PT84938B - Processo para a preparacao de derivados do eter imidazoquinolinilico - Google Patents
Processo para a preparacao de derivados do eter imidazoquinolinilico Download PDFInfo
- Publication number
- PT84938B PT84938B PT84938A PT8493887A PT84938B PT 84938 B PT84938 B PT 84938B PT 84938 A PT84938 A PT 84938A PT 8493887 A PT8493887 A PT 8493887A PT 84938 B PT84938 B PT 84938B
- Authority
- PT
- Portugal
- Prior art keywords
- dihydro
- imidazo
- oxo
- pharmaceutically acceptable
- acceptable salts
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 130
- 238000002360 preparation method Methods 0.000 title claims description 46
- 150000001875 compounds Chemical class 0.000 claims abstract description 149
- -1 quinolinyl ether derivatives Chemical class 0.000 claims abstract description 87
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 54
- 150000002148 esters Chemical class 0.000 claims abstract description 22
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 17
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 230000008569 process Effects 0.000 claims description 98
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 69
- 150000003839 salts Chemical class 0.000 claims description 61
- 239000002253 acid Substances 0.000 claims description 55
- 125000004432 carbon atom Chemical group C* 0.000 claims description 35
- 229910052740 iodine Inorganic materials 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 18
- 229940091173 hydantoin Drugs 0.000 claims description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
- 125000004043 oxo group Chemical group O=* 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 150000001469 hydantoins Chemical class 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 150000002576 ketones Chemical class 0.000 claims description 7
- 150000001408 amides Chemical class 0.000 claims description 6
- 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 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 230000002829 reductive effect Effects 0.000 claims description 6
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 5
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 5
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 4
- 125000001137 3-hydroxypropoxy group Chemical group [H]OC([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 4
- 239000004471 Glycine Substances 0.000 claims description 4
- 239000012458 free base Substances 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 150000001414 amino alcohols Chemical class 0.000 claims description 2
- 229940090181 propyl acetate Drugs 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 45
- VJMAITQRABEEKP-UHFFFAOYSA-N [6-(phenylmethoxymethyl)-1,4-dioxan-2-yl]methyl acetate Chemical compound O1C(COC(=O)C)COCC1COCC1=CC=CC=C1 VJMAITQRABEEKP-UHFFFAOYSA-N 0.000 claims 2
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims 1
- 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 claims 1
- 210000001772 blood platelet Anatomy 0.000 abstract description 23
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 abstract description 7
- 239000002571 phosphodiesterase inhibitor Substances 0.000 abstract description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract description 4
- 239000000496 cardiotonic agent Substances 0.000 abstract description 4
- 239000003112 inhibitor Substances 0.000 abstract description 4
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- 150000002367 halogens Chemical group 0.000 abstract description 2
- 150000002431 hydrogen Chemical group 0.000 abstract 2
- 150000003857 carboxamides Chemical class 0.000 abstract 1
- 125000004663 dialkyl amino group Chemical group 0.000 abstract 1
- 150000002169 ethanolamines Chemical class 0.000 abstract 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 abstract 1
- 125000003831 tetrazolyl group Chemical group 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 description 151
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 111
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- 239000000203 mixture Substances 0.000 description 87
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 238000004458 analytical method Methods 0.000 description 61
- 239000000243 solution Substances 0.000 description 56
- 239000000460 chlorine Substances 0.000 description 53
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- 238000005481 NMR spectroscopy Methods 0.000 description 41
- 238000002844 melting Methods 0.000 description 39
- 230000008018 melting Effects 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- 238000010992 reflux Methods 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 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 22
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 20
- 230000004520 agglutination Effects 0.000 description 17
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 16
- 239000000538 analytical sample Substances 0.000 description 16
- 239000011630 iodine Substances 0.000 description 16
- 238000011282 treatment Methods 0.000 description 16
- 238000002425 crystallisation Methods 0.000 description 15
- 230000008025 crystallization Effects 0.000 description 15
- 230000036961 partial effect Effects 0.000 description 15
- 150000003254 radicals Chemical class 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000002244 precipitate Substances 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
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 238000005984 hydrogenation reaction Methods 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 9
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 9
- 150000007513 acids Chemical class 0.000 description 9
- 229910002091 carbon monoxide Inorganic materials 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- PNQYQNIOVAYJJG-UHFFFAOYSA-N 5-diethoxyphosphorylimidazolidine-2,4-dione Chemical compound CCOP(=O)(OCC)C1NC(=O)NC1=O PNQYQNIOVAYJJG-UHFFFAOYSA-N 0.000 description 8
- 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
- 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 8
- 239000000284 extract Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 5
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 230000002152 alkylating effect Effects 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000000297 inotrophic effect Effects 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical group C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- RHYBFKMFHLPQPH-UHFFFAOYSA-N N-methylhydantoin Chemical compound CN1CC(=O)NC1=O RHYBFKMFHLPQPH-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 4
- 210000004623 platelet-rich plasma Anatomy 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical group CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- UIOAQJNADLELPQ-UHFFFAOYSA-N C[C]1OCCO1 Chemical group C[C]1OCCO1 UIOAQJNADLELPQ-UHFFFAOYSA-N 0.000 description 3
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- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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- 230000009471 action Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
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- 150000001450 anions Chemical class 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 3
- 150000001721 carbon Chemical group 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003245 coal Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000003456 ion exchange resin Substances 0.000 description 3
- 229920003303 ion-exchange polymer Polymers 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 244000144985 peep Species 0.000 description 3
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- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 3
- NYNBIZMIFBGAJF-UHFFFAOYSA-N (2,5-dioxoimidazolidin-4-yl)phosphonic acid Chemical compound OP(O)(=O)C1NC(=O)NC1=O NYNBIZMIFBGAJF-UHFFFAOYSA-N 0.000 description 2
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- UUIQMZJEGPQKFD-UHFFFAOYSA-N Methyl butyrate Chemical compound CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000282339 Mustela Species 0.000 description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 2
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
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- HUAZGNHGCJGYNP-UHFFFAOYSA-N propyl butyrate Chemical compound CCCOC(=O)CCC HUAZGNHGCJGYNP-UHFFFAOYSA-N 0.000 description 1
- GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 description 1
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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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (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 (2)
| Publication Number | Publication Date |
|---|---|
| PT84938A PT84938A (en) | 1987-06-01 |
| PT84938B true PT84938B (pt) | 1990-02-08 |
Family
ID=25348473
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT84938A PT84938B (pt) | 1986-05-23 | 1987-05-22 | Processo para a preparacao de derivados do eter imidazoquinolinilico |
Country Status (24)
Families Citing this family (57)
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| 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 |
| PH31245A (en) * | 1991-10-30 | 1998-06-18 | Janssen Pharmaceutica Nv | 1,3-Dihydro-2H-imidazoÄ4,5-BÜ-quinolin-2-one derivatives. |
| US5196428A (en) * | 1992-04-03 | 1993-03-23 | Bristol-Myers Squibb Company | Imidazo[4,5-b]qinolinyl oxy alkyl ureas |
| US5348960A (en) * | 1992-04-03 | 1994-09-20 | Bristol-Myers Squibb Company | Imidazo[4,5-b]quinolinyl oxy alkyl tetrazolyl piperidine derivatives |
| 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 |
| US5552267A (en) * | 1992-04-03 | 1996-09-03 | The Trustees Of Columbia University In The City Of New York | Solution for prolonged organ preservation |
| US5187188A (en) * | 1992-04-03 | 1993-02-16 | Bristol-Myers Squibb Company | Oxazole carboxylic acid derivatives |
| TW593317B (en) | 1993-06-21 | 2004-06-21 | Janssen Pharmaceutica Nv | Positive cardiac inotropic and lusitropic pyrroloquinolinone derivatives |
| US6573273B1 (en) | 1999-06-10 | 2003-06-03 | 3M Innovative Properties Company | Urea 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 |
| US6756382B2 (en) * | 1999-06-10 | 2004-06-29 | 3M Innovative Properties Company | Amide 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 |
| WO2004050657A2 (en) * | 2002-11-27 | 2004-06-17 | Artesian Therapeutics, Inc. | COMPOUNDS WITH MIXED PDE-INHIBITORY AND β-ADRENERGIC ANTAGONIST OR PARTIAL AGONIST ACTIVITY FOR TREATMENT OF HEART FAILURE |
| US8673932B2 (en) | 2003-08-12 | 2014-03-18 | 3M Innovative Properties Company | Oxime substituted imidazo-containing compounds |
| JP5128815B2 (ja) | 2003-08-27 | 2013-01-23 | スリーエム イノベイティブ プロパティズ カンパニー | アリールオキシ置換およびアリールアルキレンオキシ置換イミダゾキノリン |
| WO2005023190A2 (en) | 2003-09-05 | 2005-03-17 | 3M Innovative Properties Company | Treatment for cd5+ b cell lymphoma |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| ES2544477T3 (es) | 2003-10-03 | 2015-08-31 | 3M Innovative Properties Company | Imidazoquinolinas sustituidas con alcoxi |
| EP1682544A4 (en) | 2003-11-14 | 2009-05-06 | 3M Innovative Properties Co | HYDROXYLAMINE SUBSTITUTED IMIDAZO RING COMPOUNDS |
| CN1906193A (zh) | 2003-11-14 | 2007-01-31 | 3M创新有限公司 | 肟取代的咪唑环化合物 |
| MXPA06005910A (es) | 2003-11-25 | 2006-08-23 | 3M Innovative Properties Co | Sistemas de anillo imidazo sustituido y metodos. |
| EP1701955A1 (en) | 2003-12-29 | 2006-09-20 | 3M Innovative Properties Company | Arylalkenyl and arylalkynyl substituted imidazoquinolines |
| JP2007517044A (ja) | 2003-12-30 | 2007-06-28 | スリーエム イノベイティブ プロパティズ カンパニー | イミダゾキノリニル、イミダゾピリジニル、およびイミダゾナフチリジニルスルホンアミド |
| 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 |
| US7915281B2 (en) | 2004-06-18 | 2011-03-29 | 3M Innovative Properties Company | Isoxazole, dihydroisoxazole, and oxadiazole substituted imidazo ring compounds and method |
| WO2006038923A2 (en) | 2004-06-18 | 2006-04-13 | 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 |
| EP1831221B1 (en) | 2004-12-30 | 2012-08-08 | 3M Innovative Properties Company | Substituted chiral fused 1,2 imidazo 4,5-c ring compounds |
| ES2392647T3 (es) | 2004-12-30 | 2012-12-12 | 3M Innovative Properties Company | Compuestos tetracíclicos quirales que inducen la biosíntesis de interferón |
| JP2008530022A (ja) | 2005-02-04 | 2008-08-07 | コーリー ファーマシューティカル グループ，インコーポレイテッド | 免疫反応調節物質を含む水性ゲル処方物 |
| WO2006086634A2 (en) | 2005-02-11 | 2006-08-17 | Coley Pharmaceutical Group, Inc. | Oxime and hydroxylamine substituted imidazo[4,5-c] ring compounds and methods |
| AU2006232377A1 (en) | 2005-04-01 | 2006-10-12 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridine-1,4-diamines and analogs thereof |
| JP2008538550A (ja) | 2005-04-01 | 2008-10-30 | コーリー ファーマシューティカル グループ，インコーポレイテッド | ウイルス感染および腫瘍性疾患を処置するためのサイトカイン生合成の調節因子としての１−置換ピラゾロ（３，４−ｃ）環状化合物 |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| CA2620333A1 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| AU2006304787A1 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
| EP2314289A1 (en) | 2005-10-31 | 2011-04-27 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| JP2009536667A (ja) | 2006-05-09 | 2009-10-15 | ブレインセルス，インコーポレイティド | ５ｈｔ受容体介在性の神経新生 |
| EP2021000A2 (en) | 2006-05-09 | 2009-02-11 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| WO2008008432A2 (en) | 2006-07-12 | 2008-01-17 | Coley Pharmaceutical Group, Inc. | Substituted chiral fused( 1,2) imidazo (4,5-c) ring compounds and methods |
| US8227603B2 (en) | 2006-08-01 | 2012-07-24 | Cytokinetics, Inc. | Modulating skeletal muscle |
| EP2583970B1 (en) | 2006-08-02 | 2015-10-14 | Cytokinetics, Inc. | Certain chemical entities, compositions and methods comprising imidazopyrimidines |
| US8299248B2 (en) | 2006-08-02 | 2012-10-30 | Cytokinetics, Incorporated | Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use |
| MX2009002496A (es) | 2006-09-08 | 2009-07-10 | Braincells Inc | Combinaciones que contienen un derivado de 4-acilaminopiridina. |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| US7851484B2 (en) | 2007-03-30 | 2010-12-14 | Cytokinetics, Inc. | Certain chemical entities, compositions, and methods |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| EP2731611B1 (en) | 2011-07-13 | 2019-09-18 | Cytokinetics, Inc. | Combination therapie for als |
| WO2013106547A1 (en) | 2012-01-10 | 2013-07-18 | President And Fellows Of Harvard College | Beta-cell replication promoting compounds and methods of their use |
| EP4678641A1 (en) * | 2023-01-13 | 2026-01-14 | Shanghai Helioson Pharmaceutical Co., Ltd. | Quinolinone compound and naphthyridinone compound and use thereof |
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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 |
| NZ211117A (en) * | 1984-02-15 | 1987-10-30 | Syntex Inc | Fused tetrahydroimidazo-(2,1-b)quinazoline derivatives and pharmaceutical compositions |
| 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 GB GB8711839A patent/GB2190676B/en not_active Expired - Fee Related
- 1987-05-19 ZA ZA873583A patent/ZA873583B/xx unknown
- 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 PT PT84938A patent/PT84938B/pt unknown
- 1987-05-22 AT AT1320/87A patent/AT392790B/de not_active IP Right Cessation
- 1987-05-22 FR FR878707252A patent/FR2603586B1/fr not_active Expired - Fee Related
- 1987-05-22 DK DK263587A patent/DK166084C/da active
- 1987-05-22 KR KR1019870005066A patent/KR900008567B1/ko not_active Expired
- 1987-05-22 DE DE19873717291 patent/DE3717291A1/de not_active Withdrawn
- 1987-05-22 ES ES8701506A patent/ES2005588A6/es not_active Expired
- 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 NL NL8701226A patent/NL8701226A/nl not_active Application Discontinuation
- 1987-05-22 SE SE8702158A patent/SE465163B/sv 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 CA CA000537720A patent/CA1289137C/en not_active Expired - Fee Related
- 1987-05-22 IT IT20650/87A patent/IT1205031B/it active
- 1987-05-25 CH CH2018/87A patent/CH675246A5/de not_active IP Right Cessation
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