CZ295522B6 - Substituované aminosloučeniny, způsob jejich výroby a jejich použití jako analgeticky účinných látek - Google Patents
Substituované aminosloučeniny, způsob jejich výroby a jejich použití jako analgeticky účinných látek Download PDFInfo
- Publication number
- CZ295522B6 CZ295522B6 CZ1998755A CZ75598A CZ295522B6 CZ 295522 B6 CZ295522 B6 CZ 295522B6 CZ 1998755 A CZ1998755 A CZ 1998755A CZ 75598 A CZ75598 A CZ 75598A CZ 295522 B6 CZ295522 B6 CZ 295522B6
- Authority
- CZ
- Czechia
- Prior art keywords
- alkyl
- aryl
- formula
- cycloalkyl
- phenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 230000000202 analgesic effect Effects 0.000 title description 5
- 239000013543 active substance Substances 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Chemical group 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 150000003509 tertiary alcohols Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 150000002902 organometallic compounds Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 4
- 229940035676 analgesics Drugs 0.000 abstract description 3
- 239000000730 antalgic agent Substances 0.000 abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- 238000002844 melting Methods 0.000 description 43
- 230000008018 melting Effects 0.000 description 43
- 239000000243 solution Substances 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- -1 amine compounds Chemical class 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 15
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 14
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 238000004440 column chromatography Methods 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 239000003921 oil Substances 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 229960000583 acetic acid Drugs 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 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 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 239000005557 antagonist Substances 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000005051 trimethylchlorosilane Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000008346 aqueous phase Substances 0.000 description 6
- 239000012362 glacial acetic acid Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 230000027455 binding Effects 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 229940127240 opiate Drugs 0.000 description 5
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- 229960005181 morphine Drugs 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- QTVUNSQMUUGNQC-UHFFFAOYSA-N 1-(6-methoxy-1-phenyl-3,4-dihydronaphthalen-2-yl)-n,n-dimethylmethanamine;hydrochloride Chemical compound Cl.CN(C)CC=1CCC2=CC(OC)=CC=C2C=1C1=CC=CC=C1 QTVUNSQMUUGNQC-UHFFFAOYSA-N 0.000 description 3
- PLDWAJLZAAHOGG-UHFFFAOYSA-N 1-bromo-3-methoxybenzene Chemical compound COC1=CC=CC(Br)=C1 PLDWAJLZAAHOGG-UHFFFAOYSA-N 0.000 description 3
- UKECMIDIUBJWFD-UHFFFAOYSA-N 3-[3-(dimethylamino)-1-(3-hydroxyphenyl)-2-methylprop-1-enyl]phenol;hydrochloride Chemical compound Cl.C=1C=CC(O)=CC=1C(=C(C)CN(C)C)C1=CC=CC(O)=C1 UKECMIDIUBJWFD-UHFFFAOYSA-N 0.000 description 3
- ZFOLQUQHELUVNU-UHFFFAOYSA-N 7-phenoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=C2C(=O)CCCC2=CC=C1OC1=CC=CC=C1 ZFOLQUQHELUVNU-UHFFFAOYSA-N 0.000 description 3
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 108700023159 delta Opioid Receptors Proteins 0.000 description 3
- 102000048124 delta Opioid Receptors Human genes 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 229940005483 opioid analgesics Drugs 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 230000002285 radioactive effect Effects 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000010626 work up procedure Methods 0.000 description 3
- ZHUJMSMQIPIPTF-IBURTVSXSA-N (2r)-2-[[(2s)-2-[[2-[[(2r)-2-[[(2s)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]propanoyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoic acid Chemical compound C([C@@H](C(=O)N[C@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)[C@@H](C)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 ZHUJMSMQIPIPTF-IBURTVSXSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- PNIMXRQNKUWAGX-UHFFFAOYSA-N 1-(6-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-N,N-dimethylmethanamine Chemical compound C1C(CN(C)C)CCC2=CC(OC)=CC=C21 PNIMXRQNKUWAGX-UHFFFAOYSA-N 0.000 description 2
- UUJOSTMHTDENMI-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)-3,4-dihydro-2h-naphthalen-1-ol Chemical compound COC1=CC=CC(C2(O)C3=CC=CC=C3CCC2CN(C)C)=C1 UUJOSTMHTDENMI-UHFFFAOYSA-N 0.000 description 2
- OMCOACHXKJOZMD-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=CC=C2C(=O)C(CN(C)C)CCC2=C1 OMCOACHXKJOZMD-UHFFFAOYSA-N 0.000 description 2
- WUYXAUCALCKXHQ-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-6-(3-methoxyphenyl)-3,4-dihydro-2h-naphthalen-1-one Chemical compound COC1=CC=CC(C=2C=C3CCC(CN(C)C)C(=O)C3=CC=2)=C1 WUYXAUCALCKXHQ-UHFFFAOYSA-N 0.000 description 2
- LFBFFWDWORHXGR-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-6-methoxy-1-(3-methoxyphenyl)-3,4-dihydro-2h-naphthalen-1-ol Chemical compound COC1=CC=CC(C2(O)C3=CC=C(OC)C=C3CCC2CN(C)C)=C1 LFBFFWDWORHXGR-UHFFFAOYSA-N 0.000 description 2
- VVEJRVAVPAHKML-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-7-phenoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound C1=C2C(=O)C(CN(C)C)CCC2=CC=C1OC1=CC=CC=C1 VVEJRVAVPAHKML-UHFFFAOYSA-N 0.000 description 2
- BWIJFICFAJDHQZ-UHFFFAOYSA-N 3-(dimethylamino)-1,1-bis(3-methoxyphenyl)-2-methylpropan-1-ol;hydrochloride Chemical compound Cl.COC1=CC=CC(C(O)(C(C)CN(C)C)C=2C=C(OC)C=CC=2)=C1 BWIJFICFAJDHQZ-UHFFFAOYSA-N 0.000 description 2
- HFRHWCBTTZGHBX-UHFFFAOYSA-N 3-[2-[(dimethylamino)methyl]-3,4-dihydronaphthalen-1-yl]phenol;hydrochloride Chemical compound Cl.C12=CC=CC=C2CCC(CN(C)C)=C1C1=CC=CC(O)=C1 HFRHWCBTTZGHBX-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- KWHUHTFXMNQHAA-UHFFFAOYSA-N 6,7,8,9-tetrahydrobenzo[7]annulen-5-one Chemical compound O=C1CCCCC2=CC=CC=C12 KWHUHTFXMNQHAA-UHFFFAOYSA-N 0.000 description 2
- JUVCUDXAEBOYDW-UHFFFAOYSA-N 6-[(dimethylamino)methyl]-5-(3-hydroxyphenyl)-7,8-dihydronaphthalen-2-ol;hydrochloride Chemical compound Cl.C12=CC=C(O)C=C2CCC(CN(C)C)=C1C1=CC=CC(O)=C1 JUVCUDXAEBOYDW-UHFFFAOYSA-N 0.000 description 2
- AVXCMHQNEDKOOG-UHFFFAOYSA-N 6-[(dimethylamino)methyl]-5-phenyl-7,8-dihydronaphthalen-1-ol;hydrochloride Chemical compound Cl.C12=CC=CC(O)=C2CCC(CN(C)C)=C1C1=CC=CC=C1 AVXCMHQNEDKOOG-UHFFFAOYSA-N 0.000 description 2
- RNOFFFXRIYSOOY-UHFFFAOYSA-N 6-[(dimethylamino)methyl]-5-phenyl-7,8-dihydronaphthalen-2-ol;hydrochloride Chemical compound Cl.C12=CC=C(O)C=C2CCC(CN(C)C)=C1C1=CC=CC=C1 RNOFFFXRIYSOOY-UHFFFAOYSA-N 0.000 description 2
- DSXBGEXWACEAQQ-UHFFFAOYSA-N CN(C)CC1C(C2=CC=C(C=C2CC1)OC)(O)C1=CC=CC=C1 Chemical compound CN(C)CC1C(C2=CC=C(C=C2CC1)OC)(O)C1=CC=CC=C1 DSXBGEXWACEAQQ-UHFFFAOYSA-N 0.000 description 2
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
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- 230000003993 interaction Effects 0.000 description 1
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002641 lithium Chemical group 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
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- 108020004084 membrane receptors Proteins 0.000 description 1
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- UZHSEJADLWPNLE-GRGSLBFTSA-N naloxone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(O)C2=C5[C@@]13CCN4CC=C UZHSEJADLWPNLE-GRGSLBFTSA-N 0.000 description 1
- 229960004127 naloxone Drugs 0.000 description 1
- DKJCUVXSBOMWAV-PCWWUVHHSA-N naltrindole Chemical compound N1([C@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CC2=C3[CH]C=CC=C3N=C25)O)CC1)O)CC1CC1 DKJCUVXSBOMWAV-PCWWUVHHSA-N 0.000 description 1
- 239000003887 narcotic antagonist Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 210000002975 pon Anatomy 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
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- 230000002829 reductive effect Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
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- 238000000926 separation method Methods 0.000 description 1
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- 229910002027 silica gel Inorganic materials 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 125000005106 triarylsilyl group Chemical group 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
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- 239000008096 xylene Substances 0.000 description 1
- 108020001612 μ-opioid receptors Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/48—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups
- C07C215/54—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
- C07C211/28—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring having amino groups linked to the six-membered aromatic ring by unsaturated carbon chains
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/64—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/12—One of the condensed rings being a six-membered aromatic ring the other ring being at least seven-membered
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pain & Pain Management (AREA)
- Public Health (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19710628 | 1997-03-14 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CZ75598A3 CZ75598A3 (cs) | 1998-09-16 |
| CZ295522B6 true CZ295522B6 (cs) | 2005-08-17 |
Family
ID=7823396
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ1998755A CZ295522B6 (cs) | 1997-03-14 | 1998-03-12 | Substituované aminosloučeniny, způsob jejich výroby a jejich použití jako analgeticky účinných látek |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US6022895A (https=) |
| EP (1) | EP0864559B1 (https=) |
| JP (1) | JP4132189B2 (https=) |
| KR (1) | KR100579428B1 (https=) |
| CN (1) | CN1243721C (https=) |
| AR (1) | AR010129A1 (https=) |
| AT (1) | ATE218534T1 (https=) |
| AU (1) | AU728501B2 (https=) |
| CA (1) | CA2231975C (https=) |
| CO (1) | CO4940510A1 (https=) |
| CZ (1) | CZ295522B6 (https=) |
| DE (2) | DE19805370A1 (https=) |
| DK (1) | DK0864559T3 (https=) |
| ES (1) | ES2178055T3 (https=) |
| HU (1) | HU226060B1 (https=) |
| IL (1) | IL123647A (https=) |
| MY (1) | MY118828A (https=) |
| NO (1) | NO311128B1 (https=) |
| NZ (1) | NZ329951A (https=) |
| PE (1) | PE59899A1 (https=) |
| PL (1) | PL191727B1 (https=) |
| PT (1) | PT864559E (https=) |
| RU (1) | RU2197474C2 (https=) |
| SI (1) | SI0864559T1 (https=) |
| SK (1) | SK284279B6 (https=) |
| UA (1) | UA56997C2 (https=) |
| UY (1) | UY24919A1 (https=) |
| ZA (1) | ZA982157B (https=) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19830105C1 (de) * | 1998-07-06 | 2000-02-17 | Gruenenthal Gmbh | Acridinderivate |
| DE19963179B4 (de) * | 1999-12-27 | 2009-02-05 | Grünenthal GmbH | Substituierte 1- und 2-Naphthol-Mannichbasen |
| DE10033459A1 (de) * | 2000-07-10 | 2002-01-24 | Gruenenthal Gmbh | Cyclische substituierte Aminomethylverbindungen und diese Verbindungen enthaltende Arzeimittel |
| EA006507B1 (ru) | 2001-10-15 | 2005-12-29 | Янссен Фармацевтика Н.В. | Новые замещенные 4-фенил-4-[1h-имидазол-2-ил] пиперидиновые производные и их применение в качестве селективных непептидных агонистов дельта-опиоидов |
| DE10206403A1 (de) * | 2002-02-14 | 2003-08-28 | Gruenenthal Gmbh | Synthese von Beta-Aminoketonen |
| DE10206405A1 (de) * | 2002-02-14 | 2003-08-28 | Gruenenthal Gmbh | Synthese von substituierten Carbamidestern |
| CL2004000754A1 (es) * | 2003-04-11 | 2005-02-25 | Janssen Pharmaceutica Nv | Uso de compuestos derivados de 4-fenil-4-(1h-imidazol-2-il)piperidina, como agonistas delta-opioides no peptidicos, para preparar un medicamento util en prevenir o tratar trastornos del sistema nervioso central. |
| DE10341534A1 (de) * | 2003-09-09 | 2005-03-31 | Bayer Chemicals Ag | Difluoralkylaromaten |
| AR045939A1 (es) * | 2003-09-25 | 2005-11-16 | Solvay Pharm Bv | Derivados de bencimidazolona y quinazolinona como agonistas de los receptores orl 1 humanos |
| NZ546834A (en) | 2003-10-01 | 2010-03-26 | Adolor Corp | Spirocyclic heterocyclic derivatives and methods of their use |
| DE102004030099A1 (de) * | 2004-06-22 | 2006-01-12 | Grünenthal GmbH | Gesättigte und ungesättigte 3-Pyridyl-benzocycloalkylmethyl-amine als Serotonin- und/oder Noradrenalin-Reuptake-Hemmer und/oder µ-Opioidrezeptor-Modulatoren |
| WO2006023757A2 (en) * | 2004-08-19 | 2006-03-02 | University Of Virginia Patent Foundation | Novel tricyclic, bicyclic, monocyclic, and acyclic amines as potent sodium channel blocking agents |
| US7598261B2 (en) | 2005-03-31 | 2009-10-06 | Adolor Corporation | Spirocyclic heterocyclic derivatives and methods of their use |
| RU2320342C2 (ru) * | 2005-07-27 | 2008-03-27 | ГУ Научно-исследовательский институт кардиологии Томского научного центра Сибирского отделения Российской академии медицинских наук, ГУ НИИ кардиологии ТНЦ СО РАМН | Антиаритмическое средство |
| JP5090639B2 (ja) | 2005-11-18 | 2012-12-05 | 出光興産株式会社 | 芳香族アミン誘導体及びそれを用いた有機エレクトロルミネッセンス素子 |
| US7576207B2 (en) * | 2006-04-06 | 2009-08-18 | Adolor Corporation | Spirocyclic heterocyclic derivatives and methods of their use |
| TWI401237B (zh) * | 2006-07-24 | 2013-07-11 | ３-〔（１ｒ，２ｒ）-３-（二甲基氨基）-１-乙基-２-甲基丙基〕酚之製備 | |
| WO2008033299A2 (en) * | 2006-09-12 | 2008-03-20 | Adolor Corporation | Use of n-containing spirocompounds for the enhancement of cognitive function |
| JP2010519206A (ja) * | 2007-02-16 | 2010-06-03 | シンタ ファーマシューティカルズ コーポレーション | 炎症及び免疫関連使用のための置換縮合環化合物 |
| WO2012100423A1 (en) * | 2011-01-27 | 2012-08-02 | Eli Lilly And Company | Analgesic compounds, methods, and formulations |
| RU2538727C1 (ru) * | 2013-11-15 | 2015-01-10 | Закрытое акционерное общество "Институт экспериментальной фармакологии" | Анальгетическое средство пептидной структуры на основе тридекапептида, содержащего d-октааргининовый вектор |
| CN104844471B (zh) * | 2015-04-21 | 2017-05-03 | 苏州远智医药科技有限公司 | 一种作为dor受体拮抗剂的化合物 |
| CN109896991B (zh) * | 2017-12-08 | 2020-11-20 | 苏州远智医药科技有限公司 | 一种δ阿片受体拮抗剂及其用途和药物组合物 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE623394A (https=) * | ||||
| GB872371A (en) * | 1958-07-07 | 1961-07-05 | Univ Kansas Reseach Foundation | Benzyl amine compounds and means of obtaining the same |
| DE1203247B (de) * | 1961-10-10 | 1965-10-21 | Koninklijke Pharma Fab Nv | Verfahren zur Herstellung von Diphenylalkenyl-aminen sowie deren nicht-toxischen Salzen |
| FR1578702A (https=) * | 1961-10-10 | 1969-08-22 | ||
| DE1149002B (de) * | 1961-10-19 | 1963-05-22 | Giulini Gmbh Geb | Verfahren zur Herstellung von blutdrucksteigernden Salzen von N, N-Dialkyl-2-aethyl-3, 3-diphenyl-propen-(2)-yl-aminen |
| US3452094A (en) * | 1967-07-19 | 1969-06-24 | Geigy Chem Corp | N - 2 - phenyl - 2 - (2 - hydroxy - 1 - naphthyl) ethyl-n-substituted amines and salts thereof |
| RU2005717C1 (ru) * | 1989-02-17 | 1994-01-15 | Такеда кемикал-индастриз Лтд | Способ получения производных аралкиламинов или их кислотно-аддитивных солей |
| DE69333527T2 (de) * | 1993-02-23 | 2005-06-16 | Brigham & Women's Hospital, Inc., Boston | Calciumrezeptoraktive moleküle |
-
1998
- 1998-02-11 DE DE19805370A patent/DE19805370A1/de not_active Withdrawn
- 1998-02-19 PT PT98102853T patent/PT864559E/pt unknown
- 1998-02-19 EP EP98102853A patent/EP0864559B1/de not_active Expired - Lifetime
- 1998-02-19 ES ES98102853T patent/ES2178055T3/es not_active Expired - Lifetime
- 1998-02-19 DE DE59804276T patent/DE59804276D1/de not_active Expired - Lifetime
- 1998-02-19 DK DK98102853T patent/DK0864559T3/da active
- 1998-02-19 AT AT98102853T patent/ATE218534T1/de active
- 1998-02-19 SI SI9830137T patent/SI0864559T1/xx unknown
- 1998-03-09 MY MYPI98001021A patent/MY118828A/en unknown
- 1998-03-09 UY UY24919A patent/UY24919A1/es not_active Application Discontinuation
- 1998-03-11 US US09/038,033 patent/US6022895A/en not_active Expired - Lifetime
- 1998-03-11 AR ARP980101094A patent/AR010129A1/es unknown
- 1998-03-11 CO CO98013443A patent/CO4940510A1/es unknown
- 1998-03-12 UA UA98031284A patent/UA56997C2/uk unknown
- 1998-03-12 CN CNB981078680A patent/CN1243721C/zh not_active Expired - Fee Related
- 1998-03-12 CZ CZ1998755A patent/CZ295522B6/cs not_active IP Right Cessation
- 1998-03-12 IL IL12364798A patent/IL123647A/en not_active IP Right Cessation
- 1998-03-12 CA CA002231975A patent/CA2231975C/en not_active Expired - Fee Related
- 1998-03-12 SK SK333-98A patent/SK284279B6/sk not_active IP Right Cessation
- 1998-03-12 RU RU98105507/04A patent/RU2197474C2/ru active
- 1998-03-12 NZ NZ329951A patent/NZ329951A/en unknown
- 1998-03-12 PE PE1998000170A patent/PE59899A1/es not_active Application Discontinuation
- 1998-03-13 ZA ZA982157A patent/ZA982157B/xx unknown
- 1998-03-13 AU AU58408/98A patent/AU728501B2/en not_active Ceased
- 1998-03-13 NO NO19981121A patent/NO311128B1/no unknown
- 1998-03-13 JP JP06350098A patent/JP4132189B2/ja not_active Expired - Fee Related
- 1998-03-13 HU HU9800555A patent/HU226060B1/hu not_active IP Right Cessation
- 1998-03-13 PL PL325322A patent/PL191727B1/pl not_active IP Right Cessation
- 1998-03-13 KR KR1019980008435A patent/KR100579428B1/ko not_active Expired - Fee Related
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PD00 | Pending as of 2000-06-30 in czech republic | ||
| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20100312 |