AU2004249178B2 - Substituted piperidine compounds and methods of their use - Google Patents
Substituted piperidine compounds and methods of their use Download PDFInfo
- Publication number
- AU2004249178B2 AU2004249178B2 AU2004249178A AU2004249178A AU2004249178B2 AU 2004249178 B2 AU2004249178 B2 AU 2004249178B2 AU 2004249178 A AU2004249178 A AU 2004249178A AU 2004249178 A AU2004249178 A AU 2004249178A AU 2004249178 B2 AU2004249178 B2 AU 2004249178B2
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- AU
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- Prior art keywords
- alkyl
- optionally substituted
- groups
- compound according
- aryl
- 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
- 238000000034 method Methods 0.000 title claims description 77
- 150000003053 piperidines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 237
- 125000000217 alkyl group Chemical group 0.000 claims description 178
- 125000003118 aryl group Chemical group 0.000 claims description 140
- -1 cycloalkenylalkyl Chemical group 0.000 claims description 108
- 125000005843 halogen group Chemical group 0.000 claims description 106
- 125000001424 substituent group Chemical group 0.000 claims description 96
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 69
- 125000003545 alkoxy group Chemical group 0.000 claims description 62
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 62
- 125000003342 alkenyl group Chemical group 0.000 claims description 54
- 125000001589 carboacyl group Chemical group 0.000 claims description 54
- 239000000203 mixture Substances 0.000 claims description 53
- 238000011282 treatment Methods 0.000 claims description 52
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 50
- 230000000694 effects Effects 0.000 claims description 45
- 108090000137 Opioid Receptors Proteins 0.000 claims description 40
- 102000003840 Opioid Receptors Human genes 0.000 claims description 39
- 125000000304 alkynyl group Chemical group 0.000 claims description 31
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 30
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 27
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 24
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 20
- 210000003169 central nervous system Anatomy 0.000 claims description 20
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 19
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- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000004423 acyloxy group Chemical group 0.000 claims description 16
- 125000003435 aroyl group Chemical group 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 claims description 8
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
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- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 claims description 5
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- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 claims description 4
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 4
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- IDBPHNDTYPBSNI-UHFFFAOYSA-N N-(1-(2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)ethyl)-4-(methoxymethyl)-4-piperidyl)propionanilide Chemical compound C1CN(CCN2C(N(CC)N=N2)=O)CCC1(COC)N(C(=O)CC)C1=CC=CC=C1 IDBPHNDTYPBSNI-UHFFFAOYSA-N 0.000 claims description 4
- UQCNKQCJZOAFTQ-ISWURRPUSA-N Oxymorphone Chemical compound O([C@H]1C(CC[C@]23O)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O UQCNKQCJZOAFTQ-ISWURRPUSA-N 0.000 claims description 4
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- RMRJXGBAOAMLHD-IHFGGWKQSA-N buprenorphine Chemical compound C([C@]12[C@H]3OC=4C(O)=CC=C(C2=4)C[C@@H]2[C@]11CC[C@]3([C@H](C1)[C@](C)(O)C(C)(C)C)OC)CN2CC1CC1 RMRJXGBAOAMLHD-IHFGGWKQSA-N 0.000 claims description 4
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Classifications
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- 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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- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P1/10—Laxatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
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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]
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- A—HUMAN NECESSITIES
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- 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
-
- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/59—Hydrogenated pyridine rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Addiction (AREA)
- Biochemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Molecular Biology (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
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| US10/462,507 | 2003-06-16 | ||
| US10/462,507 US6992090B2 (en) | 2003-06-16 | 2003-06-16 | Substituted piperidine compounds and methods of their use |
| PCT/US2004/018905 WO2004112704A2 (en) | 2003-06-16 | 2004-06-15 | Substituted piperidine compounds and methods of their use |
Related Child Applications (1)
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| AU2011203123A Division AU2011203123A1 (en) | 2003-06-16 | 2011-06-28 | Substituted piperidine compounds and methods of their use |
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| AU2004249178A1 AU2004249178A1 (en) | 2004-12-29 |
| AU2004249178B2 true AU2004249178B2 (en) | 2011-03-31 |
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| AU2004249178A Ceased AU2004249178B2 (en) | 2003-06-16 | 2004-06-15 | Substituted piperidine compounds and methods of their use |
Country Status (8)
| Country | Link |
|---|---|
| US (3) | US6992090B2 (https=) |
| EP (2) | EP1638565A4 (https=) |
| JP (1) | JP4889487B2 (https=) |
| CN (1) | CN1826115B (https=) |
| AU (1) | AU2004249178B2 (https=) |
| BR (1) | BRPI0411585A (https=) |
| CA (1) | CA2529524A1 (https=) |
| WO (1) | WO2004112704A2 (https=) |
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| US7381721B2 (en) | 2003-03-17 | 2008-06-03 | Adolor Corporation | Substituted piperidine compounds |
| US6992090B2 (en) * | 2003-06-16 | 2006-01-31 | Adolor Corporation | Substituted piperidine compounds and methods of their use |
| US8131026B2 (en) | 2004-04-16 | 2012-03-06 | Validity Sensors, Inc. | Method and apparatus for fingerprint image reconstruction |
| WO2006041780A1 (en) | 2004-10-04 | 2006-04-20 | Validity Sensors, Inc. | Fingerprint sensing assemblies comprising a substrate |
| MY145633A (en) | 2006-03-01 | 2012-03-15 | Theravance Inc | 8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| US20100222345A1 (en) * | 2006-08-09 | 2010-09-02 | Caroline Jean Diaz | Novel compounds as antagonists or inverse agonists for opioid receptors |
| TWI409067B (zh) | 2007-02-28 | 2013-09-21 | Theravance Inc | ８-氮雜雙環〔３．２．１〕辛烷化合物之結晶型 |
| CA2688570A1 (en) * | 2007-05-31 | 2008-12-04 | F.P.L. Pharma Inc. | Compositions for prevention or treatment of anorexia-cachexia syndrome and uses thereof |
| JP2010536749A (ja) * | 2007-08-15 | 2010-12-02 | シェーリング コーポレイション | １１β−ヒドロキシステロイドデヒドロゲナーゼＩ型を阻害するのに有用な置換二環式ピペリジニルスルホンアミドおよびピペラジニルスルホンアミド |
| ATE502939T1 (de) | 2007-08-27 | 2011-04-15 | Theravance Inc | Disubstituierte alkyl-8-azabicycloä3.2.1üoktan- verbindungen als mu-opioid-rezeptorantagonisten |
| ES2390195T3 (es) * | 2007-08-27 | 2012-11-07 | Theravance, Inc. | Compuestos de amidoalquil-8-azabiciclo(3,2,1)octano, como antagonistas del receptor opioide mu |
| TWI423801B (zh) * | 2007-08-27 | 2014-01-21 | Theravance Inc | 作為μ類鴉片受體拮抗劑之８－氮雜雙環〔３．２．１〕辛基－２－羥基苯甲醯胺化合物 |
| EP2195313B1 (en) * | 2007-08-27 | 2014-04-02 | Theravance, Inc. | Heteroarylalkyl-8-azabicyclo[3.2.1]octane compounds as mu opioid receptor antagonists |
| JP2011500686A (ja) * | 2007-10-18 | 2011-01-06 | アイコ バイオテクノロジー | オピオイドと中性アンタゴニストを用いる組合せ鎮痛剤 |
| US8748448B2 (en) | 2007-10-18 | 2014-06-10 | Aiko Biotechnology | Combination analgesic employing opioid agonist and neutral antagonist |
| JP5757864B2 (ja) | 2008-05-20 | 2015-08-05 | ニューロジェシックス， インコーポレイテッド | 水溶性アセトアミノフェン類似体 |
| EP2291084A4 (en) | 2008-05-20 | 2012-04-25 | Neurogesx Inc | CARBONATE PRODRUGS AND METHOD FOR THEIR USE |
| US20100311782A1 (en) * | 2009-06-08 | 2010-12-09 | Adolor Corporation | Substituted piperidinylpropanoic acid compounds and methods of their use |
| WO2011161646A2 (en) | 2010-06-25 | 2011-12-29 | Ranbaxy Laboratories Limited | Process for the preparation of alvimopan or its pharmaceutically acceptable salt or solvate thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0506478A1 (en) * | 1991-03-29 | 1992-09-30 | Eli Lilly And Company | Piperidine derivatives |
| US5159081A (en) * | 1991-03-29 | 1992-10-27 | Eli Lilly And Company | Intermediates of peripherally selective n-carbonyl-3,4,4-trisubstituted piperidine opioid antagonists |
| US5434171A (en) * | 1993-12-08 | 1995-07-18 | Eli Lilly And Company | Preparation of 3,4,4-trisubstituted-piperidinyl-N-alkylcarboxylates and intermediates |
| WO2001037785A2 (en) * | 1999-11-29 | 2001-05-31 | Adolor Corporation | Novel methods and compositions involving opioids and antagonists thereof |
| WO2001041705A2 (en) * | 1999-11-29 | 2001-06-14 | Adolor Corporation | Novel methods for the treatment and prevention of dizziness and pruritus |
| WO2002030896A1 (en) * | 2000-10-12 | 2002-04-18 | Ssp Co., Ltd. | 2,2-diphenylbutanamide derivatives and medicines containing the same |
| AU2003258146A1 (en) * | 2002-08-08 | 2004-02-25 | Adolor Corporation | Novel processes for the preparation of peripheral opioid antagonist compounds and intermediates thereto |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4191771A (en) * | 1974-09-06 | 1980-03-04 | Eli Lilly And Company | Analgesic method using 1,3,4-trisubstituted-4-arylpiperidines |
| US4115400A (en) | 1976-05-27 | 1978-09-19 | Eli Lilly And Company | 1-Azoniabicyclo[3.1.0]hexanes |
| US4176186A (en) | 1978-07-28 | 1979-11-27 | Boehringer Ingelheim Gmbh | Quaternary derivatives of noroxymorphone which relieve intestinal immobility |
| NZ191763A (en) * | 1978-10-13 | 1984-05-31 | Hoffmann La Roche | 7-beta-phenyl-quinolidines, intermediates and pharmaceutical compositions |
| US4931558A (en) * | 1983-09-21 | 1990-06-05 | Eli Lilly And Company | Processes for preparing intermediates of picenadol |
| US4891379A (en) | 1987-04-16 | 1990-01-02 | Kabushiki Kaisha Kobe Seikosho | Piperidine opioid antagonists |
| GB8803076D0 (en) | 1988-02-10 | 1988-03-09 | Erba Carlo Spa | 3'-deamino-4'-deoxy-4'-amino anthracyclines |
| US5250542A (en) | 1991-03-29 | 1993-10-05 | Eli Lilly And Company | Peripherally selective piperidine carboxylate opioid antagonists |
| US5270328A (en) | 1991-03-29 | 1993-12-14 | Eli Lilly And Company | Peripherally selective piperidine opioid antagonists |
| US5972954A (en) | 1997-11-03 | 1999-10-26 | Arch Development Corporation | Use of methylnaltrexone and related 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 |
| GB9912411D0 (en) * | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| US6451806B2 (en) * | 1999-09-29 | 2002-09-17 | Adolor Corporation | Methods and compositions involving opioids and antagonists thereof |
| MXPA02005336A (es) * | 1999-11-29 | 2003-01-28 | Adolor Corp | Metodos novedosos para el tratamiento y prevencion del ileo. |
| US20030100562A1 (en) * | 1999-11-30 | 2003-05-29 | Yudu Cheng | Diketopiperazine derivatives to inhibit thrombin |
| JP4340437B2 (ja) | 2000-10-31 | 2009-10-07 | レンセラール ポリテクニック インスティチュート | ８−カルボキサミド−２，６−メタノ−３−ベンズアゾシン |
| US6974824B2 (en) | 2001-01-08 | 2005-12-13 | Research Triangle Institute | Kappa opioid receptor ligands |
| US7381721B2 (en) * | 2003-03-17 | 2008-06-03 | Adolor Corporation | Substituted piperidine compounds |
| US20040204453A1 (en) * | 2003-04-14 | 2004-10-14 | Pfizer Inc | 4-Phenyl-piperidine compounds and their use as modulators of opioid receptors |
| US6992090B2 (en) * | 2003-06-16 | 2006-01-31 | Adolor Corporation | Substituted piperidine compounds and methods of their use |
-
2003
- 2003-06-16 US US10/462,507 patent/US6992090B2/en not_active Expired - Fee Related
-
2004
- 2004-06-15 AU AU2004249178A patent/AU2004249178B2/en not_active Ceased
- 2004-06-15 EP EP04755219A patent/EP1638565A4/en not_active Withdrawn
- 2004-06-15 CA CA002529524A patent/CA2529524A1/en not_active Abandoned
- 2004-06-15 CN CN2004800194266A patent/CN1826115B/zh not_active Expired - Fee Related
- 2004-06-15 WO PCT/US2004/018905 patent/WO2004112704A2/en not_active Ceased
- 2004-06-15 EP EP11166283A patent/EP2394992A3/en not_active Withdrawn
- 2004-06-15 BR BRPI0411585-6A patent/BRPI0411585A/pt not_active IP Right Cessation
- 2004-06-15 JP JP2006517257A patent/JP4889487B2/ja not_active Expired - Fee Related
-
2005
- 2005-09-01 US US11/217,528 patent/US7820827B2/en not_active Expired - Fee Related
-
2010
- 2010-10-05 US US12/897,824 patent/US8288546B2/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0506478A1 (en) * | 1991-03-29 | 1992-09-30 | Eli Lilly And Company | Piperidine derivatives |
| US5159081A (en) * | 1991-03-29 | 1992-10-27 | Eli Lilly And Company | Intermediates of peripherally selective n-carbonyl-3,4,4-trisubstituted piperidine opioid antagonists |
| US5434171A (en) * | 1993-12-08 | 1995-07-18 | Eli Lilly And Company | Preparation of 3,4,4-trisubstituted-piperidinyl-N-alkylcarboxylates and intermediates |
| WO2001037785A2 (en) * | 1999-11-29 | 2001-05-31 | Adolor Corporation | Novel methods and compositions involving opioids and antagonists thereof |
| WO2001041705A2 (en) * | 1999-11-29 | 2001-06-14 | Adolor Corporation | Novel methods for the treatment and prevention of dizziness and pruritus |
| WO2002030896A1 (en) * | 2000-10-12 | 2002-04-18 | Ssp Co., Ltd. | 2,2-diphenylbutanamide derivatives and medicines containing the same |
| AU2003258146A1 (en) * | 2002-08-08 | 2004-02-25 | Adolor Corporation | Novel processes for the preparation of peripheral opioid antagonist compounds and intermediates thereto |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2529524A1 (en) | 2004-12-29 |
| US8288546B2 (en) | 2012-10-16 |
| AU2004249178A1 (en) | 2004-12-29 |
| JP2006527775A (ja) | 2006-12-07 |
| CN1826115B (zh) | 2010-05-26 |
| US7820827B2 (en) | 2010-10-26 |
| WO2004112704A2 (en) | 2004-12-29 |
| JP4889487B2 (ja) | 2012-03-07 |
| WO2004112704A3 (en) | 2005-09-15 |
| EP2394992A3 (en) | 2012-03-21 |
| BRPI0411585A (pt) | 2006-08-08 |
| EP1638565A4 (en) | 2008-07-23 |
| CN1826115A (zh) | 2006-08-30 |
| US20060089383A1 (en) | 2006-04-27 |
| US20110034417A1 (en) | 2011-02-10 |
| US20040254218A1 (en) | 2004-12-16 |
| EP2394992A2 (en) | 2011-12-14 |
| US6992090B2 (en) | 2006-01-31 |
| EP1638565A2 (en) | 2006-03-29 |
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