JP4754068B2 - 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 - Google Patents
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 Download PDFInfo
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- JP4754068B2 JP4754068B2 JP2000526490A JP2000526490A JP4754068B2 JP 4754068 B2 JP4754068 B2 JP 4754068B2 JP 2000526490 A JP2000526490 A JP 2000526490A JP 2000526490 A JP2000526490 A JP 2000526490A JP 4754068 B2 JP4754068 B2 JP 4754068B2
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- Prior art keywords
- alkyl
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- compound
- propyl
- butyl
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- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 title claims abstract description 16
- 108700023159 delta Opioid Receptors Proteins 0.000 title claims abstract description 16
- 102000048124 delta Opioid Receptors Human genes 0.000 title claims abstract description 16
- PXBFMLJZNCDSMP-UHFFFAOYSA-N 2-Aminobenzamide Chemical class NC(=O)C1=CC=CC=C1N PXBFMLJZNCDSMP-UHFFFAOYSA-N 0.000 title abstract description 4
- 125000003118 aryl group Chemical group 0.000 title abstract description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 title abstract description 3
- 230000027455 binding Effects 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 42
- 239000003814 drug Substances 0.000 claims abstract description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 18
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 17
- 229940079593 drug Drugs 0.000 claims abstract description 15
- 206010012735 Diarrhoea Diseases 0.000 claims abstract description 7
- 208000007882 Gastritis Diseases 0.000 claims abstract description 7
- 239000002260 anti-inflammatory agent Substances 0.000 claims abstract description 7
- 229940121363 anti-inflammatory agent Drugs 0.000 claims abstract description 7
- 239000002327 cardiovascular agent Substances 0.000 claims abstract description 7
- 229940125692 cardiovascular agent Drugs 0.000 claims abstract description 7
- 229960003444 immunosuppressant agent Drugs 0.000 claims abstract description 7
- 239000003018 immunosuppressive agent Substances 0.000 claims abstract description 7
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 7
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 claims abstract description 7
- 208000007848 Alcoholism Diseases 0.000 claims abstract description 6
- 206010013654 Drug abuse Diseases 0.000 claims abstract description 6
- 206010001584 alcohol abuse Diseases 0.000 claims abstract description 6
- 208000025746 alcohol use disease Diseases 0.000 claims abstract description 6
- 208000011117 substance-related disease Diseases 0.000 claims abstract description 6
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims abstract description 3
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 40
- -1 cyano, amino Chemical group 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 239000003446 ligand Substances 0.000 claims description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000001475 halogen functional group Chemical group 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 208000028017 Psychotic disease Diseases 0.000 claims description 5
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 4
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 230000000202 analgesic effect Effects 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000036407 pain Effects 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 2
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 125000006594 (C1-C3) alkylsulfony group Chemical group 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 230000000561 anti-psychotic effect Effects 0.000 claims 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 claims 1
- 201000009032 substance abuse Diseases 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 239000000556 agonist Substances 0.000 abstract description 5
- 229940035676 analgesics Drugs 0.000 abstract description 5
- 239000005557 antagonist Substances 0.000 abstract description 5
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- 229940044601 receptor agonist Drugs 0.000 abstract description 4
- 239000000018 receptor agonist Substances 0.000 abstract description 4
- 208000020016 psychiatric disease Diseases 0.000 abstract 1
- 239000002464 receptor antagonist Substances 0.000 abstract 1
- 229940044551 receptor antagonist Drugs 0.000 abstract 1
- 238000000034 method Methods 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
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- 239000007983 Tris buffer Substances 0.000 description 7
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- 210000004556 brain Anatomy 0.000 description 6
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- IWNWTTFSRFJZDY-UHFFFAOYSA-N n-(3-methoxyphenyl)-1-propylpiperidin-4-amine Chemical compound C1CN(CCC)CCC1NC1=CC=CC(OC)=C1 IWNWTTFSRFJZDY-UHFFFAOYSA-N 0.000 description 6
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- 125000001424 substituent group Chemical group 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
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- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 4
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
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- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 4
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- NCBZRJODKRCREW-UHFFFAOYSA-N m-anisidine Chemical compound COC1=CC=CC(N)=C1 NCBZRJODKRCREW-UHFFFAOYSA-N 0.000 description 4
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- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
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- ZEHGKSPCAMLJDC-UHFFFAOYSA-M acetylcholine bromide Chemical compound [Br-].CC(=O)OCC[N+](C)(C)C ZEHGKSPCAMLJDC-UHFFFAOYSA-M 0.000 description 3
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- JFPHICCUJHJABY-UHFFFAOYSA-N n,n-diethyl-4-(3-hydroxy-n-(1-propylpiperidin-4-yl)anilino)benzamide Chemical compound C1CN(CCC)CCC1N(C=1C=C(O)C=CC=1)C1=CC=C(C(=O)N(CC)CC)C=C1 JFPHICCUJHJABY-UHFFFAOYSA-N 0.000 description 3
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- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
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- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 1
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- YGDZKYYCJUNORF-UHFFFAOYSA-N 1-propylpiperidin-4-one Chemical compound CCCN1CCC(=O)CC1 YGDZKYYCJUNORF-UHFFFAOYSA-N 0.000 description 1
- VTDIWMPYBAVEDY-UHFFFAOYSA-N 1-propylpiperidine Chemical compound CCCN1CCCCC1 VTDIWMPYBAVEDY-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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- A61P9/00—Drugs for disorders of the cardiovascular system
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
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- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Transplantation (AREA)
- Rheumatology (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6879497P | 1997-12-24 | 1997-12-24 | |
| US60/068,794 | 1997-12-24 | ||
| PCT/US1998/027350 WO1999033806A1 (en) | 1997-12-24 | 1998-12-23 | 4-[aryl(piperidin-4-yl)] aminobenzamides which bind to the delta-opioid receptor |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2001527068A JP2001527068A (ja) | 2001-12-25 |
| JP2001527068A5 JP2001527068A5 (https=) | 2006-01-12 |
| JP4754068B2 true JP4754068B2 (ja) | 2011-08-24 |
Family
ID=22084747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000526490A Expired - Lifetime JP4754068B2 (ja) | 1997-12-24 | 1998-12-23 | 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 |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP1049676B1 (https=) |
| JP (1) | JP4754068B2 (https=) |
| AT (1) | ATE306472T1 (https=) |
| AU (1) | AU2009799A (https=) |
| CA (1) | CA2316341A1 (https=) |
| DE (1) | DE69831876T2 (https=) |
| DK (1) | DK1049676T3 (https=) |
| ES (1) | ES2251121T3 (https=) |
| TW (1) | TW476755B (https=) |
| WO (1) | WO1999033806A1 (https=) |
| ZA (1) | ZA9811842B (https=) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9504661D0 (sv) | 1995-12-22 | 1995-12-22 | Astra Pharma Inc | New compounds |
| US6974825B1 (en) | 1996-12-20 | 2005-12-13 | Astrazeneca Canada Inc. | Compounds with analgesic effect |
| TW548271B (en) | 1996-12-20 | 2003-08-21 | Astra Pharma Inc | Novel piperidine derivatives having an exocyclic double bond with analgesic effects |
| SE9604786D0 (sv) | 1996-12-20 | 1996-12-20 | Astra Pharma Inc | New compounds |
| EP1512683B1 (en) * | 1998-03-10 | 2011-08-31 | Research Triangle Institute | Novel opiate compounds, methods of making and methods of use |
| US6900228B1 (en) | 1998-03-10 | 2005-05-31 | Research Triangle Institute | Opiate compounds, methods of making and methods of use |
| JP2003500392A (ja) * | 1999-05-25 | 2003-01-07 | セプラコール， インク． | 複素環式鎮痛性化合物およびその使用方法 |
| US6635661B2 (en) | 2000-05-25 | 2003-10-21 | Sepracor Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| US7361666B2 (en) | 1999-05-25 | 2008-04-22 | Sepracor, Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| US6677332B1 (en) | 1999-05-25 | 2004-01-13 | Sepracor, Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| US6645980B1 (en) | 2000-05-25 | 2003-11-11 | Sepracor Inc. | Heterocyclic analgesic compounds and methods of use thereof |
| 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 |
| JP2003518119A (ja) * | 1999-12-22 | 2003-06-03 | 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 | ４−［アリール（８−アザビシクロ［３．２．１］オクタン−３−イル）］アミノ安息香酸誘導体 |
| SE0001208D0 (sv) * | 2000-04-04 | 2000-04-04 | Astrazeneca Canada Inc | Novel compounds |
| SE0001209D0 (sv) | 2000-04-04 | 2000-04-04 | Astrazeneca Canada Inc | Novel compounds |
| SE0001207D0 (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 |
| IL155995A0 (en) | 2000-12-15 | 2003-12-23 | Astrazeneca Ab | New process for the preparation of diaryl-4-amino-piperidinyl compounds |
| US6699890B2 (en) * | 2000-12-22 | 2004-03-02 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| US7205320B2 (en) | 2001-01-22 | 2007-04-17 | Memory Pharmaceuticals Corp. | Phosphodiesterase 4 inhibitors |
| US7153871B2 (en) | 2001-01-22 | 2006-12-26 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors, including aminoindazole and aminobenzofuran analogs |
| MXPA03007261A (es) * | 2001-02-14 | 2006-03-09 | Abbott Lab | Moduladores del receptor de glucocorticoides. |
| SE0101773D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| DK1395567T3 (da) | 2001-05-18 | 2009-04-06 | Astrazeneca Ab | 4-(phenylpiperazinylmethyl)-benzamidderivater og deres anvendelse til behandling af smerte, angst eller mavetarmslidelser |
| SE0101769D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101766D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101765D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101771D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101768D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0101770D0 (sv) | 2001-05-18 | 2001-05-18 | Astrazeneca Ab | Novel compounds |
| SE0103313D0 (sv) | 2001-10-03 | 2001-10-03 | Astrazeneca Ab | Novel compounds |
| EP1539697A1 (en) | 2002-07-19 | 2005-06-15 | Memory Pharmaceutical Corporation | Phosphodiesterase 4 inhibitors, including n-substituted aniline and diphenylamine analogs |
| RU2354648C2 (ru) | 2002-07-19 | 2009-05-10 | Мемори Фармасьютиклз Корпорейшн | Соединения 6-амино-1н-индазола и 4-аминобензофурана в качестве ингибиторов фосфодиэстеразы 4 |
| ATE387443T1 (de) | 2002-10-15 | 2008-03-15 | Janssen Pharmaceutica Nv | Substituierte aminochinuclidin verbindungen und deren verwendung als delta-opioid rezeptor liganden |
| WO2004035541A1 (en) * | 2002-10-15 | 2004-04-29 | Janssen Pharmaceutica, N.V. | Benzyl substituted (piperidin-4-yl) aminobenzamido derivatives as delta-opiod receptor modulators |
| SE0203302D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203303D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| SE0203300D0 (sv) | 2002-11-07 | 2002-11-07 | Astrazeneca Ab | Novel Compounds |
| AU2003295656B2 (en) | 2002-11-19 | 2010-11-11 | Memory Pharmaceuticals Corporation | Pyridine N-oxide compounds as phosphodiesterase 4 inhibitors |
| EP1613597B1 (en) | 2003-03-07 | 2007-11-07 | Eli Lilly and Company | 6-substituted nicotinamide derivatives as opioid receptor antagonists |
| US7589103B2 (en) | 2003-06-27 | 2009-09-15 | Janssen Pharmaceutica N.V. | Tricyclic-bridged piperidinylidene derivatives as 8-opioid modulators |
| CA2549009A1 (en) * | 2003-12-12 | 2005-07-07 | Eli Lilly And Company | Opioid receptor antagonists |
| EP1735268B1 (en) | 2004-03-15 | 2012-02-15 | Eli Lilly And Company | Opioid receptor antagonists |
| DK1781631T3 (da) | 2004-08-02 | 2012-05-14 | Astrazeneca Ab | Diarylmethylpiperazinderivater, præparater dermed og anvendelser deraf |
| EP1910353A1 (en) | 2004-08-05 | 2008-04-16 | Janssen Pharmaceutica N.V. | Tricyclic delta- opioid modulators |
| SE0402485D0 (sv) | 2004-10-13 | 2004-10-13 | Astrazeneca Ab | Polymorph of N,N-Diethyl-4-(3-Fluorophenyl-Piperidin-4-Ylidene-Methyl)-Benzamide Hydrochloride salt |
| ATE432279T1 (de) | 2004-12-22 | 2009-06-15 | Janssen Pharmaceutica Nv | Tricyclische delta-opioid-modulatoren |
| JP2008525483A (ja) | 2004-12-22 | 2008-07-17 | 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 | 三環式δ−オピオイド調節剤 |
| KR20070104380A (ko) | 2005-01-06 | 2007-10-25 | 얀센 파마슈티카 엔.브이. | 트리사이클릭 δ-오피오이드 조절제 |
| ATE490251T1 (de) | 2005-06-16 | 2010-12-15 | Janssen Pharmaceutica Nv | Tricyclische opioidmodulatoren |
| JP2007099761A (ja) * | 2005-09-08 | 2007-04-19 | Mitsui Chemicals Inc | アミド誘導体ならびにその殺虫剤としての使用方法 |
| MY148880A (en) | 2006-10-20 | 2013-06-14 | Astrazeneca Ab | N-(2-hydroxyethyl)-n-methyl-4-(quinolin-8-yl(1-(thiazol-4-ylmethyl)piperidin-4-ylidene)methyl)benzamide, the process of making it as well as its use for the treatment of pain, anxiety and depression |
| JP5781527B2 (ja) * | 2009-10-30 | 2015-09-24 | ヤンセン ファーマシューティカ エヌ．ベー． | ４−置換−２−フェノキシ−フェニルアミンデルオピオイド受容体調節因子 |
| CN113979997A (zh) * | 2021-11-12 | 2022-01-28 | 中国科学院昆明植物研究所 | N,n-(4-哌啶基、芳基)-3-氨基苯酚类衍生物及其药物组合物和其应用 |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02300167A (ja) * | 1989-02-15 | 1990-12-12 | Glaxo Inc | 鎮痛剤として用いられるｎ―フエニル―ｎ―（４―ピペリジニル）アミド |
| JPH07503247A (ja) * | 1992-02-03 | 1995-04-06 | デルタ ファーマソウティカルズ，インコーポレイテッド | オピオイドジアリールメチルピペラジンおよびピペリジン |
| JPH11505237A (ja) * | 1995-05-19 | 1999-05-18 | スミスクライン・ビーチャム・ソシエタ・ペル・アチオニ | ジアリールジアミン誘導体およびそれらのデルタオピオイド（アント）−アゴニストとしての使用 |
| JPH11512413A (ja) * | 1995-09-15 | 1999-10-26 | スミスクライン・ビーチャム・ソシエタ・ペル・アチオニ | ジアリールアルケニルアミン誘導体 |
| JP2000502679A (ja) * | 1995-12-22 | 2000-03-07 | アストラ・フアーマ・インコーポレイテツド | 鎮痛作用を有する新規化合物 |
| JP2001507021A (ja) * | 1996-12-20 | 2001-05-29 | アストラ・フアーマ・インコーポレイテツド | 鎮痛作用を有する新規な化合物 |
-
1998
- 1998-12-23 WO PCT/US1998/027350 patent/WO1999033806A1/en not_active Ceased
- 1998-12-23 EP EP98964871A patent/EP1049676B1/en not_active Expired - Lifetime
- 1998-12-23 CA CA002316341A patent/CA2316341A1/en not_active Abandoned
- 1998-12-23 AT AT98964871T patent/ATE306472T1/de active
- 1998-12-23 DK DK98964871T patent/DK1049676T3/da active
- 1998-12-23 ES ES98964871T patent/ES2251121T3/es not_active Expired - Lifetime
- 1998-12-23 DE DE69831876T patent/DE69831876T2/de not_active Expired - Lifetime
- 1998-12-23 ZA ZA9811842A patent/ZA9811842B/xx unknown
- 1998-12-23 JP JP2000526490A patent/JP4754068B2/ja not_active Expired - Lifetime
- 1998-12-23 AU AU20097/99A patent/AU2009799A/en not_active Abandoned
-
1999
- 1999-02-11 TW TW087121577A patent/TW476755B/zh not_active IP Right Cessation
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02300167A (ja) * | 1989-02-15 | 1990-12-12 | Glaxo Inc | 鎮痛剤として用いられるｎ―フエニル―ｎ―（４―ピペリジニル）アミド |
| JPH07503247A (ja) * | 1992-02-03 | 1995-04-06 | デルタ ファーマソウティカルズ，インコーポレイテッド | オピオイドジアリールメチルピペラジンおよびピペリジン |
| JPH11505237A (ja) * | 1995-05-19 | 1999-05-18 | スミスクライン・ビーチャム・ソシエタ・ペル・アチオニ | ジアリールジアミン誘導体およびそれらのデルタオピオイド（アント）−アゴニストとしての使用 |
| JPH11512413A (ja) * | 1995-09-15 | 1999-10-26 | スミスクライン・ビーチャム・ソシエタ・ペル・アチオニ | ジアリールアルケニルアミン誘導体 |
| JP2000502679A (ja) * | 1995-12-22 | 2000-03-07 | アストラ・フアーマ・インコーポレイテツド | 鎮痛作用を有する新規化合物 |
| JP2001507021A (ja) * | 1996-12-20 | 2001-05-29 | アストラ・フアーマ・インコーポレイテツド | 鎮痛作用を有する新規な化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| ATE306472T1 (de) | 2005-10-15 |
| DK1049676T3 (da) | 2006-01-16 |
| AU2009799A (en) | 1999-07-19 |
| EP1049676B1 (en) | 2005-10-12 |
| JP2001527068A (ja) | 2001-12-25 |
| DE69831876D1 (de) | 2006-02-23 |
| DE69831876T2 (de) | 2006-07-27 |
| EP1049676A1 (en) | 2000-11-08 |
| ES2251121T3 (es) | 2006-04-16 |
| TW476755B (en) | 2002-02-21 |
| CA2316341A1 (en) | 1999-07-08 |
| WO1999033806A1 (en) | 1999-07-08 |
| ZA9811842B (en) | 2000-06-23 |
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