JP2001507021A - 鎮痛作用を有する新規な化合物 - Google Patents
鎮痛作用を有する新規な化合物Info
- Publication number
- JP2001507021A JP2001507021A JP52867098A JP52867098A JP2001507021A JP 2001507021 A JP2001507021 A JP 2001507021A JP 52867098 A JP52867098 A JP 52867098A JP 52867098 A JP52867098 A JP 52867098A JP 2001507021 A JP2001507021 A JP 2001507021A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- independently
- optionally
- 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.)
- Ceased
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 75
- 230000000202 analgesic effect Effects 0.000 title description 5
- 208000002193 Pain Diseases 0.000 claims abstract description 12
- 230000036407 pain Effects 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- -1 tetrahydroquinyl Chemical group 0.000 claims description 40
- 238000004519 manufacturing process Methods 0.000 claims description 20
- 238000002360 preparation method Methods 0.000 claims description 17
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 125000004429 atom Chemical group 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 6
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 208000020431 spinal cord injury Diseases 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 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
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 239000000651 prodrug Substances 0.000 claims description 4
- 229940002612 prodrug Drugs 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 108010029485 Protein Isoforms Proteins 0.000 claims description 3
- 102000001708 Protein Isoforms Human genes 0.000 claims description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical class [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- 150000003840 hydrochlorides Chemical class 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 238000006268 reductive amination reaction Methods 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical class OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 claims description 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 2
- 150000004982 aromatic amines Chemical class 0.000 claims description 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 230000008859 change Effects 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 2
- 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 2
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001725 pyrenyl group Chemical group 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 5
- 208000010643 digestive system disease Diseases 0.000 claims 2
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 2
- 239000000032 diagnostic agent Substances 0.000 claims 1
- 229940039227 diagnostic agent Drugs 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000000144 pharmacologic effect Effects 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- 208000016702 sympathetic nervous system disease Diseases 0.000 claims 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 6
- 239000000203 mixture Substances 0.000 description 71
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 235000019439 ethyl acetate Nutrition 0.000 description 21
- 238000004458 analytical method Methods 0.000 description 19
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- 239000003921 oil Substances 0.000 description 14
- 239000012074 organic phase Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 12
- 239000000538 analytical sample Substances 0.000 description 11
- 239000012267 brine Substances 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 238000004587 chromatography analysis Methods 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- DVSLBDBGAXXLKZ-UHFFFAOYSA-N 2,3-diethylbenzamide Chemical compound CCC1=CC=CC(C(N)=O)=C1CC DVSLBDBGAXXLKZ-UHFFFAOYSA-N 0.000 description 7
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 239000012458 free base Substances 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 239000002287 radioligand Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 210000002683 foot Anatomy 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000010936 titanium Substances 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- JLNGEXDJAQASHD-UHFFFAOYSA-N N,N-Diethylbenzamide Chemical compound CCN(CC)C(=O)C1=CC=CC=C1 JLNGEXDJAQASHD-UHFFFAOYSA-N 0.000 description 5
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 5
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 108700023159 delta Opioid Receptors Proteins 0.000 description 5
- 102000048124 delta Opioid Receptors Human genes 0.000 description 5
- 210000004209 hair Anatomy 0.000 description 5
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 5
- 239000008188 pellet Substances 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
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- 229910052763 palladium Inorganic materials 0.000 description 4
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
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- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 3
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 3
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0446—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/041—Heterocyclic compounds
- A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
- A61K51/0455—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- 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
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- 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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- 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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/14—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/56—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9604786A SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | New compounds |
| SE9604786-5 | 1996-12-20 | ||
| PCT/SE1997/002051 WO1998028270A1 (en) | 1996-12-20 | 1997-12-09 | Novel compounds with analgesic effect |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001507021A true JP2001507021A (ja) | 2001-05-29 |
| JP2001507021A5 JP2001507021A5 (enExample) | 2005-08-11 |
Family
ID=20405139
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP52867098A Ceased JP2001507021A (ja) | 1996-12-20 | 1997-12-09 | 鎮痛作用を有する新規な化合物 |
Country Status (31)
| Country | Link |
|---|---|
| US (3) | US6153626A (enExample) |
| EP (2) | EP1428821A1 (enExample) |
| JP (1) | JP2001507021A (enExample) |
| KR (1) | KR20000069600A (enExample) |
| CN (2) | CN1539824A (enExample) |
| AR (1) | AR010378A1 (enExample) |
| AT (1) | ATE266638T1 (enExample) |
| AU (1) | AU738002B2 (enExample) |
| BR (1) | BR9713785A (enExample) |
| CA (1) | CA2274117A1 (enExample) |
| CZ (1) | CZ220099A3 (enExample) |
| DE (1) | DE69729115T2 (enExample) |
| DK (1) | DK0946510T3 (enExample) |
| EE (1) | EE03966B1 (enExample) |
| ES (1) | ES2219783T3 (enExample) |
| HU (1) | HUP0000613A3 (enExample) |
| ID (1) | ID21662A (enExample) |
| IL (1) | IL130536A0 (enExample) |
| IS (1) | IS5078A (enExample) |
| MY (1) | MY132705A (enExample) |
| NO (1) | NO313632B1 (enExample) |
| NZ (1) | NZ336028A (enExample) |
| PL (1) | PL188945B1 (enExample) |
| PT (1) | PT946510E (enExample) |
| RU (1) | RU2193030C2 (enExample) |
| SE (1) | SE9604786D0 (enExample) |
| SK (1) | SK283300B6 (enExample) |
| TR (1) | TR199901411T2 (enExample) |
| UA (1) | UA54481C2 (enExample) |
| WO (1) | WO1998028270A1 (enExample) |
| ZA (1) | ZA9711049B (enExample) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2005525381A (ja) * | 2002-03-13 | 2005-08-25 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ヒストンデアセチラーゼの新規な阻害剤としてのアミノ誘導体 |
| JP2008137997A (ja) * | 2006-11-10 | 2008-06-19 | Otsuka Pharmaceut Co Ltd | 医薬 |
| JP2010095543A (ja) * | 1998-03-10 | 2010-04-30 | Research Triangle Inst | 新規なオピエート化合物、その調製法及び使用法 |
| JP4754068B2 (ja) * | 1997-12-24 | 2011-08-24 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | δ−オピオイドレセプターに結合する4−[アリール(ピペリジン−4−イル)]アミノベンズアミド類 |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9504661D0 (sv) | 1995-12-22 | 1995-12-22 | Astra Pharma Inc | New compounds |
| TW548271B (en) * | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| US6974825B1 (en) | 1996-12-20 | 2005-12-13 | Astrazeneca Canada Inc. | Compounds with analgesic effect |
| SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | Astra Pharma Inc | New compounds |
| AU2003220725B2 (en) * | 1997-12-24 | 2006-06-01 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor |
| US6900228B1 (en) | 1998-03-10 | 2005-05-31 | Research Triangle Institute | Opiate compounds, methods of making and methods of use |
| US6436959B1 (en) | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
| SE9904674D0 (sv) * | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| SE9904673D0 (sv) | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| SE9904675D0 (sv) * | 1999-12-20 | 1999-12-20 | Astra Pharma Inc | Novel compounds |
| AU2063601A (en) | 1999-12-22 | 2001-07-03 | Ortho-Mcneil Pharmaceutical, Inc. | 4-(aryl(8-azabicyclo(3.2.1)octan-3-yl))aminobenzoic acid derivatives |
| AU3231901A (en) | 2000-02-18 | 2001-08-27 | Meiji Seika Kaisha | Phenoxyalkylamine derivatives useful as opioid delta receptor agonists |
| CN1426411A (zh) | 2000-03-03 | 2003-06-25 | 奥索-麦克尼尔药品公司 | 3-(二芳基亚甲基)-8-氮杂双环[3.2.1]辛烷衍生物 |
| US6790854B2 (en) | 2000-03-24 | 2004-09-14 | Meiji Seika Kaisha, Ltd. | Diphenylalkylamine derivatives useful as opioid receptor agonists |
| SE0001209D0 (sv) | 2000-04-04 | 2000-04-04 | Astrazeneca Canada Inc | Novel compounds |
| US6887876B2 (en) | 2000-12-14 | 2005-05-03 | Ortho-Mcneil Pharmaceutical, Inc. | Benzamidine derivatives |
| CA2436263A1 (en) * | 2000-12-15 | 2002-06-20 | Astrazeneca Ab | New process for the preparation diaryl-4-amino-piperidinyl compounds |
| SE0101773D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101769D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101770D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101771D0 (sv) * | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| US7229994B2 (en) | 2001-05-18 | 2007-06-12 | Astrazeneca Ab | 4(phenyl-piperazinyl-methyl) benzamide derivatives and their use for the treatment of pain anxiety or gastrointestinal disorders |
| ATE347549T1 (de) | 2001-10-15 | 2006-12-15 | Janssen Pharmaceutica Nv | Neue substituierte 4-phenyl-4-(1h-imidazo-2-yl)- piperidin-derivate und ihre anwendung als selective delta-opioid-agonisten |
| EP1507756B1 (en) | 2002-05-24 | 2015-07-22 | Millennium Pharmaceuticals, Inc. | Ccr9 inhibitors and methods of use thereof |
| SE0203300D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203303D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203302D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| US7741519B2 (en) | 2007-04-23 | 2010-06-22 | Chemocentryx, Inc. | Bis-aryl sulfonamides |
| US7420055B2 (en) | 2002-11-18 | 2008-09-02 | Chemocentryx, Inc. | Aryl sulfonamides |
| US7227035B2 (en) | 2002-11-18 | 2007-06-05 | Chemocentryx | Bis-aryl sulfonamides |
| EP1562940B1 (en) | 2002-11-18 | 2007-05-30 | ChemoCentryx Inc | Aryl sulfonamides |
| ATE407117T1 (de) * | 2003-01-16 | 2008-09-15 | Acadia Pharm Inc | Selektive serotonin 2a/2c inverse rezeptoragonisten als therapeutika für neurodegenerative erkrankungen |
| AU2004253898A1 (en) | 2003-06-27 | 2005-01-13 | Janssen Pharmaceutica N.V. | Tricyclic delta opioid modulators |
| WO2005075472A1 (en) | 2004-02-03 | 2005-08-18 | Janssen Pharmaceutica, N.V. | 3-(diheteroarylnethylene)-8-azabicyclo[3.2.1]octane and 3-(aryl)(heteroaryl)methylene)-8-azabicyclo[3.2.1]octane derivatives |
| MX2007001240A (es) | 2004-08-02 | 2007-03-23 | Astrazeneca Ab | Derivados de diarilmetil-piperazina, preparaciones y usos de las mismas. |
| EA200700403A1 (ru) * | 2004-08-05 | 2007-08-31 | Янссен Фармацевтика Н.В. | ТРИЦИКЛИЧЕСКИЕ δ-ОПИОИДНЫЕ МОДУЛЯТОРЫ |
| MX2007007627A (es) * | 2004-12-22 | 2008-01-28 | Johnson & Johnson | Moduladores delta-opioides triciclicos. |
| BRPI0519198A2 (pt) * | 2004-12-22 | 2008-12-30 | Janssen Pharmaceutica Nv | moduladores de delta-opiàide tricÍclicos |
| KR20070092293A (ko) * | 2004-12-22 | 2007-09-12 | 얀센 파마슈티카 엔.브이. | 트리사이클릭 δ-오피오이드 모듈레이터 |
| US7432257B2 (en) * | 2005-01-06 | 2008-10-07 | Janssen Pharmaceutica N.V. | Piperdinyl-phenoxazine and phenothiazine derivatives as δ-opioid modulators |
| TWI449692B (zh) | 2005-05-13 | 2014-08-21 | Otsuka Pharma Co Ltd | 吡咯烷化合物(三) |
| EP1896467B1 (en) * | 2005-06-16 | 2010-12-01 | Janssen Pharmaceutica NV | Tricyclic opioid modulators |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4091096A (en) * | 1976-03-19 | 1978-05-23 | Eli Lilly And Company | Dinitroanilines for the control of phytopathogens |
| EG12406A (en) * | 1976-08-12 | 1979-03-31 | Janssen Pharmaceutica Nv | Process for preparing of novel n-aryl-n-(1-l-4-piperidinyl)-arylacetamides |
| SE441448B (sv) * | 1977-05-23 | 1985-10-07 | Pfizer | Sett att framstella hexahydro-gamma-karbolinforeningar |
| DE3200304A1 (de) * | 1981-01-16 | 1982-08-26 | Sandoz-Patent-GmbH, 7850 Lörrach | 3-aminopropoxyaryl-derivate, ihre herstellung und sie enthaltende arzneimittel |
| DE3563964D1 (en) * | 1984-10-16 | 1988-09-01 | Synthelabo | Piperidine derivatives, their preparation and their therapeutical application |
| KR940003491B1 (ko) | 1989-08-10 | 1994-04-23 | 리히터 게데온 베기에스제티 기아르 알.티 | 4,4-이중 치환된 피페리딘 유도체와 그 제조방법 및 상기 화합물을 함유하는 약제학적 조성물 |
| YU150489A (sh) | 1989-08-10 | 1992-12-21 | W.L. Gore & Co. Gmbh. | Uređaj za ispitivanje odevnih predmeta na nepromočivost |
| SE8904298D0 (sv) * | 1989-12-21 | 1989-12-21 | Astra Ab | New compounds |
| GB9202238D0 (en) * | 1992-02-03 | 1992-03-18 | Wellcome Found | Compounds |
| US5854245A (en) * | 1996-06-28 | 1998-12-29 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| SE9604786D0 (sv) * | 1996-12-20 | 1996-12-20 | Astra Pharma Inc | New compounds |
| TW548271B (en) * | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| AU2009799A (en) * | 1997-12-24 | 1999-07-19 | Ortho-Mcneil Pharmaceutical, Inc. | 4-(aryl(piperidin-4-yl)) aminobenzamides which bind to the delta-opioid receptor |
| AU756983B2 (en) | 1998-03-10 | 2003-01-30 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| US6436959B1 (en) | 1998-12-23 | 2002-08-20 | Ortho-Mcneil Pharmaceutical, Inc. | 4-[aryl(piperidin-4-yl)]aminobenzamides |
-
1996
- 1996-12-20 SE SE9604786A patent/SE9604786D0/xx unknown
-
1997
- 1997-09-12 UA UA99074131A patent/UA54481C2/uk unknown
- 1997-12-09 WO PCT/SE1997/002051 patent/WO1998028270A1/en not_active Ceased
- 1997-12-09 ES ES97950539T patent/ES2219783T3/es not_active Expired - Lifetime
- 1997-12-09 CZ CZ992200A patent/CZ220099A3/cs unknown
- 1997-12-09 US US09/029,468 patent/US6153626A/en not_active Expired - Lifetime
- 1997-12-09 ZA ZA9711049A patent/ZA9711049B/xx unknown
- 1997-12-09 BR BR9713785-5A patent/BR9713785A/pt unknown
- 1997-12-09 CA CA002274117A patent/CA2274117A1/en not_active Abandoned
- 1997-12-09 NZ NZ336028A patent/NZ336028A/en unknown
- 1997-12-09 CN CNA2004100324204A patent/CN1539824A/zh active Pending
- 1997-12-09 JP JP52867098A patent/JP2001507021A/ja not_active Ceased
- 1997-12-09 PT PT97950539T patent/PT946510E/pt unknown
- 1997-12-09 IL IL13053697A patent/IL130536A0/xx unknown
- 1997-12-09 AU AU53513/98A patent/AU738002B2/en not_active Ceased
- 1997-12-09 EP EP04002901A patent/EP1428821A1/en not_active Withdrawn
- 1997-12-09 RU RU99115746/04A patent/RU2193030C2/ru not_active IP Right Cessation
- 1997-12-09 EE EEP199900261A patent/EE03966B1/xx not_active IP Right Cessation
- 1997-12-09 EP EP97950539A patent/EP0946510B1/en not_active Expired - Lifetime
- 1997-12-09 CN CNB971808376A patent/CN1154635C/zh not_active Expired - Fee Related
- 1997-12-09 DE DE69729115T patent/DE69729115T2/de not_active Expired - Fee Related
- 1997-12-09 SK SK763-99A patent/SK283300B6/sk unknown
- 1997-12-09 ID IDW990536A patent/ID21662A/id unknown
- 1997-12-09 HU HU0000613A patent/HUP0000613A3/hu unknown
- 1997-12-09 DK DK97950539T patent/DK0946510T3/da active
- 1997-12-09 KR KR1019997005586A patent/KR20000069600A/ko not_active Ceased
- 1997-12-09 PL PL97334370A patent/PL188945B1/pl not_active IP Right Cessation
- 1997-12-09 AT AT97950539T patent/ATE266638T1/de not_active IP Right Cessation
- 1997-12-09 TR TR1999/01411T patent/TR199901411T2/xx unknown
- 1997-12-19 AR ARP970106076A patent/AR010378A1/es active IP Right Grant
- 1997-12-19 MY MYPI97006174A patent/MY132705A/en unknown
-
1999
- 1999-06-11 IS IS5078A patent/IS5078A/is unknown
- 1999-06-18 NO NO19993023A patent/NO313632B1/no unknown
-
2000
- 2000-08-25 US US09/645,565 patent/US6399635B1/en not_active Expired - Fee Related
-
2002
- 2002-04-15 US US10/121,683 patent/US6710179B2/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4754068B2 (ja) * | 1997-12-24 | 2011-08-24 | オーソ−マクニール・フアーマシユーチカル・インコーポレーテツド | δ−オピオイドレセプターに結合する4−[アリール(ピペリジン−4−イル)]アミノベンズアミド類 |
| JP2010095543A (ja) * | 1998-03-10 | 2010-04-30 | Research Triangle Inst | 新規なオピエート化合物、その調製法及び使用法 |
| JP2005525381A (ja) * | 2002-03-13 | 2005-08-25 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ヒストンデアセチラーゼの新規な阻害剤としてのアミノ誘導体 |
| JP2008137997A (ja) * | 2006-11-10 | 2008-06-19 | Otsuka Pharmaceut Co Ltd | 医薬 |
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