CA2683461A1 - Nouveaux ligands du recepteur vanilloide et leur utilisation pour la fabrication de medicaments - Google Patents
Nouveaux ligands du recepteur vanilloide et leur utilisation pour la fabrication de medicaments Download PDFInfo
- Publication number
- CA2683461A1 CA2683461A1 CA002683461A CA2683461A CA2683461A1 CA 2683461 A1 CA2683461 A1 CA 2683461A1 CA 002683461 A CA002683461 A CA 002683461A CA 2683461 A CA2683461 A CA 2683461A CA 2683461 A1 CA2683461 A1 CA 2683461A1
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- Prior art keywords
- butyl
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- 239000003814 drug Substances 0.000 title claims abstract description 49
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 20
- 108010062740 TRPV Cation Channels Proteins 0.000 title abstract description 35
- 102000011040 TRPV Cation Channels Human genes 0.000 title abstract description 32
- 239000003446 ligand Substances 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 173
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 312
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 283
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 279
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 277
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 223
- -1 monosubstituted tert-butyl residue Chemical group 0.000 claims description 151
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 150
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 147
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 147
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 147
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 115
- 239000000460 chlorine Substances 0.000 claims description 115
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 112
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 106
- 229920006395 saturated elastomer Polymers 0.000 claims description 100
- 125000001424 substituent group Chemical group 0.000 claims description 95
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- 239000000203 mixture Substances 0.000 claims description 89
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- 229910052731 fluorine Inorganic materials 0.000 claims description 84
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 83
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 83
- 229910052740 iodine Inorganic materials 0.000 claims description 81
- 125000000217 alkyl group Chemical group 0.000 claims description 80
- 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 claims description 76
- 229910052757 nitrogen Inorganic materials 0.000 claims description 70
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 52
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 claims description 52
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 50
- 125000001931 aliphatic group Chemical group 0.000 claims description 49
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 31
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 30
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 29
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- 229960002504 capsaicin Drugs 0.000 claims description 26
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- 125000001544 thienyl group Chemical group 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 22
- 239000012429 reaction media Substances 0.000 claims description 22
- 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 21
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- 125000003386 piperidinyl group Chemical group 0.000 claims description 20
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 20
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 20
- 238000005304 joining Methods 0.000 claims description 19
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 19
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 19
- 125000006591 (C2-C6) alkynylene group Chemical group 0.000 claims description 18
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 125000004122 cyclic group Chemical group 0.000 claims description 18
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 18
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 17
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000001624 naphthyl group Chemical group 0.000 claims description 17
- 125000003725 azepanyl group Chemical group 0.000 claims description 16
- 239000002585 base Substances 0.000 claims description 16
- 239000003054 catalyst Substances 0.000 claims description 16
- 125000002541 furyl group Chemical group 0.000 claims description 16
- 125000002757 morpholinyl group Chemical group 0.000 claims description 16
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
- 125000004193 piperazinyl group Chemical group 0.000 claims description 16
- 230000002265 prevention Effects 0.000 claims description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 15
- 125000000335 thiazolyl group Chemical group 0.000 claims description 15
- 229910052721 tungsten Inorganic materials 0.000 claims description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 14
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 239000011593 sulfur Substances 0.000 claims description 14
- 206010061218 Inflammation Diseases 0.000 claims description 13
- 230000004054 inflammatory process Effects 0.000 claims description 13
- 208000004296 neuralgia Diseases 0.000 claims description 13
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- 206010020853 Hypertonic bladder Diseases 0.000 claims description 12
- 208000009722 Overactive Urinary Bladder Diseases 0.000 claims description 12
- 229910052770 Uranium Inorganic materials 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 238000003556 assay Methods 0.000 claims description 12
- 125000005959 diazepanyl group Chemical group 0.000 claims description 12
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- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 12
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- 125000003566 oxetanyl group Chemical group 0.000 claims description 11
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 11
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- 125000005605 benzo group Chemical group 0.000 claims description 10
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- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 9
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- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 8
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 claims description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 8
- 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 claims description 8
- 238000011161 development Methods 0.000 claims description 8
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 8
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 8
- 125000001041 indolyl group Chemical group 0.000 claims description 8
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
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- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
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- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
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- SFYFRBVPZIXRSG-UHFFFAOYSA-N 2-(1,3-benzoxazol-7-yl)-n-[(4-tert-butylphenyl)methyl]propanamide Chemical compound C=1C=CC=2N=COC=2C=1C(C)C(=O)NCC1=CC=C(C(C)(C)C)C=C1 SFYFRBVPZIXRSG-UHFFFAOYSA-N 0.000 claims description 5
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- RLWGDRLXZSLGHV-UHFFFAOYSA-N 1-[[4-(2-aminoethoxy)-3-methoxyphenyl]methyl]-3-[(4-tert-butylphenyl)methyl]urea Chemical compound C1=C(OCCN)C(OC)=CC(CNC(=O)NCC=2C=CC(=CC=2)C(C)(C)C)=C1 RLWGDRLXZSLGHV-UHFFFAOYSA-N 0.000 claims description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D215/14—Radicals substituted by oxygen atoms
-
- 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
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Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102007018149A DE102007018149A1 (de) | 2007-04-16 | 2007-04-16 | Neue Vanilloid-Rezeptor Liganden und ihre Verwendung zur Herstellung von Arzneimitteln |
DE102007018149.5 | 2007-04-16 | ||
US12/103,667 US8084484B2 (en) | 2007-04-16 | 2008-04-15 | Vanilloid receptor ligands, pharmaceutical compositions containing them, process for making them, and use thereof for treating pain and other conditions |
EP2008002997 | 2008-04-15 | ||
US12/103,667 | 2008-04-15 | ||
EPPCT/EP2008/002997 | 2008-04-15 | ||
PCT/EP2008/003027 WO2008125342A2 (fr) | 2007-04-16 | 2008-04-16 | Nouveaux ligands du récepteur vanilloïde et leur utilisation pour la fabrication de médicaments |
Publications (1)
Publication Number | Publication Date |
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CA2683461A1 true CA2683461A1 (fr) | 2008-10-23 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CA002683461A Abandoned CA2683461A1 (fr) | 2007-04-16 | 2008-04-16 | Nouveaux ligands du recepteur vanilloide et leur utilisation pour la fabrication de medicaments |
Country Status (14)
Country | Link |
---|---|
JP (1) | JP2010523727A (fr) |
KR (1) | KR20100016593A (fr) |
CN (1) | CN101679370A (fr) |
AU (1) | AU2008238250B2 (fr) |
BR (1) | BRPI0810035A2 (fr) |
CA (1) | CA2683461A1 (fr) |
CO (1) | CO6241154A2 (fr) |
EC (1) | ECSP099692A (fr) |
IL (1) | IL201505A0 (fr) |
MX (1) | MX2009011149A (fr) |
NZ (1) | NZ580411A (fr) |
RU (1) | RU2498982C2 (fr) |
WO (1) | WO2008125342A2 (fr) |
ZA (1) | ZA200907099B (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10351535B2 (en) | 2013-12-20 | 2019-07-16 | Esteve Pharmaceuticals, S.A. | Piperazine derivatives having multimodal activity against pain |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102007018149A1 (de) | 2007-04-16 | 2008-10-23 | Grünenthal GmbH | Neue Vanilloid-Rezeptor Liganden und ihre Verwendung zur Herstellung von Arzneimitteln |
AR076752A1 (es) | 2009-05-07 | 2011-07-06 | Gruenenthal Chemie | Fenilureas y fenilamidas sustituidas como ligandos del receptor de vanilloides. |
US8946204B2 (en) | 2009-05-07 | 2015-02-03 | Gruenenthal Gmbh | Substituted phenylureas and phenylamides as vanilloid receptor ligands |
CA2842983A1 (fr) | 2011-07-26 | 2013-01-31 | Grunenthal Gmbh | Derives aza heterocycliques substitues |
EP2736899A1 (fr) | 2011-07-26 | 2014-06-04 | Grünenthal GmbH | Dérivés de carboxamide et d'urée aromatiques bicycliques substitués en tant que ligands de récepteur de vanilloïde |
WO2013068462A1 (fr) * | 2011-11-09 | 2013-05-16 | Grünenthal GmbH | Dérivés de carboxamide et d'urée à base de pyrazolyle substitué portant un fragment phényle remplacé par un groupe contenant n comme ligands des récepteurs vanilloïdes |
NZ629630A (en) * | 2012-03-05 | 2015-09-25 | Reddy’S Lab Ltd Dr | Substituted heterocyclic acetamides as kappa opioid receptor (kor) agonists |
CN107721919B (zh) * | 2017-10-30 | 2020-12-08 | 中国药科大学 | 苯基喹啉类trpv1拮抗剂及其制备方法和应用 |
KR102334947B1 (ko) * | 2020-04-22 | 2021-12-06 | 주식회사 제이맥켐 | Trpv1 길항제로서 벤즈이미다졸론계 시남아마이드 유도체 및 이를 유효성분으로 함유하는 통증의 치료 또는 예방용 약학적 조성물 |
RU2755206C1 (ru) | 2020-05-20 | 2021-09-14 | Федеральное государственное бюджетное учреждение науки Тихоокеанский институт биоорганической химии им. Г.Б. Елякова Дальневосточного отделения Российской академии наук (ТИБОХ ДВО РАН) | Средство пролонгированного анальгетического действия и лекарственный препарат на его основе |
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WO2003045920A1 (fr) * | 2001-11-27 | 2003-06-05 | Merck & Co., Inc. | Composes 4-aminoquinoleines |
CA2476936A1 (fr) * | 2002-02-20 | 2003-08-28 | Chih-Hung Lee | Composes azabicycliques fusionnes qui inhibent le recepteur (vr1) sous-type 1 du recepteur vanilloide |
GB0206876D0 (en) * | 2002-03-22 | 2002-05-01 | Merck Sharp & Dohme | Therapeutic agents |
US6933311B2 (en) * | 2003-02-11 | 2005-08-23 | Abbott Laboratories | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
CA2528143A1 (fr) * | 2003-04-29 | 2004-11-11 | Oxagen Limited | Methode de diagnostic d'une susceptibilite a des lesions osseuses |
SE0301446D0 (sv) * | 2003-05-16 | 2003-05-16 | Astrazeneca Ab | New Compounds |
RU2333198C2 (ru) * | 2003-06-12 | 2008-09-10 | Астеллас Фарма Инк. | Производные бензамида или фармацевтически приемлемые соли указанного производного, фармацевтическая композиция на их основе и применение |
US20050113576A1 (en) * | 2003-08-05 | 2005-05-26 | Chih-Hung Lee | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
GB0322016D0 (en) * | 2003-09-19 | 2003-10-22 | Merck Sharp & Dohme | New compounds |
US7683076B2 (en) * | 2003-11-08 | 2010-03-23 | Bayer Schering Pharma Aktiengesellschaft | Tetrahydro-quinolinylurea derivatives |
WO2005073193A1 (fr) * | 2004-01-23 | 2005-08-11 | Amgen Inc. | Ligands du recepteur vanilloide et leur utilisation dans des traitements |
DE102005023943A1 (de) * | 2005-05-20 | 2006-11-23 | Grünenthal GmbH | Pentafluorsulfanyl-substituierte Verbindung und deren Verwendung zur Herstellung von Arzneimitteln |
JP5165586B2 (ja) * | 2005-12-28 | 2013-03-21 | バーテックス ファーマシューティカルズ インコーポレイテッド | 嚢胞性線維症の処置のためのATP結合カセットトランスポーターのモジュレーターとしての、1−(ベンゾ[d][1,3]ジオキソール−5−イル)−N−(フェニル)シクロプロパン−カルボキサミド誘導体および関連化合物 |
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2008
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- 2008-04-16 MX MX2009011149A patent/MX2009011149A/es active IP Right Grant
- 2008-04-16 BR BRPI0810035A patent/BRPI0810035A2/pt not_active IP Right Cessation
- 2008-04-16 CN CN200880020483A patent/CN101679370A/zh active Pending
- 2008-04-16 RU RU2009142023/04A patent/RU2498982C2/ru not_active IP Right Cessation
- 2008-04-16 CA CA002683461A patent/CA2683461A1/fr not_active Abandoned
- 2008-04-16 AU AU2008238250A patent/AU2008238250B2/en not_active Ceased
- 2008-04-16 WO PCT/EP2008/003027 patent/WO2008125342A2/fr active Application Filing
- 2008-04-16 JP JP2010503397A patent/JP2010523727A/ja not_active Ceased
- 2008-04-16 KR KR1020097023887A patent/KR20100016593A/ko not_active Application Discontinuation
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2009
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- 2009-10-14 IL IL201505A patent/IL201505A0/en unknown
- 2009-10-16 EC EC2009009692A patent/ECSP099692A/es unknown
- 2009-10-22 CO CO09118505A patent/CO6241154A2/es active IP Right Grant
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US10351535B2 (en) | 2013-12-20 | 2019-07-16 | Esteve Pharmaceuticals, S.A. | Piperazine derivatives having multimodal activity against pain |
US10745361B2 (en) | 2013-12-20 | 2020-08-18 | Esteve Pharmaceuticals, S.A. | Piperazine derivatives having multimodal activity against pain |
Also Published As
Publication number | Publication date |
---|---|
WO2008125342A2 (fr) | 2008-10-23 |
ZA200907099B (en) | 2013-03-27 |
ECSP099692A (es) | 2009-11-30 |
JP2010523727A (ja) | 2010-07-15 |
MX2009011149A (es) | 2009-10-30 |
NZ580411A (en) | 2012-06-29 |
CO6241154A2 (es) | 2011-01-20 |
CN101679370A (zh) | 2010-03-24 |
BRPI0810035A2 (pt) | 2016-07-26 |
AU2008238250B2 (en) | 2013-01-24 |
KR20100016593A (ko) | 2010-02-12 |
WO2008125342A3 (fr) | 2009-01-15 |
AU2008238250A1 (en) | 2008-10-23 |
RU2498982C2 (ru) | 2013-11-20 |
IL201505A0 (en) | 2010-05-31 |
RU2009142023A (ru) | 2011-05-27 |
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