DE3717291A1 - Imidazochinolinyletherderivate, verfahren zu deren herstellung und diese verbindungen enthaltende pharmazeutische mittel - Google Patents
Imidazochinolinyletherderivate, verfahren zu deren herstellung und diese verbindungen enthaltende pharmazeutische mittelInfo
- Publication number
- DE3717291A1 DE3717291A1 DE19873717291 DE3717291A DE3717291A1 DE 3717291 A1 DE3717291 A1 DE 3717291A1 DE 19873717291 DE19873717291 DE 19873717291 DE 3717291 A DE3717291 A DE 3717291A DE 3717291 A1 DE3717291 A1 DE 3717291A1
- Authority
- DE
- Germany
- Prior art keywords
- imidazo
- dihydro
- quinolin
- oxo
- oxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 title claims description 147
- 238000000034 method Methods 0.000 title claims description 63
- 238000004519 manufacturing process Methods 0.000 title description 6
- 239000008177 pharmaceutical agent Substances 0.000 title description 2
- MOJBIJPADSWXCM-UHFFFAOYSA-N 2-(3h-imidazo[4,5-h]quinolin-2-yloxy)-3h-imidazo[4,5-h]quinoline Chemical class C1=CC=NC2=C(NC(OC=3NC4=C5N=CC=CC5=CC=C4N=3)=N3)C3=CC=C21 MOJBIJPADSWXCM-UHFFFAOYSA-N 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims description 243
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 71
- -1 4-phenylpiperazinyl group Chemical group 0.000 claims description 51
- 239000002253 acid Substances 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 125000004432 carbon atom Chemical group C* 0.000 claims description 34
- 229910052740 iodine Inorganic materials 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- 150000002148 esters Chemical class 0.000 claims description 19
- 229940091173 hydantoin Drugs 0.000 claims description 16
- XNHZEJRZFBXTOB-UHFFFAOYSA-N 4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoic acid Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)O)=CC=C21 XNHZEJRZFBXTOB-UHFFFAOYSA-N 0.000 claims description 15
- 125000004043 oxo group Chemical group O=* 0.000 claims description 15
- 241000282414 Homo sapiens Species 0.000 claims description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 13
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 12
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 11
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 11
- 150000001408 amides Chemical class 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 241001465754 Metazoa Species 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 150000001469 hydantoins Chemical class 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 150000003254 radicals Chemical group 0.000 claims description 7
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical group CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 150000002576 ketones Chemical class 0.000 claims description 6
- WORHBDQKZCWBBV-UHFFFAOYSA-N 4-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]butanoic acid Chemical compound OC(=O)CCCOC1=CC=C2N=C(NC(N3C)=O)C3=CC2=C1 WORHBDQKZCWBBV-UHFFFAOYSA-N 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 230000000297 inotrophic effect Effects 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- VUHFMTBOSKAVGD-UHFFFAOYSA-N 5-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]pentanoic acid Chemical compound OC(=O)CCCCOC1=CC=C2N=C(NC(N3C)=O)C3=CC2=C1 VUHFMTBOSKAVGD-UHFFFAOYSA-N 0.000 claims description 4
- ZKPTVJPUVOPSSN-UHFFFAOYSA-N 7-(3-hydroxypropoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCO)=CC=C21 ZKPTVJPUVOPSSN-UHFFFAOYSA-N 0.000 claims description 4
- CZDOWLCKYCPNMU-UHFFFAOYSA-N 7-(4-oxopentoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)C)=CC=C21 CZDOWLCKYCPNMU-UHFFFAOYSA-N 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 4
- QJCPQIHEKQJMJL-UHFFFAOYSA-N methyl 4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoate Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)OC)=CC=C21 QJCPQIHEKQJMJL-UHFFFAOYSA-N 0.000 claims description 4
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 claims description 4
- 229940090181 propyl acetate Drugs 0.000 claims description 4
- AOAQFGRPXBJZPI-UHFFFAOYSA-N 7-(4-hydroxypentoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(O)C)=CC=C21 AOAQFGRPXBJZPI-UHFFFAOYSA-N 0.000 claims description 3
- HCLMLIZWYIZMGK-UHFFFAOYSA-N 7-(4-oxo-4-piperidin-1-ylbutoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2NC3=NC(O)=NC3=CC2=CC=1OCCCC(=O)N1CCCCC1 HCLMLIZWYIZMGK-UHFFFAOYSA-N 0.000 claims description 3
- JAODEWCDRHAJPF-UHFFFAOYSA-N 7-[4-(1-cyclohexyltetrazol-5-yl)butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 JAODEWCDRHAJPF-UHFFFAOYSA-N 0.000 claims description 3
- PSFRCKHLCWZSJR-UHFFFAOYSA-N 7-[4-(benzenesulfonyl)butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCCS(=O)(=O)C1=CC=CC=C1 PSFRCKHLCWZSJR-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- CVZAAYRCMFKBOJ-UHFFFAOYSA-N n-cycloheptyl-n-methyl-4-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCC(=O)N(C)C1CCCCCC1 CVZAAYRCMFKBOJ-UHFFFAOYSA-N 0.000 claims description 3
- HWFONEMQJJUUCU-UHFFFAOYSA-N n-cycloheptyl-n-methyl-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCC(=O)N(C)C1CCCCCC1 HWFONEMQJJUUCU-UHFFFAOYSA-N 0.000 claims description 3
- NAPKHDRXTZVUOK-UHFFFAOYSA-N n-cycloheptyl-n-methyl-5-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]pentanamide Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCCC(=O)N(C)C1CCCCCC1 NAPKHDRXTZVUOK-UHFFFAOYSA-N 0.000 claims description 3
- SFVRSCDYQRBUBX-UHFFFAOYSA-N n-cyclohexyl-n-methyl-5-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]pentanamide Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCCC(=O)N(C)C1CCCCC1 SFVRSCDYQRBUBX-UHFFFAOYSA-N 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- DFNDXJHNTNXDLS-UHFFFAOYSA-N (1-ethyl-2-oxo-3H-imidazo[4,5-b]quinolin-7-yl) ethaneperoxoate Chemical compound C(C)(=O)OOC1=CC=2C=C3C(=NC=2C=C1)NC(N3CC)=O DFNDXJHNTNXDLS-UHFFFAOYSA-N 0.000 claims description 2
- NEXQSNFNHKOAMU-UHFFFAOYSA-N 1-methyl-7-(4-oxo-4-piperidin-1-ylbutoxy)-3h-imidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCC(=O)N1CCCCC1 NEXQSNFNHKOAMU-UHFFFAOYSA-N 0.000 claims description 2
- ANBLGOPBKUCVNY-UHFFFAOYSA-N 2-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]acetic acid Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCC(=O)O)=CC=C21 ANBLGOPBKUCVNY-UHFFFAOYSA-N 0.000 claims description 2
- IYFJFKYCOWHMMW-UHFFFAOYSA-N 2-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]ethyl acetate Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCOC(=O)C)=CC=C21 IYFJFKYCOWHMMW-UHFFFAOYSA-N 0.000 claims description 2
- YVEQUTSPFYJJAS-UHFFFAOYSA-N 3-tert-butyl-5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxymethyl]-1,3-oxazolidin-2-one Chemical compound O1C(=O)N(C(C)(C)C)CC1COC1=CC=C(N=C2C(NC(=O)N2)=C2)C2=C1 YVEQUTSPFYJJAS-UHFFFAOYSA-N 0.000 claims description 2
- VDJBMWZCELLWPP-UHFFFAOYSA-N 4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]-n-pentan-3-ylbutanamide Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)NC(CC)CC)=CC=C21 VDJBMWZCELLWPP-UHFFFAOYSA-N 0.000 claims description 2
- AHNFHVODVZRNNS-UHFFFAOYSA-N 5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]pentanoic acid Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCCC(=O)O)=CC=C21 AHNFHVODVZRNNS-UHFFFAOYSA-N 0.000 claims description 2
- BJHINFNFMZFKMO-UHFFFAOYSA-N 7-(2-ethoxyethoxy)-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCOCC)=CC=C21 BJHINFNFMZFKMO-UHFFFAOYSA-N 0.000 claims description 2
- IIRDWOWRQLOSDT-UHFFFAOYSA-N 7-[2-hydroxy-3-(propan-2-ylamino)propoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCC(O)CNC(C)C)=CC=C21 IIRDWOWRQLOSDT-UHFFFAOYSA-N 0.000 claims description 2
- CXKZVQGXPZXMLT-UHFFFAOYSA-N 7-[3-(benzenesulfonyl)propoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCS(=O)(=O)C1=CC=CC=C1 CXKZVQGXPZXMLT-UHFFFAOYSA-N 0.000 claims description 2
- NHSCJGOJCUSYKC-UHFFFAOYSA-N 7-[3-(benzenesulfonyl)propoxy]-1-methyl-3h-imidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCS(=O)(=O)C1=CC=CC=C1 NHSCJGOJCUSYKC-UHFFFAOYSA-N 0.000 claims description 2
- WAEGLNICSZBTBF-UHFFFAOYSA-N 7-[4-oxo-4-(4-phenylpiperazin-1-yl)butoxy]-1,3-dihydroimidazo[4,5-b]quinolin-2-one Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCC(=O)N(CC1)CCN1C1=CC=CC=C1 WAEGLNICSZBTBF-UHFFFAOYSA-N 0.000 claims description 2
- 150000001414 amino alcohols Chemical class 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- FYTROBAKOHFNCC-UHFFFAOYSA-N ethyl 1-[4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)CCCOC1=CC=C(N=C2C(NC(=O)N2)=C2)C2=C1 FYTROBAKOHFNCC-UHFFFAOYSA-N 0.000 claims description 2
- IMWBJZZHCMTYMG-UHFFFAOYSA-N ethyl 2-[4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanoylamino]acetate Chemical compound N1=C2NC(=O)NC2=CC2=CC(OCCCC(=O)NCC(=O)OCC)=CC=C21 IMWBJZZHCMTYMG-UHFFFAOYSA-N 0.000 claims description 2
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- QTNSXEDSNVXNDG-UHFFFAOYSA-N n-cycloheptyl-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2NC3=NC(O)=NC3=CC2=CC=1OCCCC(=O)NC1CCCCCC1 QTNSXEDSNVXNDG-UHFFFAOYSA-N 0.000 claims description 2
- PTEGEICPLYKICS-UHFFFAOYSA-N n-cycloheptyl-n-methyl-5-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]pentanamide Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCCC(=O)N(C)C1CCCCCC1 PTEGEICPLYKICS-UHFFFAOYSA-N 0.000 claims description 2
- IEJDYNFNHADWGH-UHFFFAOYSA-N n-cyclohexyl-4-[(1-methyl-2-oxo-3h-imidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2N=C3NC(=O)N(C)C3=CC2=CC=1OCCCC(=O)NC1CCCCC1 IEJDYNFNHADWGH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims 2
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 description 162
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 120
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
- 239000000203 mixture Substances 0.000 description 83
- 238000004458 analytical method Methods 0.000 description 73
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 57
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- 229910052757 nitrogen Inorganic materials 0.000 description 32
- 239000007787 solid Substances 0.000 description 29
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 23
- 238000010992 reflux Methods 0.000 description 19
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 18
- 239000011630 iodine Substances 0.000 description 18
- 238000002425 crystallisation Methods 0.000 description 17
- 230000008025 crystallization Effects 0.000 description 17
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 17
- PNQYQNIOVAYJJG-UHFFFAOYSA-N 5-diethoxyphosphorylimidazolidine-2,4-dione Chemical compound CCOP(=O)(OCC)C1NC(=O)NC1=O PNQYQNIOVAYJJG-UHFFFAOYSA-N 0.000 description 16
- 239000000538 analytical sample Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 239000000463 material Substances 0.000 description 13
- 239000005909 Kieselgur Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 12
- 235000019345 sodium thiosulphate Nutrition 0.000 description 12
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 150000007513 acids Chemical class 0.000 description 10
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000543 intermediate Substances 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 238000011282 treatment Methods 0.000 description 9
- XLYPHUGUKGMURE-UHFFFAOYSA-N 5-hydroxy-2-nitrobenzaldehyde Chemical compound OC1=CC=C([N+]([O-])=O)C(C=O)=C1 XLYPHUGUKGMURE-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 229910002091 carbon monoxide Inorganic materials 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
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- SNZYABVPSGYRAZ-UHFFFAOYSA-N n-(cyclohexylmethyl)-4-[3-[(2,5-dioxoimidazolidin-4-ylidene)methyl]-4-nitrophenoxy]butanamide Chemical compound C1=C(C=C2C(NC(=O)N2)=O)C([N+](=O)[O-])=CC=C1OCCCC(=O)NCC1CCCCC1 SNZYABVPSGYRAZ-UHFFFAOYSA-N 0.000 description 1
- BDBZBLKPDVRCQY-UHFFFAOYSA-N n-(cyclohexylmethyl)-4-[3-[(2,5-dioxoimidazolidin-4-ylidene)methyl]-4-nitrophenoxy]butanamide;hydrate Chemical compound O.C1=C(C=C2C(NC(=O)N2)=O)C([N+](=O)[O-])=CC=C1OCCCC(=O)NCC1CCCCC1 BDBZBLKPDVRCQY-UHFFFAOYSA-N 0.000 description 1
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- AUZJVEDTLNZEHH-UHFFFAOYSA-N n-cyclohexyl-4-[(2-oxo-1,3-dihydroimidazo[4,5-b]quinolin-7-yl)oxy]butanamide Chemical compound C=1C=C2N=C3NC(=O)NC3=CC2=CC=1OCCCC(=O)NC1CCCCC1 AUZJVEDTLNZEHH-UHFFFAOYSA-N 0.000 description 1
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- FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
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- 230000009090 positive inotropic effect Effects 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
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- 125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- HUAZGNHGCJGYNP-UHFFFAOYSA-N propyl butyrate Chemical compound CCCOC(=O)CCC HUAZGNHGCJGYNP-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- 235000010487 tragacanth Nutrition 0.000 description 1
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- 150000003624 transition metals Chemical class 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/866,813 US4775674A (en) | 1986-05-23 | 1986-05-23 | Imidazoquinolinylether derivatives useful as phosphodiesterase and blood aggregation inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE3717291A1 true DE3717291A1 (de) | 1987-11-26 |
Family
ID=25348473
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19873717291 Withdrawn DE3717291A1 (de) | 1986-05-23 | 1987-05-22 | Imidazochinolinyletherderivate, verfahren zu deren herstellung und diese verbindungen enthaltende pharmazeutische mittel |
Country Status (24)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2127273C1 (ru) * | 1991-10-30 | 1999-03-10 | Жансен Фармасетика Н.В. | Производное 1,3-дигидро-2h-имидазо/4,5-b/хинолин-2-она в качестве ингибитора фосфодиэстеразы, способ его получения, промежуточные для него, фармацевтическая композиция и способ ее получения |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1306260C (en) * | 1985-10-18 | 1992-08-11 | Shionogi & Co., Ltd. | Condensed imidazopyridine derivatives |
| JPH01189791A (ja) * | 1988-01-26 | 1989-07-28 | New Japan Radio Co Ltd | 非接触ｉｄカード |
| US4943573A (en) * | 1989-11-01 | 1990-07-24 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyloxyalkanoic acid amides with enhanced water solubility |
| US5262540A (en) * | 1989-12-20 | 1993-11-16 | Bristol-Myers Squibb Company | [2(4,5-diaryl-2 oxazoyl substituted phenoxy alkanoic acid and esters |
| US5348960A (en) * | 1992-04-03 | 1994-09-20 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyl oxy alkyl tetrazolyl piperidine derivatives |
| US5187188A (en) * | 1992-04-03 | 1993-02-16 | Bristol-Myers Squibb Company | Oxazole carboxylic acid derivatives |
| US5552267A (en) * | 1992-04-03 | 1996-09-03 | The Trustees Of Columbia University In The City Of New York | Solution for prolonged organ preservation |
| US5196428A (en) * | 1992-04-03 | 1993-03-23 | Bristol-Myers Squibb Company | Imidazo[4,5-b]qinolinyl oxy alkyl ureas |
| US5208237A (en) * | 1992-04-03 | 1993-05-04 | Bristol-Meyers Squibb Company | 7-oxypropylsulfonamido-imidazo[4,5-b]quinolin-2-ones |
| US5158958A (en) * | 1992-04-03 | 1992-10-27 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyl oxy alkyl sulfonyl piperidine derivatives |
| TW593317B (en) | 1993-06-21 | 2004-06-21 | Janssen Pharmaceutica Nv | Positive cardiac inotropic and lusitropic pyrroloquinolinone derivatives |
| US6756382B2 (en) * | 1999-06-10 | 2004-06-29 | 3M Innovative Properties Company | Amide substituted imidazoquinolines |
| US6541485B1 (en) | 1999-06-10 | 2003-04-01 | 3M Innovative Properties Company | Urea substituted imidazoquinolines |
| US6331539B1 (en) * | 1999-06-10 | 2001-12-18 | 3M Innovative Properties Company | Sulfonamide and sulfamide substituted imidazoquinolines |
| US6573273B1 (en) | 1999-06-10 | 2003-06-03 | 3M Innovative Properties Company | Urea substituted imidazoquinolines |
| JP4767429B2 (ja) * | 2001-03-02 | 2011-09-07 | 株式会社クラレ | 架橋剤および架橋性重合体 |
| MXPA05005661A (es) * | 2002-11-27 | 2005-11-23 | Artesian Therapeutics Inc | Compuestos con actividad antagonista o antagonista parcial mixta inhibidora de fosfodiesterasa y beta-adrenergica para el tratamiento de insuficiencia cardiaca. |
| MXPA06001669A (es) | 2003-08-12 | 2006-04-28 | 3M Innovative Properties Co | Compuestos que contienen imidazo-oxima sustituidos. |
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| WO2005023190A2 (en) | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for cd5+ b cell lymphoma |
| BRPI0414856A (pt) | 2003-10-03 | 2006-11-21 | 3M Innovative Properties Co | imidazoquinolinas alcóxi-substituìdas |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| US8598192B2 (en) | 2003-11-14 | 2013-12-03 | 3M Innovative Properties Company | Hydroxylamine substituted imidazoquinolines |
| WO2005048933A2 (en) | 2003-11-14 | 2005-06-02 | 3M Innovative Properties Company | Oxime substituted imidazo ring compounds |
| NZ547467A (en) | 2003-11-25 | 2010-06-25 | 3M Innovative Properties Co | Substituted imidazo ring system and methods |
| US8802853B2 (en) | 2003-12-29 | 2014-08-12 | 3M Innovative Properties Company | Arylalkenyl and arylalkynyl substituted imidazoquinolines |
| US8735421B2 (en) | 2003-12-30 | 2014-05-27 | 3M Innovative Properties Company | Imidazoquinolinyl sulfonamides |
| CA2559863A1 (en) | 2004-03-24 | 2005-10-13 | 3M Innovative Properties Company | Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines |
| WO2005123080A2 (en) | 2004-06-15 | 2005-12-29 | 3M Innovative Properties Company | Nitrogen-containing heterocyclyl substituted imidazoquinolines and imidazonaphthyridines |
| US7897609B2 (en) | 2004-06-18 | 2011-03-01 | 3M Innovative Properties Company | Aryl substituted imidazonaphthyridines |
| WO2006009826A1 (en) | 2004-06-18 | 2006-01-26 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted thiazoloquinolines and thiazolonaphthyridines |
| WO2006065280A2 (en) | 2004-06-18 | 2006-06-22 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and methods |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3932407A (en) * | 1973-11-19 | 1976-01-13 | Bristol-Myers Company | Optionally substituted 1,2,3,5-tetrahydroimidezo(2,1-b)-quinazolin-2-ones and 6(H)-1,2,3,4-tetrahydropyimido(2,1-b)quinazolin-2-ones |
| NL7807507A (nl) * | 1977-07-25 | 1979-01-29 | Hoffmann La Roche | Tricyclische verbindingen. |
| IL62402A0 (en) * | 1980-03-24 | 1981-05-20 | Sterling Drug Inc | Imidazo(4,5-b)pyridines,their preparation and pharmaceutical compositions containing them |
| US4490371A (en) * | 1983-02-16 | 1984-12-25 | Syntex (U.S.A.) Inc. | N,N-Disubstituted-(2-oxo-1,2,3,5-tetrahydroimidazo-[2,1-B]quinazolinyl)oxyalkylamides |
| JPS604186A (ja) * | 1983-06-21 | 1985-01-10 | Dai Ichi Seiyaku Co Ltd | イミダゾキナゾリン化合物 |
| JPS6028979A (ja) * | 1983-07-14 | 1985-02-14 | Dai Ichi Seiyaku Co Ltd | イミダゾキナゾリン類化合物 |
| NO164654C (no) * | 1984-02-15 | 1990-10-31 | Syntex Inc | Analogifremgangsmaate for fremstilling av terapeutisk aktive (2-okso-1,2,3,5-tetrahydroimidazo (2,1-b)kinazolinyl)-oksylakylamider. |
| US4668686A (en) * | 1985-04-25 | 1987-05-26 | Bristol-Myers Company | Imidazoquinoline antithrombrogenic cardiotonic agents |
-
1986
- 1986-05-23 US US06/866,813 patent/US4775674A/en not_active Expired - Fee Related
-
1987
- 1987-05-15 AU AU72993/87A patent/AU603577B2/en not_active Ceased
- 1987-05-18 NZ NZ220345A patent/NZ220345A/xx unknown
- 1987-05-19 ZA ZA873583A patent/ZA873583B/xx unknown
- 1987-05-19 GB GB8711839A patent/GB2190676B/en not_active Expired - Fee Related
- 1987-05-20 FI FI872220A patent/FI86723C/fi not_active IP Right Cessation
- 1987-05-21 GR GR870803A patent/GR870803B/el unknown
- 1987-05-21 IL IL82612A patent/IL82612A0/xx not_active IP Right Cessation
- 1987-05-22 KR KR1019870005066A patent/KR900008567B1/ko not_active Expired
- 1987-05-22 NL NL8701226A patent/NL8701226A/nl not_active Application Discontinuation
- 1987-05-22 DE DE19873717291 patent/DE3717291A1/de not_active Withdrawn
- 1987-05-22 SE SE8702158A patent/SE465163B/sv not_active IP Right Cessation
- 1987-05-22 PT PT84938A patent/PT84938B/pt unknown
- 1987-05-22 ES ES8701506A patent/ES2005588A6/es not_active Expired
- 1987-05-22 IT IT20650/87A patent/IT1205031B/it active
- 1987-05-22 CA CA000537720A patent/CA1289137C/en not_active Expired - Fee Related
- 1987-05-22 AT AT1320/87A patent/AT392790B/de not_active IP Right Cessation
- 1987-05-22 JP JP62125642A patent/JPS62283972A/ja active Pending
- 1987-05-22 LU LU86896A patent/LU86896A1/fr unknown
- 1987-05-22 FR FR878707252A patent/FR2603586B1/fr not_active Expired - Fee Related
- 1987-05-22 BE BE8700581A patent/BE1002033A4/fr not_active IP Right Cessation
- 1987-05-22 HU HU872295A patent/HU197570B/hu not_active IP Right Cessation
- 1987-05-22 DK DK263587A patent/DK166084C/da active
- 1987-05-25 CH CH2018/87A patent/CH675246A5/de not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2127273C1 (ru) * | 1991-10-30 | 1999-03-10 | Жансен Фармасетика Н.В. | Производное 1,3-дигидро-2h-имидазо/4,5-b/хинолин-2-она в качестве ингибитора фосфодиэстеразы, способ его получения, промежуточные для него, фармацевтическая композиция и способ ее получения |
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