ES2304477T3 - Procedimiento de preparacion de compuestos con afinidad a receptores opioides. - Google Patents
Procedimiento de preparacion de compuestos con afinidad a receptores opioides. Download PDFInfo
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- ES2304477T3 ES2304477T3 ES03013544T ES03013544T ES2304477T3 ES 2304477 T3 ES2304477 T3 ES 2304477T3 ES 03013544 T ES03013544 T ES 03013544T ES 03013544 T ES03013544 T ES 03013544T ES 2304477 T3 ES2304477 T3 ES 2304477T3
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 43
- 238000000034 method Methods 0.000 title claims description 21
- 102000003840 Opioid Receptors Human genes 0.000 title claims description 15
- 108090000137 Opioid Receptors Proteins 0.000 title claims description 15
- 238000002360 preparation method Methods 0.000 title claims description 8
- 238000006243 chemical reaction Methods 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 7
- 239000003434 antitussive agent Substances 0.000 claims description 6
- 229940124584 antitussives Drugs 0.000 claims description 6
- 239000001961 anticonvulsive agent Substances 0.000 claims description 5
- 229940035676 analgesics Drugs 0.000 claims description 4
- 239000000730 antalgic agent Substances 0.000 claims description 4
- 229940125681 anticonvulsant agent Drugs 0.000 claims description 4
- 239000003793 antidiarrheal agent Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 238000002483 medication Methods 0.000 claims description 3
- LVVHEFJXPXAUDD-BULFRSBZSA-N 3-[(3r,4r)-1-[(3s)-3-cyclohexyl-3-hydroxypropyl]-3,4-dimethylpiperidin-4-yl]phenol Chemical compound C1([C@@H](O)CCN2C[C@@H]([C@](CC2)(C)C=2C=C(O)C=CC=2)C)CCCCC1 LVVHEFJXPXAUDD-BULFRSBZSA-N 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 14
- 239000003153 chemical reaction reagent Substances 0.000 description 14
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 150000003857 carboxamides Chemical class 0.000 description 12
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 11
- 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 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- -1 hydroxy-amidino Chemical group 0.000 description 10
- YQYVFVRQLZMJKJ-JBBXEZCESA-N (+)-cyclazocine Chemical compound C([C@@]1(C)C2=CC(O)=CC=C2C[C@@H]2[C@@H]1C)CN2CC1CC1 YQYVFVRQLZMJKJ-JBBXEZCESA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
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- 239000000243 solution Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 238000005481 NMR spectroscopy Methods 0.000 description 8
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 206010013663 drug dependence Diseases 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 229960005181 morphine Drugs 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 230000004224 protection Effects 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 4
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 230000004048 modification Effects 0.000 description 4
- 238000012986 modification Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical group FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- SEJUQQOPVAUETF-QHLBDZCJSA-N (2r,6r,11s)-3-(cyclopropylmethyl)-6-ethyl-8-hydroxy-11-methyl-3,4,5,6-tetrahydro-2,6-methano-3-benzazocin-1(2h)-one Chemical compound C([C@@]1([C@@H]([C@@H]2C(=O)C=3C1=CC(O)=CC=3)C)CC)CN2CC1CC1 SEJUQQOPVAUETF-QHLBDZCJSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
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- 102000005962 receptors Human genes 0.000 description 3
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- 238000012360 testing method Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 208000007848 Alcoholism Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101100219382 Caenorhabditis elegans cah-2 gene Proteins 0.000 description 2
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 206010057852 Nicotine dependence Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
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- 238000000262 chemical ionisation mass spectrometry Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
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- 238000010511 deprotection reaction Methods 0.000 description 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
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- 125000000524 functional group Chemical group 0.000 description 2
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- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
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- 239000002243 precursor Substances 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 2
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- 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 1
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- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
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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
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- 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
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/06—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with a hetero atom directly attached in position 14
- C07D489/08—Oxygen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/09—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems
- C07D489/10—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems with a bridge between positions 6 and 14
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/18—Bridged systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
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- Obesity (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
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- Rheumatology (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Vascular Medicine (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24443800P | 2000-10-31 | 2000-10-31 | |
| US244438P | 2000-10-31 | ||
| EP01992702A EP1353909B1 (en) | 2000-10-31 | 2001-10-31 | 8-substituted-2,6-methano-3-benzazocines and 3-substituted morphinanes as opioidreceptor binding agents |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2304477T3 true ES2304477T3 (es) | 2008-10-16 |
Family
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| ES03013544T Expired - Lifetime ES2304477T3 (es) | 2000-10-31 | 2001-10-31 | Procedimiento de preparacion de compuestos con afinidad a receptores opioides. |
| ES08004779T Expired - Lifetime ES2572332T3 (es) | 2000-10-31 | 2001-10-31 | 2,6-metano-3-benzazocinas sustituidas en posición 8 y morfinanos sustituidos en posición 3 como ligandos de receptores opioides |
| ES01992702T Expired - Lifetime ES2239170T3 (es) | 2000-10-31 | 2001-10-31 | 2,6-metano-3-benzazocinas sustituidas en posicion 8 y morfinanos sustituidos en posicion 3 como agentes ligantes a receptores opioides. |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES08004779T Expired - Lifetime ES2572332T3 (es) | 2000-10-31 | 2001-10-31 | 2,6-metano-3-benzazocinas sustituidas en posición 8 y morfinanos sustituidos en posición 3 como ligandos de receptores opioides |
| ES01992702T Expired - Lifetime ES2239170T3 (es) | 2000-10-31 | 2001-10-31 | 2,6-metano-3-benzazocinas sustituidas en posicion 8 y morfinanos sustituidos en posicion 3 como agentes ligantes a receptores opioides. |
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| Country | Link |
|---|---|
| US (9) | US6784187B2 (enExample) |
| EP (3) | EP1353909B1 (enExample) |
| JP (2) | JP4340437B2 (enExample) |
| AT (2) | ATE391712T1 (enExample) |
| AU (2) | AU2002227135B2 (enExample) |
| CA (1) | CA2426942C (enExample) |
| DE (2) | DE60133584T2 (enExample) |
| ES (3) | ES2304477T3 (enExample) |
| WO (1) | WO2002036573A2 (enExample) |
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| DE10141650C1 (de) | 2001-08-24 | 2002-11-28 | Lohmann Therapie Syst Lts | Transdermales Therapeutisches System mit Fentanyl bzw. verwandten Substanzen |
| CN103405431B (zh) * | 2002-05-17 | 2016-04-13 | 台湾J药品有限公司 | 阿片和阿片样化合物及其用途 |
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| US7923454B2 (en) | 2002-05-17 | 2011-04-12 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| CN1758912A (zh) * | 2003-03-07 | 2006-04-12 | 东丽株式会社 | 药物·物质依赖治疗药 |
| US7381721B2 (en) | 2003-03-17 | 2008-06-03 | Adolor Corporation | Substituted piperidine compounds |
| US8017622B2 (en) | 2003-05-16 | 2011-09-13 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US6992090B2 (en) | 2003-06-16 | 2006-01-31 | Adolor Corporation | Substituted piperidine compounds and methods of their use |
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| CA2591963A1 (en) | 2004-12-22 | 2006-06-29 | Janssen Pharmaceutica N.V. | Tricyclic o-opioid modulators |
| EP1833825A1 (en) | 2004-12-22 | 2007-09-19 | Janssen Pharmaceutica N.V. | Tricyclic delta-opioid modulators |
| CA2594347A1 (en) | 2005-01-06 | 2006-07-13 | Janssen Pharmaceutica N.V. | Tricyclic d-opioid modulators |
| WO2006126529A1 (ja) | 2005-05-25 | 2006-11-30 | Shionogi & Co., Ltd. | 6,7-不飽和-7-カルバモイル置換モルヒナン誘導体 |
| CN101243079A (zh) | 2005-06-16 | 2008-08-13 | 詹森药业有限公司 | 三环阿片调节剂 |
| US7557119B2 (en) * | 2005-07-21 | 2009-07-07 | Rensselaer Polytechnic Institute | Large substituent, non-phenolic opioids |
| US7538110B2 (en) | 2005-10-27 | 2009-05-26 | Adolor Corporation | Opioid antagonists |
| TWI425945B (zh) * | 2007-05-28 | 2014-02-11 | Seldar Pharma Inc | 四氫異喹啉-1-酮衍生物或其鹽 |
| CN101827819B (zh) * | 2007-08-09 | 2013-06-12 | 伦斯勒理工学院 | 阿片样物质酰胺季铵盐 |
| ES2534055T3 (es) * | 2008-07-21 | 2015-04-16 | Rensselaer Polytechnic Institute | Opioides de amina no fenólicos con sustituyentes de gran tamaño |
| EP2408303A4 (en) * | 2009-03-19 | 2012-07-25 | Alkermes Inc | MORPHINANE DERIVATIVES HAVING HIGH ORAL BIOLOGICAL AVAILABILITY |
| US8624040B2 (en) | 2009-06-22 | 2014-01-07 | Millennium Pharmaceuticals, Inc. | Substituted hydroxamic acids and uses thereof |
| EP2445340B1 (en) | 2009-06-22 | 2016-05-18 | Millennium Pharmaceuticals, Inc. | Substituted hydroxamic acids and uses thereof |
| US10363251B2 (en) | 2009-07-16 | 2019-07-30 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| MX342548B (es) * | 2009-09-18 | 2016-10-04 | Merck Sharp & Dohme Corp * | Uso del antagonista del receptor opiaceo para los trastornos del tracto gastrointestinal. |
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| CA2793725C (en) | 2010-03-22 | 2018-05-01 | Rensselaer Polytechnic Institute | Carboxamide bioisosteres of opiates |
| US8946223B2 (en) | 2010-04-12 | 2015-02-03 | Millennium Pharmaceuticals, Inc. | Substituted hydroxamic acids and uses thereof |
| US20120010412A1 (en) | 2010-07-08 | 2012-01-12 | Alkermes, Inc. | Process for the Synthesis of Substituted Morphinans |
| ES2728701T3 (es) | 2010-07-16 | 2019-10-28 | Mallinckrodt Llc | (+)-Morfinanos como antagonistas del receptor 9 de tipo Toll y aplicaciones terapéuticas de los mismos |
| PL3446565T3 (pl) | 2010-08-23 | 2024-04-02 | Alkermes Pharma Ireland Limited | Sposoby leczenia przyrostu masy ciała wywołanego lekami przeciwpsychotycznymi |
| US8471026B2 (en) | 2010-08-26 | 2013-06-25 | Millennium Pharmaceuticals, Inc. | Substituted hydroxamic acids and uses thereof |
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| PT2725908T (pt) * | 2011-06-29 | 2017-08-31 | Alkermes Inc | Compostos opioides de ação periférica |
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| CN107873023B (zh) | 2015-02-02 | 2021-07-23 | 福马治疗股份有限公司 | 作为hdac抑制剂的3-烷基-4-酰氨基-双环[4,5,0]异羟肟酸 |
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| US10745402B2 (en) | 2017-01-02 | 2020-08-18 | Purdue Pharma L.P. | Morphinan derivatives and use thereof |
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-
2001
- 2001-10-31 DE DE60133584T patent/DE60133584T2/de not_active Expired - Lifetime
- 2001-10-31 DE DE60109960T patent/DE60109960T2/de not_active Expired - Lifetime
- 2001-10-31 ES ES03013544T patent/ES2304477T3/es not_active Expired - Lifetime
- 2001-10-31 EP EP01992702A patent/EP1353909B1/en not_active Expired - Lifetime
- 2001-10-31 AT AT03013544T patent/ATE391712T1/de not_active IP Right Cessation
- 2001-10-31 EP EP03013544A patent/EP1359146B1/en not_active Expired - Lifetime
- 2001-10-31 EP EP08004779.8A patent/EP1944292B9/en not_active Expired - Lifetime
- 2001-10-31 WO PCT/US2001/045581 patent/WO2002036573A2/en not_active Ceased
- 2001-10-31 JP JP2002539332A patent/JP4340437B2/ja not_active Expired - Lifetime
- 2001-10-31 ES ES08004779T patent/ES2572332T3/es not_active Expired - Lifetime
- 2001-10-31 CA CA2426942A patent/CA2426942C/en not_active Expired - Lifetime
- 2001-10-31 AU AU2002227135A patent/AU2002227135B2/en not_active Expired
- 2001-10-31 ES ES01992702T patent/ES2239170T3/es not_active Expired - Lifetime
- 2001-10-31 AT AT01992702T patent/ATE292625T1/de not_active IP Right Cessation
- 2001-10-31 AU AU2713502A patent/AU2713502A/xx active Pending
-
2002
- 2002-11-26 US US10/305,287 patent/US6784187B2/en not_active Expired - Lifetime
-
2003
- 2003-04-09 US US10/409,803 patent/US6887998B2/en not_active Expired - Lifetime
- 2003-12-19 JP JP2003422779A patent/JP2004137288A/ja active Pending
-
2004
- 2004-11-12 US US10/987,527 patent/US7265226B2/en not_active Expired - Lifetime
-
2005
- 2005-08-17 US US11/205,354 patent/US20060030580A1/en not_active Abandoned
-
2008
- 2008-10-10 US US12/249,238 patent/US7956187B2/en not_active Expired - Fee Related
-
2011
- 2011-05-09 US US13/103,599 patent/US8252929B2/en not_active Expired - Fee Related
-
2012
- 2012-07-24 US US13/556,650 patent/US8642615B2/en not_active Expired - Lifetime
-
2013
- 2013-12-19 US US14/134,264 patent/US20140275545A1/en not_active Abandoned
-
2016
- 2016-09-09 US US15/260,610 patent/US9932349B2/en not_active Expired - Lifetime
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