SK284851B6 - Substituované imidazolidínové deriváty, spôsob ich prípravy, ich použitie a farmaceutické prostriedky, ktoré ich obsahujú - Google Patents
Substituované imidazolidínové deriváty, spôsob ich prípravy, ich použitie a farmaceutické prostriedky, ktoré ich obsahujú Download PDFInfo
- Publication number
- SK284851B6 SK284851B6 SK1580-98A SK158098A SK284851B6 SK 284851 B6 SK284851 B6 SK 284851B6 SK 158098 A SK158098 A SK 158098A SK 284851 B6 SK284851 B6 SK 284851B6
- Authority
- SK
- Slovakia
- Prior art keywords
- group
- carbon atoms
- alkyl
- optionally substituted
- aryl
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 292
- 238000002360 preparation method Methods 0.000 title claims abstract description 43
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
- 150000002462 imidazolines Chemical class 0.000 title abstract 2
- 229940083254 peripheral vasodilators imidazoline derivative Drugs 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 359
- 108010008212 Integrin alpha4beta1 Proteins 0.000 claims abstract description 50
- 238000011321 prophylaxis Methods 0.000 claims abstract description 26
- 238000011282 treatment Methods 0.000 claims abstract description 24
- 239000003814 drug Substances 0.000 claims abstract description 18
- 230000005012 migration Effects 0.000 claims abstract description 13
- 238000013508 migration Methods 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 10
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 8
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract description 7
- 230000007815 allergy Effects 0.000 claims abstract description 5
- 239000003112 inhibitor Substances 0.000 claims abstract description 5
- 229910052721 tungsten Inorganic materials 0.000 claims abstract description 4
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 401
- -1 alkylene radical Chemical class 0.000 claims description 352
- 125000000217 alkyl group Chemical group 0.000 claims description 255
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 154
- 125000003118 aryl group Chemical group 0.000 claims description 146
- 150000003254 radicals Chemical class 0.000 claims description 133
- 239000000203 mixture Substances 0.000 claims description 100
- 150000003839 salts Chemical class 0.000 claims description 71
- 229910052757 nitrogen Inorganic materials 0.000 claims description 58
- 125000003545 alkoxy group Chemical group 0.000 claims description 55
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 46
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 46
- 125000001072 heteroaryl group Chemical group 0.000 claims description 42
- 125000006239 protecting group Chemical group 0.000 claims description 42
- 239000002253 acid Substances 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- 125000003107 substituted aryl group Chemical group 0.000 claims description 37
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 125000003277 amino group Chemical group 0.000 claims description 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 33
- 229910052799 carbon Inorganic materials 0.000 claims description 31
- 125000005842 heteroatom Chemical group 0.000 claims description 30
- 229910052760 oxygen Chemical group 0.000 claims description 30
- 239000001301 oxygen Chemical group 0.000 claims description 30
- 238000009833 condensation Methods 0.000 claims description 29
- 230000005494 condensation Effects 0.000 claims description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
- 150000002148 esters Chemical class 0.000 claims description 28
- 125000001153 fluoro group Chemical group F* 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
- 229910052717 sulfur Inorganic materials 0.000 claims description 25
- 150000001413 amino acids Chemical class 0.000 claims description 24
- 125000000732 arylene group Chemical group 0.000 claims description 24
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 24
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 229920006395 saturated elastomer Polymers 0.000 claims description 24
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 23
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 20
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 18
- 150000001408 amides Chemical class 0.000 claims description 17
- 125000002619 bicyclic group Chemical group 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
- 125000000524 functional group Chemical group 0.000 claims description 16
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 16
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 16
- 239000011593 sulfur Chemical group 0.000 claims description 16
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 229910052731 fluorine Inorganic materials 0.000 claims description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 13
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000005549 heteroarylene group Chemical group 0.000 claims description 12
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 108010016626 Dipeptides Proteins 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 11
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 9
- 208000006673 asthma Diseases 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 9
- 125000004434 sulfur atom Chemical group 0.000 claims description 9
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 8
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 6
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 5
- 150000005840 aryl radicals Chemical class 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000005121 aminocarbonylalkoxy group Chemical group 0.000 claims description 4
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 4
- 239000011737 fluorine Substances 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 4
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 4
- 125000003367 polycyclic group Chemical group 0.000 claims description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 4
- HHAVGBXLGVYXFF-AWEZNQCLSA-N (2r)-n-[3-(heptylamino)-3-oxopropyl]-2,4-dihydroxy-3,3-dimethylbutanamide Chemical compound CCCCCCCNC(=O)CCNC(=O)[C@H](O)C(C)(C)CO HHAVGBXLGVYXFF-AWEZNQCLSA-N 0.000 claims description 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 3
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 3
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 claims description 3
- 125000005418 aryl aryl group Chemical group 0.000 claims description 3
- 229910052796 boron Inorganic materials 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 201000004792 malaria Diseases 0.000 claims description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 210000000056 organ Anatomy 0.000 claims description 3
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 3
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 3
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 206010036030 Polyarthritis Diseases 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 2
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- 208000026278 immune system disease Diseases 0.000 claims description 2
- 229940017219 methyl propionate Drugs 0.000 claims description 2
- 208000030428 polyarticular arthritis Diseases 0.000 claims description 2
- 208000037803 restenosis Diseases 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 2
- 230000004614 tumor growth Effects 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 2
- 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
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- 125000005102 carbonylalkoxy group Chemical group 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 206010061289 metastatic neoplasm Diseases 0.000 claims 1
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 17
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- 239000002464 receptor antagonist Substances 0.000 abstract 1
- 229940044551 receptor antagonist Drugs 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 156
- 229920005989 resin Polymers 0.000 description 78
- 239000011347 resin Substances 0.000 description 78
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 39
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- 210000004027 cell Anatomy 0.000 description 37
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 30
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 23
- XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 22
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- WAKFXKMJYLVGHE-UHFFFAOYSA-N 2,4-dioxoimidazolidine-1-carboxylic acid Chemical compound OC(=O)N1CC(=O)NC1=O WAKFXKMJYLVGHE-UHFFFAOYSA-N 0.000 description 17
- 150000002431 hydrogen Chemical class 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 16
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
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- 201000010099 disease Diseases 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 13
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
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- BFFNZGWJTHWUMY-ZCFIWIBFSA-N tert-butyl (3r)-3-aminobutanoate Chemical compound C[C@@H](N)CC(=O)OC(C)(C)C BFFNZGWJTHWUMY-ZCFIWIBFSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
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- 230000008878 coupling Effects 0.000 description 11
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- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 11
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- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
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- 239000000843 powder Substances 0.000 description 1
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- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- VNUORQWNUXXHLX-UHFFFAOYSA-N pyrazolidine-3-carboxylic acid Chemical compound OC(=O)C1CCNN1 VNUORQWNUXXHLX-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 238000011555 rabbit model Methods 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 230000000979 retarding effect Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
- 230000035483 skin reaction Effects 0.000 description 1
- 231100000430 skin reaction Toxicity 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
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- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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- 125000001174 sulfone group Chemical group 0.000 description 1
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- 239000003765 sweetening agent Substances 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
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- VOBBGGRKFHXGBI-LBPRGKRZSA-N tert-butyl (3s)-3-amino-3-(4-methoxyphenyl)propanoate Chemical compound COC1=CC=C([C@@H](N)CC(=O)OC(C)(C)C)C=C1 VOBBGGRKFHXGBI-LBPRGKRZSA-N 0.000 description 1
- HJLYKRGXTOVWFL-UHFFFAOYSA-N tert-butyl 2-amino-2-phenylacetate Chemical compound CC(C)(C)OC(=O)C(N)C1=CC=CC=C1 HJLYKRGXTOVWFL-UHFFFAOYSA-N 0.000 description 1
- BVRGLGJXQIMHBS-UHFFFAOYSA-N tert-butyl carbonobromidate Chemical compound CC(C)(C)OC(Br)=O BVRGLGJXQIMHBS-UHFFFAOYSA-N 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
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- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
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- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
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- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- DZLNHFMRPBPULJ-UHFFFAOYSA-N thioproline Chemical compound OC(=O)C1CSCN1 DZLNHFMRPBPULJ-UHFFFAOYSA-N 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- PCFIPYFVXDCWBW-UHFFFAOYSA-N tricyclo[3.3.1.03,7]nonane Chemical compound C1C(C2)C3CC2CC1C3 PCFIPYFVXDCWBW-UHFFFAOYSA-N 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000006493 trifluoromethyl benzyl group Chemical group 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
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Classifications
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19751251A DE19751251A1 (de) | 1997-11-19 | 1997-11-19 | Substituierte Imidazolidinderivate, ihre Herstellung, ihre Verwendung und sie enthaltende pharmezeutische Präparate |
Publications (2)
Publication Number | Publication Date |
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SK158098A3 SK158098A3 (en) | 1999-06-11 |
SK284851B6 true SK284851B6 (sk) | 2006-01-05 |
Family
ID=7849203
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Application Number | Title | Priority Date | Filing Date |
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SK1580-98A SK284851B6 (sk) | 1997-11-19 | 1998-11-17 | Substituované imidazolidínové deriváty, spôsob ich prípravy, ich použitie a farmaceutické prostriedky, ktoré ich obsahujú |
Country Status (29)
Country | Link |
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US (2) | US6331552B1 (cs) |
EP (1) | EP0918059B1 (cs) |
JP (1) | JP4567821B2 (cs) |
KR (1) | KR100738820B1 (cs) |
CN (1) | CN1330638C (cs) |
AR (1) | AR016011A1 (cs) |
AT (1) | ATE243708T1 (cs) |
AU (1) | AU755893B2 (cs) |
BR (1) | BR9804695B1 (cs) |
CA (1) | CA2254420C (cs) |
CZ (1) | CZ297564B6 (cs) |
DE (2) | DE19751251A1 (cs) |
DK (1) | DK0918059T3 (cs) |
ES (1) | ES2202718T3 (cs) |
HR (1) | HRP980602B1 (cs) |
HU (1) | HU229481B1 (cs) |
ID (1) | ID21305A (cs) |
IL (1) | IL127132A (cs) |
MY (1) | MY118313A (cs) |
NO (1) | NO325303B1 (cs) |
NZ (1) | NZ332855A (cs) |
PL (1) | PL194692B1 (cs) |
PT (1) | PT918059E (cs) |
RU (1) | RU2239641C2 (cs) |
SI (1) | SI0918059T1 (cs) |
SK (1) | SK284851B6 (cs) |
TR (1) | TR199802344A2 (cs) |
TW (1) | TWI230155B (cs) |
ZA (1) | ZA9810543B (cs) |
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1997
- 1997-11-19 DE DE19751251A patent/DE19751251A1/de not_active Withdrawn
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1998
- 1998-11-13 AT AT98121670T patent/ATE243708T1/de active
- 1998-11-13 DE DE59808804T patent/DE59808804D1/de not_active Expired - Lifetime
- 1998-11-13 SI SI9830509T patent/SI0918059T1/xx unknown
- 1998-11-13 DK DK98121670T patent/DK0918059T3/da active
- 1998-11-13 ES ES98121670T patent/ES2202718T3/es not_active Expired - Lifetime
- 1998-11-13 PT PT98121670T patent/PT918059E/pt unknown
- 1998-11-13 EP EP98121670A patent/EP0918059B1/de not_active Expired - Lifetime
- 1998-11-16 ID IDP981494A patent/ID21305A/id unknown
- 1998-11-17 NZ NZ332855A patent/NZ332855A/en not_active IP Right Cessation
- 1998-11-17 HU HU9802653A patent/HU229481B1/hu not_active IP Right Cessation
- 1998-11-17 CZ CZ0372698A patent/CZ297564B6/cs not_active IP Right Cessation
- 1998-11-17 TR TR1998/02344A patent/TR199802344A2/xx unknown
- 1998-11-17 AR ARP980105821A patent/AR016011A1/es active IP Right Grant
- 1998-11-17 SK SK1580-98A patent/SK284851B6/sk not_active IP Right Cessation
- 1998-11-17 CA CA002254420A patent/CA2254420C/en not_active Expired - Fee Related
- 1998-11-18 JP JP32850298A patent/JP4567821B2/ja not_active Expired - Fee Related
- 1998-11-18 AU AU92421/98A patent/AU755893B2/en not_active Ceased
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- 1998-11-18 BR BRPI9804695-0A patent/BR9804695B1/pt not_active IP Right Cessation
- 1998-11-18 RU RU98120859/04A patent/RU2239641C2/ru not_active IP Right Cessation
- 1998-11-18 NO NO19985368A patent/NO325303B1/no not_active IP Right Cessation
- 1998-11-18 ZA ZA9810543A patent/ZA9810543B/xx unknown
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Legal Events
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MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20151117 |