description 4
208000000044 Amnesia Diseases 0.000 claims description 4
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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
230000036506 anxiety Effects 0.000 claims description 4
230000036461 convulsion Effects 0.000 claims description 4
125000004122 cyclic group Chemical group 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
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230000000926 neurological effect Effects 0.000 claims description 4
235000020824 obesity Nutrition 0.000 claims description 4
238000007363 ring formation reaction Methods 0.000 claims description 4
230000008733 trauma Effects 0.000 claims description 4
125000004135 2-norbornyl group Chemical group [H]C1([H])C([H])([H])C2([H])C([H])([H])C1([H])C([H])([H])C2([H])* 0.000 claims description 3
DZVZUWSJJIGMRV-UHFFFAOYSA-N 8-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-2-yl)-3-methyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CN(C2CC3CCCCC3CC2)CCC21C(=O)N(C)CN2C1=CC=CC=C1 DZVZUWSJJIGMRV-UHFFFAOYSA-N 0.000 claims description 3
230000004872 arterial blood pressure Effects 0.000 claims description 3
125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 claims description 3
238000006722 reduction reaction Methods 0.000 claims description 3
GWNDTWSMNIBSRN-UHFFFAOYSA-N 8-cyclodecyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CN(C2CCCCCCCCC2)CCC11C(=O)NCN1C1=CC=CC=C1 GWNDTWSMNIBSRN-UHFFFAOYSA-N 0.000 claims description 2
IAUDPLBTMXJMKC-UHFFFAOYSA-N 8-cyclononyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound C1CN(C2CCCCCCCC2)CCC11C(=O)NCN1C1=CC=CC=C1 IAUDPLBTMXJMKC-UHFFFAOYSA-N 0.000 claims description 2
230000029936 alkylation Effects 0.000 claims description 2
238000005804 alkylation reaction Methods 0.000 claims description 2
125000002648 azanetriyl group Chemical group *N(*)* 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
238000005574 benzylation reaction Methods 0.000 claims description 2
239000004305 biphenyl Substances 0.000 claims description 2
BNRNAKTVFSZAFA-UHFFFAOYSA-N hydrindane Chemical group C1CCCC2CCCC21 BNRNAKTVFSZAFA-UHFFFAOYSA-N 0.000 claims description 2
150000002825 nitriles Chemical class 0.000 claims description 2
125000004306 triazinyl group Chemical group 0.000 claims description 2
102000048266 Nociceptin Human genes 0.000 claims 4
201000010099 disease Diseases 0.000 claims 3
206010013663 drug dependence Diseases 0.000 claims 2
208000011117 substance-related disease Diseases 0.000 claims 2
125000005508 decahydronaphthalenyl group Chemical group 0.000 claims 1
DIOQZVSQGTUSAI-UHFFFAOYSA-N n-butylhexane Natural products CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 claims 1
238000007429 general method Methods 0.000 description 82
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
239000007787 solid Substances 0.000 description 52
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 47
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
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 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
QFXKFJHPXRIMOV-UHFFFAOYSA-N 8-cyclodecyl-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride Chemical compound Cl.C1CN(C2CCCCCCCCC2)CCC11C(=O)NCN1C1=CC=CC=C1 QFXKFJHPXRIMOV-UHFFFAOYSA-N 0.000 description 25
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
238000002844 melting Methods 0.000 description 22
230000008018 melting Effects 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 21
229910052938 sodium sulfate Inorganic materials 0.000 description 21
235000011152 sodium sulphate Nutrition 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
239000000843 powder Substances 0.000 description 17
239000000243 solution Substances 0.000 description 16
239000012044 organic layer Substances 0.000 description 15
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
SXOZDDAFVJANJP-UHFFFAOYSA-N cyclodecanone Chemical compound O=C1CCCCCCCCC1 SXOZDDAFVJANJP-UHFFFAOYSA-N 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
239000012074 organic phase Substances 0.000 description 11
238000002953 preparative HPLC Methods 0.000 description 11
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
235000011114 ammonium hydroxide Nutrition 0.000 description 10
239000000741 silica gel Substances 0.000 description 10
229910002027 silica gel Inorganic materials 0.000 description 10
102400001111 Nociceptin Human genes 0.000 description 9
239000000908 ammonium hydroxide Substances 0.000 description 9
239000013078 crystal Substances 0.000 description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
150000003840 hydrochlorides Chemical class 0.000 description 8
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 7
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
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RIBPTKSALUVUKH-UHFFFAOYSA-N 8-(1,2,3,4,4a,5,6,7,8,8a-decahydronaphthalen-2-yl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride Chemical compound Cl.C1CN(C2CC3CCCCC3CC2)CCC11C(=O)NCN1C1=CC=CC=C1 RIBPTKSALUVUKH-UHFFFAOYSA-N 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
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QUXHCILOWRXCEO-UHFFFAOYSA-M magnesium;butane;chloride Chemical compound [Mg+2].[Cl-].CCC[CH2-] QUXHCILOWRXCEO-UHFFFAOYSA-M 0.000 description 5
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BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
239000007858 starting material Substances 0.000 description 5
SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 4
VGVHNLRUAMRIEW-UHFFFAOYSA-N 4-methylcyclohexan-1-one Chemical compound CC1CCC(=O)CC1 VGVHNLRUAMRIEW-UHFFFAOYSA-N 0.000 description 4
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GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 4
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230000027455 binding Effects 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
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WKGFCULYSBLJSJ-UHFFFAOYSA-N methyl 2-(8-cyclodecyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetate Chemical compound C1CN(C2CCCCCCCCC2)CCC21C(=O)N(CC(=O)OC)CN2C1=CC=CC=C1 WKGFCULYSBLJSJ-UHFFFAOYSA-N 0.000 description 3
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229920006395 saturated elastomer Polymers 0.000 description 3
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229910000104 sodium hydride Inorganic materials 0.000 description 3
239000002904 solvent Substances 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
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YEVWUNLCHKVBKM-UHFFFAOYSA-N 1-phenyl-8-(3-phenylcyclohexyl)-1,3,8-triazaspiro[4.5]decan-4-one;hydrochloride Chemical compound Cl.C1CN(C2CC(CCC2)C=2C=CC=CC=2)CCC11C(=O)NCN1C1=CC=CC=C1 YEVWUNLCHKVBKM-UHFFFAOYSA-N 0.000 description 2
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DCSKAMGZSIRJAQ-UHFFFAOYSA-N 4-(2-methylbutan-2-yl)cyclohexan-1-one Chemical compound CCC(C)(C)C1CCC(=O)CC1 DCSKAMGZSIRJAQ-UHFFFAOYSA-N 0.000 description 2
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IUAPXXJPOOMKMF-UHFFFAOYSA-N 8-benzyl-1-(3-methylphenyl)-1,3,8-triazaspiro[4.5]dec-2-en-4-one Chemical compound CC1=CC=CC(N2C3(CCN(CC=4C=CC=CC=4)CC3)C(=O)N=C2)=C1 IUAPXXJPOOMKMF-UHFFFAOYSA-N 0.000 description 2
JAEHRJNISMZWCV-UHFFFAOYSA-N 8-benzyl-1-(4-chlorophenyl)-1,3,8-triazaspiro[4.5]dec-2-en-4-one Chemical compound C1=CC(Cl)=CC=C1N1C2(CCN(CC=3C=CC=CC=3)CC2)C(=O)N=C1 JAEHRJNISMZWCV-UHFFFAOYSA-N 0.000 description 2
MPVIWMLYFVQZED-UHFFFAOYSA-N 8-benzyl-1-(4-methylphenyl)-1,3,8-triazaspiro[4.5]dec-2-en-4-one Chemical compound C1=CC(C)=CC=C1N1C2(CCN(CC=3C=CC=CC=3)CC2)C(=O)N=C1 MPVIWMLYFVQZED-UHFFFAOYSA-N 0.000 description 2
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239000003638 chemical reducing agent Substances 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
CGZZMOTZOONQIA-UHFFFAOYSA-N cycloheptanone Chemical compound O=C1CCCCCC1 CGZZMOTZOONQIA-UHFFFAOYSA-N 0.000 description 1
IIRFCWANHMSDCG-UHFFFAOYSA-N cyclooctanone Chemical compound O=C1CCCCCCC1 IIRFCWANHMSDCG-UHFFFAOYSA-N 0.000 description 1
UPOSSYJVWXLPTA-UHFFFAOYSA-N cycloundecanone Chemical compound O=C1CCCCCCCCCC1 UPOSSYJVWXLPTA-UHFFFAOYSA-N 0.000 description 1
125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
230000006735 deficit Effects 0.000 description 1
YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
230000006806 disease prevention Effects 0.000 description 1
208000037765 diseases and disorders Diseases 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
JMNJYGMAUMANNW-FIXZTSJVSA-N dynorphin a Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 JMNJYGMAUMANNW-FIXZTSJVSA-N 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
239000006274 endogenous ligand Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
OZIDXCYIYGSQRU-UHFFFAOYSA-N ethyl 5-(8-cyclodecyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)pentanoate;hydrochloride Chemical compound Cl.C1CN(C2CCCCCCCCC2)CCC21C(=O)N(CCCCC(=O)OCC)CN2C1=CC=CC=C1 OZIDXCYIYGSQRU-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
239000013604 expression vector Substances 0.000 description 1
239000003925 fat Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000011888 foil Substances 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
239000008011 inorganic excipient Substances 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
229960004903 invert sugar Drugs 0.000 description 1
150000004694 iodide salts Chemical class 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000003446 ligand Substances 0.000 description 1
230000003137 locomotive effect Effects 0.000 description 1
230000006742 locomotor activity Effects 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
ZFRIZGKGVHDLOM-UHFFFAOYSA-N methyl 2-(8-cyclodecyl-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)acetate;hydrochloride Chemical compound Cl.C1CN(C2CCCCCCCCC2)CCC21C(=O)N(CC(=O)OC)CN2C1=CC=CC=C1 ZFRIZGKGVHDLOM-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
230000003040 nociceptive effect Effects 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000008012 organic excipient Substances 0.000 description 1
150000002905 orthoesters Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
239000008188 pellet Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002400 pro-nociceptive effect Effects 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000002731 protein assay Methods 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
239000000018 receptor agonist Substances 0.000 description 1
229940044601 receptor agonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
235000013599 spices Nutrition 0.000 description 1
FEYUTRZPSFLEST-UHFFFAOYSA-N spiro[5.5]undecan-4-one Chemical compound C1C(=O)CCCC11CCCCC1 FEYUTRZPSFLEST-UHFFFAOYSA-N 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000010959 steel Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
HTSABYAWKQAHBT-UHFFFAOYSA-N trans 3-methylcyclohexanol Natural products CC1CCCC(O)C1 HTSABYAWKQAHBT-UHFFFAOYSA-N 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A61P25/20—Hypnotics; Sedatives
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- 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
- A61P25/24—Antidepressants
- 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
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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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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
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Hematology (AREA)
Diabetes (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Hospice & Palliative Care (AREA)
Addiction (AREA)
Child & Adolescent Psychology (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Non-Silver Salt Photosensitive Materials And Non-Silver Salt Photography (AREA)
Color Printing (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

HR97121427.5A 1997-12-05 1998-12-04 1,3,8-triaza-spiro/4,5/decan-4-on derivatives HRP980613A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP97121427		1997-12-05

Publications (1)

Publication Number	Publication Date
HRP980613A2 true HRP980613A2 (en)	1999-08-31

Family

ID=8227753

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HR97121427.5A HRP980613A2 (en)	1997-12-05	1998-12-04	1,3,8-triaza-spiro/4,5/decan-4-on derivatives

Country Status (29)

Country	Link
US (1)	US6043366A (fr)
JP (1)	JP3366868B2 (fr)
KR (1)	KR19990062800A (fr)
CN (1)	CN1118467C (fr)
AR (1)	AR016428A1 (fr)
AT (1)	ATE212635T1 (fr)
AU (1)	AU744338B2 (fr)
BR (1)	BR9805297B1 (fr)
CA (1)	CA2255171C (fr)
CO (1)	CO4990965A1 (fr)
CZ (1)	CZ399698A3 (fr)
DE (1)	DE69803653T2 (fr)
DK (1)	DK0921125T3 (fr)
ES (1)	ES2170446T3 (fr)
HR (1)	HRP980613A2 (fr)
HU (1)	HUP9802807A3 (fr)
ID (1)	ID21413A (fr)
IL (1)	IL127399A0 (fr)
MA (1)	MA26573A1 (fr)
NO (1)	NO312161B1 (fr)
NZ (1)	NZ333159A (fr)
PE (1)	PE135299A1 (fr)
PL (1)	PL330062A1 (fr)
PT (1)	PT921125E (fr)
SG (1)	SG71173A1 (fr)
TR (1)	TR199802520A2 (fr)
TW (1)	TW408123B (fr)
YU (1)	YU55198A (fr)
ZA (1)	ZA9811128B (fr)

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US6686370B2 (en) *	1999-12-06	2004-02-03	Euro-Celtique S.A.	Triazospiro compounds having nociceptin receptor affinity
EP1420020B1 (fr) *	2001-07-23	2008-05-28	Banyu Pharmaceutical Co., Ltd.	Derive de 4-oxoimidazolidine-2-spiropiperidine
PT1491212E (pt)	2002-03-29	2012-11-16	Mitsubishi Tanabe Pharma Corp	Medicamento para distúrbios de sono
AU2003268512A1 (en) *	2002-09-09	2004-03-29	Janssen Pharmaceutica N.V.	Hydroxy alkyl substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives useful for the treatment of ORL-1 receptor mediated disorders
WO2004058727A1 (fr) *	2002-12-20	2004-07-15	Bayer Pharmaceuticals Corporation	3,5-dihydro-4-h-imidazol-4-ones substitues utilises dans le traitement de l'obesite
AU2004241134A1 (en) *	2003-05-23	2004-12-02	Zealand Pharma A/S	Triaza-spiro compounds as nociceptin analogues and uses thereof
ES2297502T3 (es) *	2003-10-23	2008-05-01	F. Hoffmann-La Roche Ag	Derivados de triaza-espiropiperidinas para uso como inhibidores de glyt-1 en el tratamiento de trastornos neurologicos y neuropsiquiatricos.
US20060178390A1 (en) *	2004-08-02	2006-08-10	Alfonzo Jordan	1,3,8-Triazaspiro[4,5]decan-4-one derivatives useful for the treatment of ORL-1 receptor mediated disorders
KR20070113305A (ko) *	2005-03-22	2007-11-28	에프. 호프만-라 로슈 아게	Ｄｐｐ-ｉｖ 저해제의 신규 염 및 동질이상체
EP2035420A2 (fr) *	2006-06-20	2009-03-18	Wyeth a Corporation of the State of Delaware	Inhibiteurs du canal potassique kv1.5
CN101622254B (zh) *	2006-11-28	2013-05-29	詹森药业有限公司	3-(3-氨基-2-(r)-羟基-丙基)-1-(4-氟-苯基)-8-(8-甲基-萘-1-基甲基)-1,3,8-三氮杂-螺[4.5]癸烷-4-酮的盐
MX2009009355A (es) *	2007-03-01	2009-09-11	Mitsubishi Tanabe Pharma Corp	Compuesto de bencimidazol y uso farmaceutico del mismo.
MX2009011006A (es) *	2007-04-09	2009-11-02	Janssen Pharmaceutica Nv	Derivados de 1,3,8-trisustituido-1,3,8-triaza-espiro[4.5]decano-4- ona como ligandos del receptor de orl-1 para el tratamiento de ansiedad y depresion.
PA8801401A1 (es) *	2007-10-25	2009-05-15	Janssen Pharmaceutica Nv	Arilindenopirimidinas y su uso como adenosina a2a
TW201016675A (en) *	2008-09-16	2010-05-01	Mitsubishi Tanabe Pharma Corp	Crystalline benzoimidazole compound and salt thereof
US20100076003A1 (en) *	2008-09-19	2010-03-25	Kathleen Battista	5-oxazolidin-2-one substituted 1,3,8-triazaspiro[4.5]decan-4-one derivatives useful as orl-1 receptor modulators
WO2010037081A1 (fr) *	2008-09-29	2010-04-01	Palatin Technologies, Inc.	Composés de spiropipéridine spécifiques du récepteur de la mélanocortine
CA2765415A1 (fr)	2009-06-16	2010-12-23	Merck Sharp & Dohme Corp.	1,3,8-triazaspiro[4,5]decane-2,4-diones substituees
CN107849044B (zh) *	2015-07-03	2021-06-25	豪夫迈·罗氏有限公司	作为ddr1抑制剂的三氮杂-螺癸酮类化合物
WO2023198181A1 (fr) *	2022-04-15	2023-10-19	The Chinese University Of Hong Kong	Nucléosides carbobicycliques pour le traitement d'une infection virale

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MA19091A1 (fr) *	1980-03-10	1981-10-01	Janssen Pharmaceutica Nv	Nouveaux derives de i-(4-aryl-cyclohexyl)piperidine .
US4329353A (en) *	1980-10-22	1982-05-11	Janssen Pharmaceutica, N.V.	1-(4-Aryl-cyclohexyl)piperidine derivatives, method of use thereof and pharmaceutical compositions thereof
GR73633B (fr) *	1980-03-10	1984-03-26	Janssen Pharmaceutica Nv
ATE67769T1 (de) *	1983-01-25	1991-10-15	Ciba Geigy Ag	Neue peptidderivate.
JPS6012357B2 (ja) *	1984-01-23	1985-04-01	吉富製薬株式会社	脂環式誘導体
CA2226058C (fr) *	1997-01-30	2008-01-29	F. Hoffmann-La Roche Ag	Derives de substitution en 8 de 1,3,8-triazaspiro[4.5]decan-4-one

1998
- 1998-11-27 PT PT98122511T patent/PT921125E/pt unknown
- 1998-11-27 AT AT98122511T patent/ATE212635T1/de active
- 1998-11-27 ES ES98122511T patent/ES2170446T3/es not_active Expired - Lifetime
- 1998-11-27 DK DK98122511T patent/DK0921125T3/da active
- 1998-11-27 DE DE69803653T patent/DE69803653T2/de not_active Expired - Lifetime
- 1998-12-03 US US09/204,184 patent/US6043366A/en not_active Expired - Fee Related
- 1998-12-03 AR ARP980106141A patent/AR016428A1/es active IP Right Grant
- 1998-12-03 ID IDP981576A patent/ID21413A/id unknown
- 1998-12-03 PE PE1998001176A patent/PE135299A1/es not_active Application Discontinuation
- 1998-12-03 PL PL98330062A patent/PL330062A1/xx unknown
- 1998-12-03 YU YU55198A patent/YU55198A/sh unknown
- 1998-12-03 SG SG1998005141A patent/SG71173A1/en unknown
- 1998-12-03 CA CA002255171A patent/CA2255171C/fr not_active Expired - Fee Related
- 1998-12-03 NZ NZ333159A patent/NZ333159A/en unknown
- 1998-12-04 CZ CZ983996A patent/CZ399698A3/cs unknown
- 1998-12-04 KR KR1019980053080A patent/KR19990062800A/ko not_active Ceased
- 1998-12-04 JP JP34527898A patent/JP3366868B2/ja not_active Expired - Fee Related
- 1998-12-04 CN CN98122759A patent/CN1118467C/zh not_active Expired - Fee Related
- 1998-12-04 HU HU9802807A patent/HUP9802807A3/hu unknown
- 1998-12-04 TW TW087120132A patent/TW408123B/zh not_active IP Right Cessation
- 1998-12-04 NO NO19985684A patent/NO312161B1/no not_active IP Right Cessation
- 1998-12-04 CO CO98072457A patent/CO4990965A1/es unknown
- 1998-12-04 ZA ZA9811128A patent/ZA9811128B/xx unknown
- 1998-12-04 IL IL12739998A patent/IL127399A0/xx unknown
- 1998-12-04 HR HR97121427.5A patent/HRP980613A2/hr not_active Application Discontinuation
- 1998-12-04 BR BRPI9805297-7A patent/BR9805297B1/pt not_active IP Right Cessation
- 1998-12-04 AU AU96087/98A patent/AU744338B2/en not_active Ceased
- 1998-12-04 TR TR1998/02520A patent/TR199802520A2/xx unknown
- 1998-12-04 MA MA25369A patent/MA26573A1/fr unknown

Also Published As

Publication number	Publication date
NZ333159A (en)	2000-06-23
CZ399698A3 (cs)	1999-06-16
BR9805297A (pt)	2000-02-01
CA2255171C (fr)	2009-09-29
PE135299A1 (es)	2000-01-18
PT921125E (pt)	2002-06-28
AR016428A1 (es)	2001-07-04
PL330062A1 (en)	1999-06-07
NO312161B1 (no)	2002-04-02
HUP9802807A2 (hu)	1999-08-30
SG71173A1 (en)	2000-03-21
NO985684D0 (no)	1998-12-04
DK0921125T3 (da)	2002-05-13
AU744338B2 (en)	2002-02-21
JPH11228575A (ja)	1999-08-24
ZA9811128B (en)	1999-06-07
KR19990062800A (ko)	1999-07-26
AU9608798A (en)	1999-06-24
JP3366868B2 (ja)	2003-01-14
TW408123B (en)	2000-10-11
DE69803653D1 (de)	2002-03-14
TR199802520A3 (tr)	1999-06-21
CN1118467C (zh)	2003-08-20
CO4990965A1 (es)	2000-12-26
CA2255171A1 (fr)	1999-06-05
US6043366A (en)	2000-03-28
ID21413A (id)	1999-06-10
HU9802807D0 (en)	1999-02-01
BR9805297B1 (pt)	2010-07-13
CN1222521A (zh)	1999-07-14
IL127399A0 (en)	1999-10-28
YU55198A (sh)	2001-12-26
ES2170446T3 (es)	2002-08-01
ATE212635T1 (de)	2002-02-15
DE69803653T2 (de)	2002-08-29
HUP9802807A3 (en)	2000-01-28
NO985684L (no)	1999-06-07
MA26573A1 (fr)	2004-12-20
TR199802520A2 (xx)	1999-06-21

Legal Events

Date	Code	Title
1999-08-31	A1OB	Publication of a patent application
2000-02-24	AIPI	Request for the grant of a patent on the basis of a substantive examination of a patent application
2007-01-22	ODBI	Application refused

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