AP495A - Piperidine derivatives - Google Patents

Piperidine derivatives Download PDF

Info

Publication number: AP495A
Authority: AP; ARIPO
Prior art keywords: tetrazol; piperidin; methoxy; formula; phenyl
Prior art date: 1993-09-22

Application number

APAP/P/1994/000671A

Other languages

English (en)

Other versions

AP9400671A0 (en

Inventor

Duncan Robert Armour

Brian Evans

Gerald Martin Paul Giblin

Michael Menteith Hann

Tannia Hubbard

Xiao-Qing Lewel

David Middlemiss

Alan Naylor

Neil Anthony Pegg

Maria Victoria Vinader

Stephen Paul Watson

Original Assignee

Glaxo Group Ltd

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.)

1993-09-22

Filing date

1994-09-21

Publication date

1996-05-28

1993-09-22 Priority claimed from GB939319606A external-priority patent/GB9319606D0/en

1993-12-31 Priority claimed from GB9326583A external-priority patent/GB9326583D0/en

1994-09-21 Application filed by Glaxo Group Ltd filed Critical Glaxo Group Ltd

1994-10-31 Publication of AP9400671A0 publication Critical patent/AP9400671A0/xx

1996-05-28 Application granted granted Critical

1996-05-28 Publication of AP495A publication Critical patent/AP495A/en

Links

150000003053 piperidines Chemical class 0.000 title abstract description 3
150000001875 compounds Chemical class 0.000 claims description 340
150000003839 salts Chemical class 0.000 claims description 44
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 36
238000000034 method Methods 0.000 claims description 24
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
238000011282 treatment Methods 0.000 claims description 17
229910052739 hydrogen Inorganic materials 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 16
239000012453 solvate Substances 0.000 claims description 16
238000002360 preparation method Methods 0.000 claims description 15
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 12
QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 claims description 10
102100024304 Protachykinin-1 Human genes 0.000 claims description 10
101800003906 Substance P Proteins 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
102000003141 Tachykinin Human genes 0.000 claims description 9
230000009467 reduction Effects 0.000 claims description 9
108060008037 tachykinin Proteins 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000005843 halogen group Chemical group 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 5
235000019270 ammonium chloride Nutrition 0.000 claims description 5
230000001404 mediated effect Effects 0.000 claims description 5
239000008194 pharmaceutical composition Substances 0.000 claims description 5
150000002431 hydrogen Chemical group 0.000 claims description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
238000002560 therapeutic procedure Methods 0.000 claims description 3
241000124008 Mammalia Species 0.000 claims description 2
125000002252 acyl group Chemical group 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 371
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 217
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 183
239000000203 mixture Substances 0.000 description 132
239000007787 solid Substances 0.000 description 117
239000000543 intermediate Substances 0.000 description 109
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 107
239000000243 solution Substances 0.000 description 100
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 96
235000019441 ethanol Nutrition 0.000 description 77
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 65
229940093499 ethyl acetate Drugs 0.000 description 61
235000019439 ethyl acetate Nutrition 0.000 description 61
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
229910021529 ammonia Inorganic materials 0.000 description 51
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 42
239000002904 solvent Substances 0.000 description 37
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
229910052757 nitrogen Inorganic materials 0.000 description 32
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 31
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 30
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 30
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
229910052938 sodium sulfate Inorganic materials 0.000 description 28
-1 oxalic Chemical class 0.000 description 27
239000007832 Na2SO4 Substances 0.000 description 25
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 25
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
150000001412 amines Chemical class 0.000 description 20
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
238000003818 flash chromatography Methods 0.000 description 18
239000012458 free base Substances 0.000 description 18
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
206010047700 Vomiting Diseases 0.000 description 16
229960000583 acetic acid Drugs 0.000 description 16
239000012044 organic layer Substances 0.000 description 16
239000000725 suspension Substances 0.000 description 16
239000003826 tablet Substances 0.000 description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
229910000029 sodium carbonate Inorganic materials 0.000 description 15
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
239000012267 brine Substances 0.000 description 13
239000000460 chlorine Substances 0.000 description 13
239000000843 powder Substances 0.000 description 13
238000003756 stirring Methods 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
238000010992 reflux Methods 0.000 description 12
239000000284 extract Substances 0.000 description 11
238000009472 formulation Methods 0.000 description 11
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
235000011054 acetic acid Nutrition 0.000 description 10
239000010410 layer Substances 0.000 description 10
239000000047 product Substances 0.000 description 10
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 10
PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 9
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
239000002775 capsule Substances 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
230000008569 process Effects 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
LGWHVLLTRCDFDK-UHFFFAOYSA-N 2-methoxy-5-(5-methyltetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1C(C)=NN=N1 LGWHVLLTRCDFDK-UHFFFAOYSA-N 0.000 description 8
PITHNUWDJUJELK-UHFFFAOYSA-N 2-methoxy-5-(tetrazol-1-yl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC=C1N1N=NN=C1 PITHNUWDJUJELK-UHFFFAOYSA-N 0.000 description 8
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
208000002193 Pain Diseases 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 8
238000004949 mass spectrometry Methods 0.000 description 8
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 8
238000006722 reduction reaction Methods 0.000 description 8
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
239000005557 antagonist Substances 0.000 description 7
229910052801 chlorine Inorganic materials 0.000 description 7
238000001816 cooling Methods 0.000 description 7
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238000010511 deprotection reaction Methods 0.000 description 7
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235000019341 magnesium sulphate Nutrition 0.000 description 7
238000004452 microanalysis Methods 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
239000012321 sodium triacetoxyborohydride Substances 0.000 description 7
UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 6
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
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GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
238000004440 column chromatography Methods 0.000 description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 6
239000011737 fluorine Substances 0.000 description 6
229910052731 fluorine Inorganic materials 0.000 description 6
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
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UBSPKGKFFQKZJB-UHFFFAOYSA-N methyl 4-nitrobutanoate Chemical compound COC(=O)CCC[N+]([O-])=O UBSPKGKFFQKZJB-UHFFFAOYSA-N 0.000 description 6
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230000005855 radiation Effects 0.000 description 6
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LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
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HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
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GFMAFYNUQDLPBP-UHFFFAOYSA-N 2-phenylpiperidin-3-amine Chemical compound NC1CCCNC1C1=CC=CC=C1 GFMAFYNUQDLPBP-UHFFFAOYSA-N 0.000 description 3
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NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
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JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
- 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
- A61P25/04—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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (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)
Public Health (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Hospice & Palliative Care (AREA)
Otolaryngology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)

APAP/P/1994/000671A 1993-09-22 1994-09-21 Piperidine derivatives AP495A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB939319606A GB9319606D0 (en)	1993-09-22	1993-09-22	Chemical compounds
GB9326583A GB9326583D0 (en)	1993-12-31	1993-12-31	Chemical compounds

Publications (2)

Publication Number	Publication Date
AP9400671A0 AP9400671A0 (en)	1994-10-31
AP495A true AP495A (en)	1996-05-28

Family

ID=26303560

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1994/000671A AP495A (en)	1993-09-22	1994-09-21	Piperidine derivatives

Country Status (29)

Country	Link
US (2)	US5703240A (is)
EP (1)	EP0720609B1 (is)
JP (2)	JP2865872B2 (is)
CN (1)	CN1061041C (is)
AP (1)	AP495A (is)
AT (1)	ATE173255T1 (is)
AU (1)	AU681190B2 (is)
BG (1)	BG62169B1 (is)
CA (1)	CA2172529A1 (is)
CO (1)	CO4290298A1 (is)
CZ (1)	CZ285479B6 (is)
DE (1)	DE69414590T2 (is)
DK (1)	DK0720609T3 (is)
ES (1)	ES2123829T3 (is)
FI (1)	FI961270A7 (is)
GR (1)	GR3029354T3 (is)
HR (1)	HRP940575B1 (is)
HU (1)	HU217428B (is)
IL (1)	IL111002A (is)
IS (1)	IS4208A (is)
NO (1)	NO307830B1 (is)
NZ (1)	NZ273614A (is)
OA (1)	OA10576A (is)
PE (1)	PE18295A1 (is)
PL (1)	PL179585B1 (is)
SI (1)	SI0720609T1 (is)
SK (1)	SK280901B6 (is)
UA (1)	UA44711C2 (is)
WO (1)	WO1995008549A1 (is)

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- 1994-09-19 IL IL11100294A patent/IL111002A/en not_active IP Right Cessation
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- 1994-09-20 SI SI9430208T patent/SI0720609T1/xx unknown
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Also Published As

Publication number	Publication date
ES2123829T3 (es)	1999-01-16
CN1061041C (zh)	2001-01-24
AU681190B2 (en)	1997-08-21
BG62169B1 (bg)	1999-04-30
JPH11106341A (ja)	1999-04-20
NO961156D0 (no)	1996-03-21
OA10576A (en)	2002-06-03
JP2865872B2 (ja)	1999-03-08
IL111002A0 (en)	1994-11-28
EP0720609A1 (en)	1996-07-10
NO961156L (no)	1996-05-21
NZ273614A (en)	1997-09-22
SK280901B6 (sk)	2000-09-12
EP0720609B1 (en)	1998-11-11
HRP940575B1 (en)	2000-06-30
PL179585B1 (pl)	2000-09-29
HUT75648A (en)	1997-05-28
DE69414590D1 (de)	1998-12-17
AU7697494A (en)	1995-04-10
US5703240A (en)	1997-12-30
CN1135218A (zh)	1996-11-06
GR3029354T3 (en)	1999-05-28
UA44711C2 (uk)	2002-03-15
IL111002A (en)	1998-09-24
WO1995008549A1 (en)	1995-03-30
HK1004219A1 (en)	1998-11-20
DE69414590T2 (de)	1999-04-15
PE18295A1 (es)	1995-07-27
CO4290298A1 (es)	1996-04-17
HRP940575A2 (en)	1997-02-28
JPH09505275A (ja)	1997-05-27
HU9600722D0 (en)	1996-05-28
IS4208A (is)	1995-03-23
FI961270A7 (fi)	1996-05-03
DK0720609T3 (da)	1999-07-26
CA2172529A1 (en)	1995-03-30
SK38396A3 (en)	1997-02-05
BG100487A (bg)	1996-12-31
FI961270A0 (fi)	1996-03-19
US5843966A (en)	1998-12-01
CZ83096A3 (en)	1996-09-11
PL313619A1 (en)	1996-07-08
NO307830B1 (no)	2000-06-05
HU217428B (hu)	2000-01-28
CZ285479B6 (cs)	1999-08-11
AP9400671A0 (en)	1994-10-31
SI0720609T1 (en)	1999-02-28
ATE173255T1 (de)	1998-11-15

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