BG60407B2 - Нови фармакологичноактивни съединения, методи за тяхното получаване и състави, съдържащи тези съединения - Google Patents
Нови фармакологичноактивни съединения, методи за тяхното получаване и състави, съдържащи тези съединения Download PDFInfo
- Publication number
- BG60407B2 BG60407B2 BG098383A BG9838394A BG60407B2 BG 60407 B2 BG60407 B2 BG 60407B2 BG 098383 A BG098383 A BG 098383A BG 9838394 A BG9838394 A BG 9838394A BG 60407 B2 BG60407 B2 BG 60407B2
- Authority
- BG
- Bulgaria
- Prior art keywords
- dihydroxy
- nitrophenyl
- formula
- compound
- acid
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 67
- 238000000034 method Methods 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 239000000203 mixture Substances 0.000 title claims description 30
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 6
- 208000020401 Depressive disease Diseases 0.000 claims abstract description 4
- 206010019280 Heart failures Diseases 0.000 claims abstract description 4
- 206010020772 Hypertension Diseases 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract 2
- 239000000243 solution Substances 0.000 claims description 52
- -1 4-quinolyl Chemical group 0.000 claims description 23
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 23
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 23
- 229960004502 levodopa Drugs 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000003435 aroyl group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 4
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 3
- KZGBADQGBKGUGS-FPYGCLRLSA-N ethyl (e)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)prop-2-enoate Chemical compound CCOC(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 KZGBADQGBKGUGS-FPYGCLRLSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000005936 piperidyl group Chemical group 0.000 claims description 3
- UTCONHFSIFTRPV-HMMKTVFPSA-N (2e,5e)-2,5-bis[(3,4-dihydroxy-5-nitrophenyl)methylidene]cyclopentan-1-one Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(\C=C/2C(C(=C/C=3C=C(C(O)=C(O)C=3)[N+]([O-])=O)/CC\2)=O)=C1 UTCONHFSIFTRPV-HMMKTVFPSA-N 0.000 claims description 2
- YTGLKZTVRNTRFM-UHFFFAOYSA-N 1-(3,4-dihydroxy-5-nitrophenyl)-3-[4-(dimethylamino)phenyl]prop-2-en-1-one Chemical compound C1=CC(N(C)C)=CC=C1C=CC(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 YTGLKZTVRNTRFM-UHFFFAOYSA-N 0.000 claims description 2
- VNTWJPNLLBXHIY-UHFFFAOYSA-N 1-(4-benzylpiperazin-1-yl)-5-(3,4-dihydroxy-5-nitrophenyl)pentan-1-one;hydrochloride Chemical compound Cl.[O-][N+](=O)C1=C(O)C(O)=CC(CCCCC(=O)N2CCN(CC=3C=CC=CC=3)CC2)=C1 VNTWJPNLLBXHIY-UHFFFAOYSA-N 0.000 claims description 2
- XHPDHXXZBWDFIB-UHFFFAOYSA-N 2,3-dihydroxybenzonitrile Chemical compound OC1=CC=CC(C#N)=C1O XHPDHXXZBWDFIB-UHFFFAOYSA-N 0.000 claims description 2
- BVNUFRQBMSNFBH-UHFFFAOYSA-N 2-[3-(3,4-dihydroxy-5-nitrophenyl)prop-2-enoyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 BVNUFRQBMSNFBH-UHFFFAOYSA-N 0.000 claims description 2
- JRURYQJSLYLRLN-UHFFFAOYSA-N 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide Chemical compound CCN(CC)C(=O)C(C#N)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-UHFFFAOYSA-N 0.000 claims description 2
- NGYPAALNWRGOQF-UHFFFAOYSA-N 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-n-(3-hydroxypropyl)prop-2-enamide Chemical compound OCCCNC(=O)C(C#N)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 NGYPAALNWRGOQF-UHFFFAOYSA-N 0.000 claims description 2
- NUDNKWSJIXVGSR-UHFFFAOYSA-N 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-n-propan-2-ylprop-2-enamide Chemical compound CC(C)NC(=O)C(C#N)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 NUDNKWSJIXVGSR-UHFFFAOYSA-N 0.000 claims description 2
- WMVQYGLKWBXMMT-UHFFFAOYSA-N 3-(3,4-dihydroxy-5-nitrophenyl)-1-(2-hydroxyphenyl)prop-2-en-1-one Chemical compound OC1=CC=CC=C1C(=O)C=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 WMVQYGLKWBXMMT-UHFFFAOYSA-N 0.000 claims description 2
- DRUCSFHPUMZHFZ-UHFFFAOYSA-N 3-(3,4-dihydroxy-5-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one Chemical compound COC1=C(OC)C(OC)=CC(C(=O)C=CC=2C=C(C(O)=C(O)C=2)[N+]([O-])=O)=C1 DRUCSFHPUMZHFZ-UHFFFAOYSA-N 0.000 claims description 2
- GQBUCKFJGCPIAT-UHFFFAOYSA-N 3-(3,4-dihydroxy-5-nitrophenyl)-1-(3,4-dimethoxyphenyl)prop-2-en-1-one Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)C=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 GQBUCKFJGCPIAT-UHFFFAOYSA-N 0.000 claims description 2
- XFNCZWUJTMVCCW-UHFFFAOYSA-N 3-(3,4-dihydroxy-5-nitrophenyl)-1-(4-methoxyphenyl)prop-2-en-1-one Chemical compound C1=CC(OC)=CC=C1C(=O)C=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 XFNCZWUJTMVCCW-UHFFFAOYSA-N 0.000 claims description 2
- KEEJYRVPFGKFOM-UHFFFAOYSA-N 3-(3,4-dihydroxy-5-nitrophenyl)-1-(4-methylphenyl)prop-2-en-1-one Chemical compound C1=CC(C)=CC=C1C(=O)C=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 KEEJYRVPFGKFOM-UHFFFAOYSA-N 0.000 claims description 2
- LBDCLHWQPHVBTC-UHFFFAOYSA-N 3-(3,4-dihydroxy-5-nitrophenyl)-1-(4-nitrophenyl)prop-2-en-1-one Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C=CC(=O)C=2C=CC(=CC=2)[N+]([O-])=O)=C1 LBDCLHWQPHVBTC-UHFFFAOYSA-N 0.000 claims description 2
- GOWRJXXUELPHCD-UHFFFAOYSA-N 3-(3,4-dihydroxy-5-nitrophenyl)-1-phenylprop-2-en-1-one Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C=CC(=O)C=2C=CC=CC=2)=C1 GOWRJXXUELPHCD-UHFFFAOYSA-N 0.000 claims description 2
- JSTMJRRWBOVARV-UHFFFAOYSA-N 3-nitro-5-(1h-pyrrol-2-ylmethyl)benzene-1,2-diol Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(CC=2NC=CC=2)=C1 JSTMJRRWBOVARV-UHFFFAOYSA-N 0.000 claims description 2
- MQOJOPBNUNCZGI-UHFFFAOYSA-N 3-nitro-5-(2-pyridin-4-ylethenyl)benzene-1,2-diol Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C=CC=2C=CN=CC=2)=C1 MQOJOPBNUNCZGI-UHFFFAOYSA-N 0.000 claims description 2
- NMLXKCGWGRMMJM-UHFFFAOYSA-N 5-(3,4-dihydroxy-5-nitrophenyl)-n-propan-2-ylpentanamide Chemical compound CC(C)NC(=O)CCCCC1=CC(O)=C(O)C([N+]([O-])=O)=C1 NMLXKCGWGRMMJM-UHFFFAOYSA-N 0.000 claims description 2
- WWDJBWMMHXMHND-UHFFFAOYSA-N 5-(3-hydroxy-2-methylbut-1-enyl)-3-nitrobenzene-1,2-diol Chemical compound CC(O)C(C)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 WWDJBWMMHXMHND-UHFFFAOYSA-N 0.000 claims description 2
- GXHFTPOHUPPXDP-UHFFFAOYSA-N 5-[3-[3-(3,4-dihydroxy-5-nitrophenyl)-2-methoxypropoxy]-2-methoxypropyl]-3-nitrobenzene-1,2-diol Chemical compound C=1C(O)=C(O)C([N+]([O-])=O)=CC=1CC(OC)COCC(OC)CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 GXHFTPOHUPPXDP-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- UPMRZALMHVUCIN-UHFFFAOYSA-N Nitecapone Chemical compound CC(=O)C(C(C)=O)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 UPMRZALMHVUCIN-UHFFFAOYSA-N 0.000 claims description 2
- FGMBOCPPYYFLJB-UHFFFAOYSA-N [2-acetyloxy-3-nitro-5-(3-oxo-3-phenylprop-1-enyl)phenyl] acetate Chemical compound [O-][N+](=O)C1=C(OC(C)=O)C(OC(=O)C)=CC(C=CC(=O)C=2C=CC=CC=2)=C1 FGMBOCPPYYFLJB-UHFFFAOYSA-N 0.000 claims description 2
- FGDKGGWWCARTIR-UHFFFAOYSA-N [2-acetyloxy-5-(1-adamantylcarbamoyl)-3-cyanophenyl] acetate Chemical compound N#CC1=C(OC(C)=O)C(OC(=O)C)=CC(C(=O)NC23CC4CC(CC(C4)C2)C3)=C1 FGDKGGWWCARTIR-UHFFFAOYSA-N 0.000 claims description 2
- UIRWYZJMXSYMTD-UHFFFAOYSA-N [2-acetyloxy-5-(1-adamantylcarbamoyl)-3-nitrophenyl] acetate Chemical compound [O-][N+](=O)C1=C(OC(C)=O)C(OC(=O)C)=CC(C(=O)NC23CC4CC(CC(C4)C2)C3)=C1 UIRWYZJMXSYMTD-UHFFFAOYSA-N 0.000 claims description 2
- NTZOGOQNAIGGFG-UHFFFAOYSA-N [2-acetyloxy-5-[4-(cyclohexanecarbonyl)piperidine-1-carbonyl]-3-nitrophenyl] acetate Chemical compound [O-][N+](=O)C1=C(OC(C)=O)C(OC(=O)C)=CC(C(=O)N2CCC(CC2)C(=O)C2CCCCC2)=C1 NTZOGOQNAIGGFG-UHFFFAOYSA-N 0.000 claims description 2
- QNPGHROFDQAAIB-UHFFFAOYSA-N [5-(2-acetyl-3-oxobut-1-enyl)-2-hydroxy-3-nitrophenyl] 2,2-dimethylpropanoate Chemical compound CC(=O)C(C(C)=O)=CC1=CC(OC(=O)C(C)(C)C)=C(O)C([N+]([O-])=O)=C1 QNPGHROFDQAAIB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000005019 carboxyalkenyl group Chemical group 0.000 claims description 2
- BSSKJZZQJGXADF-UHFFFAOYSA-N cyclohexyl-[1-(3,4-dihydroxy-5-nitrobenzoyl)piperidin-4-yl]methanone Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C(=O)N2CCC(CC2)C(=O)C2CCCCC2)=C1 BSSKJZZQJGXADF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- PLQOHSJGIYXROC-UHFFFAOYSA-N ethyl 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)propanoate Chemical compound CCOC(=O)C(C#N)CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 PLQOHSJGIYXROC-UHFFFAOYSA-N 0.000 claims description 2
- 239000004312 hexamethylene tetramine Substances 0.000 claims description 2
- 235000010299 hexamethylene tetramine Nutrition 0.000 claims description 2
- 150000002576 ketones Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- YUYXUNQTIKONFA-UHFFFAOYSA-N methyl 3-[(3,4-dihydroxy-5-nitrophenyl)methylidene]-4-oxopentanoate Chemical compound COC(=O)CC(C(C)=O)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 YUYXUNQTIKONFA-UHFFFAOYSA-N 0.000 claims description 2
- IALCRFZLEQENBW-UHFFFAOYSA-N n-(1-adamantyl)-3,4-dihydroxy-5-nitrobenzamide Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C(=O)NC23CC4CC(CC(C4)C2)C3)=C1 IALCRFZLEQENBW-UHFFFAOYSA-N 0.000 claims description 2
- CCRNCWDQAOTBHN-UHFFFAOYSA-N n-benzyl-3,4-dihydroxy-5-nitrobenzamide Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(C(=O)NCC=2C=CC=CC=2)=C1 CCRNCWDQAOTBHN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 239000003954 decarboxylase inhibitor Substances 0.000 claims 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 3
- SBPVYFCVGGEBHS-UHFFFAOYSA-N 2-[(3,4-dihydroxy-5-nitrophenyl)methyl]-3-hydroxypropanenitrile Chemical compound OCC(C#N)CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 SBPVYFCVGGEBHS-UHFFFAOYSA-N 0.000 claims 1
- RBGDLYUEXLWQBZ-UHFFFAOYSA-N 2-chlorobenzamide Chemical compound NC(=O)C1=CC=CC=C1Cl RBGDLYUEXLWQBZ-UHFFFAOYSA-N 0.000 claims 1
- IZXCSWDOAKESAA-UHFFFAOYSA-N 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)prop-2-enamide Chemical compound NC(=O)C(C#N)=CC1=CC(O)=C(O)C([N+]([O-])=O)=C1 IZXCSWDOAKESAA-UHFFFAOYSA-N 0.000 claims 1
- JXPDNDHCMMOJPC-UHFFFAOYSA-N 2-hydroxybutanedinitrile Chemical compound N#CC(O)CC#N JXPDNDHCMMOJPC-UHFFFAOYSA-N 0.000 claims 1
- VPCLKKWUDVSKID-UHFFFAOYSA-N 3-(3,4-dihydroxy-5-nitrophenyl)propanethioic s-acid Chemical compound OC(=S)CCC1=CC(O)=C(O)C([N+]([O-])=O)=C1 VPCLKKWUDVSKID-UHFFFAOYSA-N 0.000 claims 1
- SNQFMNUMODTUJX-UHFFFAOYSA-N 5-(3,4-dihydroxy-5-nitrophenyl)-n-methyl-n-prop-2-ynylpentanamide Chemical compound C#CCN(C)C(=O)CCCCC1=CC(O)=C(O)C([N+]([O-])=O)=C1 SNQFMNUMODTUJX-UHFFFAOYSA-N 0.000 claims 1
- CZEJERLLAYSVQJ-UHFFFAOYSA-N [2-acetyloxy-5-(1-adamantylcarbamoyl)-3-chlorophenyl] acetate Chemical compound ClC1=C(OC(C)=O)C(OC(=O)C)=CC(C(=O)NC23CC4CC(CC(C4)C2)C3)=C1 CZEJERLLAYSVQJ-UHFFFAOYSA-N 0.000 claims 1
- UHPUZYLXKFZVFP-UHFFFAOYSA-N [2-acetyloxy-5-(benzylcarbamoyl)-3-nitrophenyl] acetate Chemical compound [O-][N+](=O)C1=C(OC(C)=O)C(OC(=O)C)=CC(C(=O)NCC=2C=CC=CC=2)=C1 UHPUZYLXKFZVFP-UHFFFAOYSA-N 0.000 claims 1
- 239000003377 acid catalyst Substances 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims 1
- 239000002775 capsule Substances 0.000 claims 1
- 230000035622 drinking Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- RLPFJGCLLIGOMQ-UHFFFAOYSA-N n-(1-adamantyl)-3-cyano-4,5-dihydroxybenzamide Chemical compound N#CC1=C(O)C(O)=CC(C(=O)NC23CC4CC(CC(C4)C2)C3)=C1 RLPFJGCLLIGOMQ-UHFFFAOYSA-N 0.000 claims 1
- OENSXLFBMLMJOF-UHFFFAOYSA-N n-(1-adamantyl)-5-(3,4-dihydroxy-5-nitrophenyl)pentanamide Chemical compound [O-][N+](=O)C1=C(O)C(O)=CC(CCCCC(=O)NC23CC4CC(CC(C4)C2)C3)=C1 OENSXLFBMLMJOF-UHFFFAOYSA-N 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 239000003826 tablet Substances 0.000 claims 1
- PJZQPGWMGLBVEA-UHFFFAOYSA-N tetradecyl 5-(3,4-diacetyloxy-5-nitrophenyl)pentanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCC1=CC(OC(C)=O)=C(OC(C)=O)C([N+]([O-])=O)=C1 PJZQPGWMGLBVEA-UHFFFAOYSA-N 0.000 claims 1
- QZJHVSWEEUPIEC-UHFFFAOYSA-N tetradecyl 5-(3,4-dihydroxy-5-nitrophenyl)pentanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCC1=CC(O)=C(O)C([N+]([O-])=O)=C1 QZJHVSWEEUPIEC-UHFFFAOYSA-N 0.000 claims 1
- DQSYJYHCGLDHAT-UHFFFAOYSA-N tetradecyl 5-[3-(2,2-dimethylpropanoyloxy)-4-hydroxy-5-nitrophenyl]pentanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCC1=CC(OC(=O)C(C)(C)C)=C(O)C([N+]([O-])=O)=C1 DQSYJYHCGLDHAT-UHFFFAOYSA-N 0.000 claims 1
- 239000000047 product Substances 0.000 description 48
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- BBFJODMCHICIAA-UHFFFAOYSA-N 3,4-dihydroxy-5-nitrobenzaldehyde Chemical compound OC1=CC(C=O)=CC([N+]([O-])=O)=C1O BBFJODMCHICIAA-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 20
- 239000003543 catechol methyltransferase inhibitor Substances 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
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- AOSWUCNPBAIISM-UHFFFAOYSA-N 5-[3-(2,2-dimethylpropanoyloxy)-4-hydroxy-5-nitrophenyl]pentanoic acid Chemical compound CC(C)(C)C(=O)OC1=CC(CCCCC(O)=O)=CC([N+]([O-])=O)=C1O AOSWUCNPBAIISM-UHFFFAOYSA-N 0.000 description 1
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- UBAVSEMCOMZATK-UHFFFAOYSA-N [2-hydroxy-3-nitro-5-(3-oxo-3-phenylprop-1-enyl)phenyl] 2,2-dimethylpropanoate Chemical compound [O-][N+](=O)C1=C(O)C(OC(=O)C(C)(C)C)=CC(C=CC(=O)C=2C=CC=CC=2)=C1 UBAVSEMCOMZATK-UHFFFAOYSA-N 0.000 description 1
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- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 125000003438 dodecyl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- YSKILQPVKFEWDD-UHFFFAOYSA-N ethyl 2-[[2-hydroxy-3-nitro-5-(3-oxo-3-phenylprop-1-enyl)phenoxy]carbonylamino]acetate Chemical compound [O-][N+](=O)C1=C(O)C(OC(=O)NCC(=O)OCC)=CC(C=CC(=O)C=2C=CC=CC=2)=C1 YSKILQPVKFEWDD-UHFFFAOYSA-N 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
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- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
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- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
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- 125000002757 morpholinyl group Chemical group 0.000 description 1
- RPUFERHPLAVBJN-UHFFFAOYSA-N n,n-dihydroxy-1-phenylmethanamine Chemical compound ON(O)CC1=CC=CC=C1 RPUFERHPLAVBJN-UHFFFAOYSA-N 0.000 description 1
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 1
- YLRRYFLYJYRKJG-UHFFFAOYSA-N n-(1-adamantyl)-3-chloro-4,5-dihydroxybenzamide Chemical compound ClC1=C(O)C(O)=CC(C(=O)NC23CC4CC(CC(C4)C2)C3)=C1 YLRRYFLYJYRKJG-UHFFFAOYSA-N 0.000 description 1
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- PGKVPHVPNDBJTO-UHFFFAOYSA-N nitroapocynin Chemical compound COC1=CC(C(C)=O)=CC([N+]([O-])=O)=C1O PGKVPHVPNDBJTO-UHFFFAOYSA-N 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- WTBAHSZERDXKKZ-UHFFFAOYSA-N octadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCCCC(Cl)=O WTBAHSZERDXKKZ-UHFFFAOYSA-N 0.000 description 1
- WLGDAKIJYPIYLR-UHFFFAOYSA-N octane-1-sulfonic acid Chemical compound CCCCCCCCS(O)(=O)=O WLGDAKIJYPIYLR-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940100692 oral suspension Drugs 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 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
- 150000003573 thiols Chemical class 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
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- 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
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/20—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings
- C07C205/21—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings having nitro groups and hydroxy groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C205/22—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings having nitro groups and hydroxy groups bound to carbon atoms of the same non-condensed six-membered aromatic ring having one nitro groups bound to the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/20—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings
- C07C205/21—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings having nitro groups and hydroxy groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C205/23—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings having nitro groups and hydroxy groups bound to carbon atoms of the same non-condensed six-membered aromatic ring having two nitro groups bound to the ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/26—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups and being further substituted by halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
- C07C205/34—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups bound to carbon atoms of six-membered aromatic rings and etherified hydroxy groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
- C07C205/35—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/36—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
- C07C205/37—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/39—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups
- C07C205/42—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/43—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by esterified hydroxy groups having nitro groups or esterified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton to carbon atoms of the same non-condensed six-membered aromatic ring or to carbon atoms of six-membered aromatic rings being part of the same condensed ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/45—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by at least one doubly—bound oxygen atom, not being part of a —CHO group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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FI864875A FI864875A0 (fi) | 1986-11-28 | 1986-11-28 | Nya farmakologiskt aktiva foereningar, dessa innehaollande kompositioner samt foerfarande och mellanprodukter foer anvaendning vid framstaellning av dessa. |
GB878712437A GB8712437D0 (en) | 1986-11-28 | 1987-05-27 | Pharmacologically active compounds |
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BG60407B2 true BG60407B2 (bg) | 1995-02-28 |
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BG098383A BG60407B2 (bg) | 1986-11-28 | 1994-01-18 | Нови фармакологичноактивни съединения, методи за тяхното получаване и състави, съдържащи тези съединения |
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US (1) | US4963590A (fr) |
JP (2) | JPH085781B2 (fr) |
CN (1) | CN1040062C (fr) |
AR (1) | AR243491A1 (fr) |
AT (1) | AT401053B (fr) |
AU (1) | AU621036B2 (fr) |
BE (1) | BE1003279A5 (fr) |
BG (1) | BG60407B2 (fr) |
CA (2) | CA1289078C (fr) |
CH (1) | CH685436A5 (fr) |
CS (4) | CS277018B6 (fr) |
DE (2) | DE19975025I2 (fr) |
DK (1) | DK175394B1 (fr) |
EG (1) | EG18338A (fr) |
ES (1) | ES2008359A6 (fr) |
FR (1) | FR2607493B1 (fr) |
GB (1) | GB2200109B (fr) |
GR (1) | GR871817B (fr) |
HK (1) | HK75594A (fr) |
HU (1) | HU206073B (fr) |
IE (1) | IE60320B1 (fr) |
IS (1) | IS1753B (fr) |
IT (1) | IT1225762B (fr) |
LU (1) | LU87050A1 (fr) |
LV (1) | LV10236B (fr) |
MA (1) | MA21120A1 (fr) |
MT (1) | MTP1012B (fr) |
NL (2) | NL194821C (fr) |
NO (1) | NO171450C (fr) |
NZ (1) | NZ222729A (fr) |
PH (1) | PH26145A (fr) |
PL (1) | PL152642B1 (fr) |
PT (1) | PT86236B (fr) |
RU (1) | RU2014319C1 (fr) |
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YU (3) | YU213587A (fr) |
Families Citing this family (138)
Publication number | Priority date | Publication date | Assignee | Title |
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US5236952A (en) * | 1986-03-11 | 1993-08-17 | Hoffmann-La Roche Inc. | Catechol derivatives |
US5283352A (en) * | 1986-11-28 | 1994-02-01 | Orion-Yhtyma Oy | Pharmacologically active compounds, methods for the preparation thereof and compositions containing the same |
GB9004348D0 (en) * | 1990-02-27 | 1990-04-25 | Orion Yhtymae Oy | New use of catechol derivatives and their physiologically acceptable salts and esters |
MTP1031B (en) * | 1987-12-24 | 1990-10-04 | Orion Yhtymae Oy | New use of cathecol-o-methyl transferase (comt) inhibitors and their physiologically acceptable salts and esters |
AU632992B2 (en) * | 1987-12-24 | 1993-01-21 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Pharmaceutical compositions comprising benzylidene- and cinnamylidene-malononitrile derivatives for the inhibition of proliferative processes in mammalian cells, certain such novel compounds and their preparation |
US5232923A (en) * | 1988-03-18 | 1993-08-03 | Mitsui Toatsu Chemicals, Incorporated | Catechol derivatives and pharmaceutical preparations containing same |
AU618595B2 (en) * | 1988-04-28 | 1992-01-02 | Suntory Limited | Derivative of caffeic acid and pharmaceutical composition containing the same |
US5185370A (en) * | 1988-09-01 | 1993-02-09 | Orion-Yhtyma Oy | Substituted β-diketones and their use |
GB9002337D0 (en) * | 1990-02-02 | 1990-04-04 | Orion Yhtymae Oy | Compounds useful in treating inflammatory bowel disease |
IL91382A (en) * | 1988-09-01 | 1995-06-29 | Orion Yhtymae Oy | Dicitons are converted into alkanyl or ethylmethylene, through their preparation and pharmaceutical preparations containing them |
JPH085780B2 (ja) * | 1989-04-28 | 1996-01-24 | 呉羽化学工業株式会社 | 変形性関節症治療剤 |
GB2238047B (en) * | 1989-11-03 | 1993-02-10 | Orion Yhtymae Oy | Stable polymorphic form of (e)-n,n-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide and the process for its preparation |
GB9113431D0 (en) * | 1991-06-20 | 1991-08-07 | Orion Yhytma Oy | Method for the preparation of 3,4-dihydroxy-5-nitrobenzaldehyde |
JPH05301838A (ja) * | 1991-10-15 | 1993-11-16 | Mitsubishi Kasei Corp | スチレン誘導体 |
PT650476E (pt) * | 1993-04-07 | 2002-11-29 | Otsuka Pharma Co Ltd | Agente vasodilatador periferico que contem derivados n-acilados de 4-amino-piperidina como ingredientes activos |
GB9419274D0 (en) * | 1994-09-23 | 1994-11-09 | Orion Yhtymae Oy | New method for the preparation of 3,4-dihydroxy-5-nitrobenzaldehyde |
GB9510481D0 (en) * | 1995-05-24 | 1995-07-19 | Orion Yhtymae Oy | New catechol derivatives |
GB2316944B (en) * | 1995-05-24 | 1999-01-20 | Orion Yhtymae Oy | New catechol derivatives |
GB9626472D0 (en) | 1996-12-20 | 1997-02-05 | Aperia Anita C | New use of comt inhibitors |
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- 1987-11-27 DK DK198706230A patent/DK175394B1/da not_active IP Right Cessation
- 1987-11-27 NZ NZ222729A patent/NZ222729A/en unknown
- 1987-11-27 LU LU87050A patent/LU87050A1/fr unknown
- 1987-11-27 NL NL8702857A patent/NL194821C/nl not_active IP Right Cessation
- 1987-11-30 IE IE324287A patent/IE60320B1/en not_active IP Right Cessation
-
1988
- 1988-12-19 CS CS888439A patent/CS843988A3/cs unknown
- 1988-12-19 CS CS888440A patent/CS844088A3/cs unknown
-
1989
- 1989-01-06 YU YU2289A patent/YU47790B/sh unknown
- 1989-01-06 YU YU2189A patent/YU48020B/sh unknown
-
1993
- 1993-06-30 LV LVP-93-805A patent/LV10236B/en unknown
-
1994
- 1994-01-18 BG BG098383A patent/BG60407B2/bg unknown
- 1994-08-04 HK HK75594A patent/HK75594A/xx not_active IP Right Cessation
-
2003
- 2003-09-26 NL NL300136C patent/NL300136I2/nl unknown
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