AU664643B2 - Azaquinoxalines, processes for their preparation and their use - Google Patents
Azaquinoxalines, processes for their preparation and their use Download PDFInfo
- Publication number
- AU664643B2 AU664643B2 AU47553/93A AU4755393A AU664643B2 AU 664643 B2 AU664643 B2 AU 664643B2 AU 47553/93 A AU47553/93 A AU 47553/93A AU 4755393 A AU4755393 A AU 4755393A AU 664643 B2 AU664643 B2 AU 664643B2
- Authority
- AU
- Australia
- Prior art keywords
- alkyl
- hydroxyl
- alkoxy
- chlorine
- fluorine
- 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.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims description 24
- 238000002360 preparation method Methods 0.000 title claims description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 102
- 229910052721 tungsten Inorganic materials 0.000 claims abstract description 12
- 229910052720 vanadium Inorganic materials 0.000 claims abstract description 12
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 12
- 241000700605 Viruses Species 0.000 claims abstract description 3
- -1 acylaniino Chemical group 0.000 claims description 329
- 239000000460 chlorine Substances 0.000 claims description 152
- 229910052801 chlorine Inorganic materials 0.000 claims description 152
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 150
- 239000011737 fluorine Substances 0.000 claims description 147
- 229910052731 fluorine Inorganic materials 0.000 claims description 147
- 125000001153 fluoro group Chemical group F* 0.000 claims description 126
- 125000003545 alkoxy group Chemical group 0.000 claims description 124
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 109
- 125000004043 oxo group Chemical group O=* 0.000 claims description 87
- 229910052794 bromium Inorganic materials 0.000 claims description 74
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 72
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 72
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 72
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 71
- 125000004414 alkyl thio group Chemical group 0.000 claims description 64
- 125000003282 alkyl amino group Chemical group 0.000 claims description 63
- 125000004423 acyloxy group Chemical group 0.000 claims description 61
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 60
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 58
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 57
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 44
- 238000006243 chemical reaction Methods 0.000 claims description 34
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 34
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 34
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 29
- 150000003254 radicals Chemical class 0.000 claims description 29
- 229910052799 carbon Inorganic materials 0.000 claims description 28
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 25
- 239000001301 oxygen Substances 0.000 claims description 25
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 22
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 20
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 20
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000004442 acylamino group Chemical group 0.000 claims description 13
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 239000011593 sulfur Chemical group 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 8
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 8
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 8
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 7
- 125000001769 aryl amino group Chemical group 0.000 claims description 7
- 125000005110 aryl thio group Chemical group 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000005015 aryl alkynyl group Chemical group 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 6
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 6
- 150000002829 nitrogen Chemical class 0.000 claims description 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 5
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 5
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical group [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 4
- 125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 4
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 4
- 125000005225 alkynyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 4
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 claims description 4
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 4
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 125000001326 naphthylalkyl group Chemical group 0.000 claims description 4
- 229910052711 selenium Inorganic materials 0.000 claims description 4
- 239000011669 selenium Chemical group 0.000 claims description 4
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 4
- 238000005987 sulfurization reaction Methods 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 3
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 3
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 101100450129 Caenorhabditis elegans hal-3 gene Proteins 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
- 230000000840 anti-viral effect Effects 0.000 claims description 2
- 229950005228 bromoform Drugs 0.000 claims description 2
- 125000002837 carbocyclic group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000005932 reductive alkylation reaction Methods 0.000 claims description 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 2
- 229940060037 fluorine Drugs 0.000 claims 75
- 235000019000 fluorine Nutrition 0.000 claims 75
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 3
- 229960005419 nitrogen Drugs 0.000 claims 3
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims 1
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
- 235000009917 Crataegus X brevipes Nutrition 0.000 claims 1
- 235000013204 Crataegus X haemacarpa Nutrition 0.000 claims 1
- 235000009685 Crataegus X maligna Nutrition 0.000 claims 1
- 235000009444 Crataegus X rubrocarnea Nutrition 0.000 claims 1
- 235000009486 Crataegus bullatus Nutrition 0.000 claims 1
- 235000017181 Crataegus chrysocarpa Nutrition 0.000 claims 1
- 235000009682 Crataegus limnophila Nutrition 0.000 claims 1
- 235000004423 Crataegus monogyna Nutrition 0.000 claims 1
- 240000000171 Crataegus monogyna Species 0.000 claims 1
- 235000002313 Crataegus paludosa Nutrition 0.000 claims 1
- 235000009840 Crataegus x incaedua Nutrition 0.000 claims 1
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical group CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 claims 1
- 241000534944 Thia Species 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 210000002837 heart atrium Anatomy 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 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
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
- 238000002844 melting Methods 0.000 description 53
- 230000008018 melting Effects 0.000 description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 22
- 229910002027 silica gel Inorganic materials 0.000 description 22
- 239000000203 mixture Substances 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 229910052938 sodium sulfate Inorganic materials 0.000 description 9
- 235000011152 sodium sulphate Nutrition 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 238000006555 catalytic reaction Methods 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- 239000007868 Raney catalyst Substances 0.000 description 7
- 229910000564 Raney nickel Inorganic materials 0.000 description 7
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 102100034343 Integrase Human genes 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000001340 alkali metals Chemical class 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 150000001298 alcohols Chemical class 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- WZCKOKPKQZIGNU-UHFFFAOYSA-N 1h-naphthalen-2-one Chemical compound C1=CC=C2C=CC(=O)CC2=C1 WZCKOKPKQZIGNU-UHFFFAOYSA-N 0.000 description 4
- OZEJKXBTUYFTHF-UHFFFAOYSA-N 3-phenyl-3,4-dihydro-1h-pyrido[2,3-b]pyrazin-2-one Chemical compound O=C1NC2=CC=CN=C2NC1C1=CC=CC=C1 OZEJKXBTUYFTHF-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 210000004698 lymphocyte Anatomy 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- AMMGCGVWJMRTQI-UHFFFAOYSA-N prop-1-en-2-yl carbonochloridate Chemical compound CC(=C)OC(Cl)=O AMMGCGVWJMRTQI-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- SHCWQWRTKPNTEM-UHFFFAOYSA-N 2,6-dichloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=C(Cl)N=C1Cl SHCWQWRTKPNTEM-UHFFFAOYSA-N 0.000 description 3
- WQKHERPPDYPMNX-UHFFFAOYSA-N 6-chloro-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(Cl)=CC=C21 WQKHERPPDYPMNX-UHFFFAOYSA-N 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- 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 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 3
- 229910001863 barium hydroxide Inorganic materials 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
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- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- BHFLUDRTVIDDOR-MRVPVSSYSA-N methyl (2r)-2-amino-2-phenylacetate Chemical compound COC(=O)[C@H](N)C1=CC=CC=C1 BHFLUDRTVIDDOR-MRVPVSSYSA-N 0.000 description 1
- KTMOZZKFOZPLBJ-QMMMGPOBSA-N methyl (2s)-2-(pyridin-2-ylmethylamino)propanoate Chemical compound COC(=O)[C@H](C)NCC1=CC=CC=N1 KTMOZZKFOZPLBJ-QMMMGPOBSA-N 0.000 description 1
- IOMFKPFJYISUMW-JTQLQIEISA-N methyl (2s)-2-[(6-chloro-3-nitropyridin-2-yl)-(pyridin-2-ylmethyl)amino]propanoate Chemical compound N=1C(Cl)=CC=C([N+]([O-])=O)C=1N([C@@H](C)C(=O)OC)CC1=CC=CC=N1 IOMFKPFJYISUMW-JTQLQIEISA-N 0.000 description 1
- QEJGUCIALDACCS-YFKPBYRVSA-N methyl (2s)-2-[(6-chloro-3-nitropyridin-2-yl)amino]propanoate Chemical compound COC(=O)[C@H](C)NC1=NC(Cl)=CC=C1[N+]([O-])=O QEJGUCIALDACCS-YFKPBYRVSA-N 0.000 description 1
- BHFLUDRTVIDDOR-QMMMGPOBSA-N methyl (2s)-2-amino-2-phenylacetate Chemical compound COC(=O)[C@@H](N)C1=CC=CC=C1 BHFLUDRTVIDDOR-QMMMGPOBSA-N 0.000 description 1
- IYUKFAFDFHZKPI-DFWYDOINSA-N methyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)N IYUKFAFDFHZKPI-DFWYDOINSA-N 0.000 description 1
- SQGLAIFTDOIHOC-UHFFFAOYSA-N methyl 2-[(6-methoxy-3-nitropyridin-2-yl)amino]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)NC1=NC(OC)=CC=C1[N+]([O-])=O SQGLAIFTDOIHOC-UHFFFAOYSA-N 0.000 description 1
- NVWZNEDLYYLQJC-UHFFFAOYSA-N methyl 2-amino-2-methylpropanoate;hydrochloride Chemical compound Cl.COC(=O)C(C)(C)N NVWZNEDLYYLQJC-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 150000003833 nucleoside derivatives Chemical class 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- LMAZKPOSWVOFGY-FBAUPLQOSA-N orine Natural products CO[C@H]1C[C@H](O[C@H]2CC[C@]3(C)[C@H]4C[C@@H](OC(=O)C=Cc5ccccc5)[C@]6(C)[C@@](O)(CC[C@]6(O)[C@]4(O)CC=C3C2)[C@H](C)OC(=O)C=Cc7ccccc7)O[C@H](C)[C@H]1O LMAZKPOSWVOFGY-FBAUPLQOSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical class C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 230000001885 phytohemagglutinin Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- INJWKFFYHIOYEF-ZETCQYMHSA-N prop-1-en-2-yl (3s)-6-chloro-3-methyl-2-oxo-3,4-dihydropyrido[2,3-b]pyrazine-1-carboxylate Chemical compound ClC1=CC=C2N(C(=O)OC(C)=C)C(=O)[C@H](C)NC2=N1 INJWKFFYHIOYEF-ZETCQYMHSA-N 0.000 description 1
- DKUYWRUJESGGQK-UHFFFAOYSA-N prop-1-en-2-yl 2-chloro-7-methyl-6-sulfanylidene-5,7-dihydropteridine-8-carboxylate Chemical compound ClC1=NC=C2NC(=S)C(C)N(C(=O)OC(C)=C)C2=N1 DKUYWRUJESGGQK-UHFFFAOYSA-N 0.000 description 1
- ZOTNDAFZKNKZLT-UHFFFAOYSA-N prop-1-en-2-yl 3,6-dimethyl-2-sulfanylidene-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound CC1=CC=C2NC(=S)C(C)N(C(=O)OC(C)=C)C2=N1 ZOTNDAFZKNKZLT-UHFFFAOYSA-N 0.000 description 1
- UNFQPHYKBMLNRJ-UHFFFAOYSA-N prop-1-en-2-yl 3-methyl-2-oxo-3,4-dihydropyrido[2,3-b]pyrazine-1-carboxylate Chemical compound C(=C)(C)OC(=O)N1C(C(NC2=NC=CC=C12)C)=O UNFQPHYKBMLNRJ-UHFFFAOYSA-N 0.000 description 1
- FYDFQDPHWMKQLK-UHFFFAOYSA-N prop-1-en-2-yl 6-methyl-7-sulfanylidene-6,8-dihydropteridine-5-carboxylate Chemical compound N1=CN=C2NC(=S)C(C)N(C(=O)OC(C)=C)C2=C1 FYDFQDPHWMKQLK-UHFFFAOYSA-N 0.000 description 1
- UXYGGBNOJOHSTD-UHFFFAOYSA-N propan-2-yl 2-oxo-3-phenyl-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound O=C1NC2=CC=CN=C2N(C(=O)OC(C)C)C1C1=CC=CC=C1 UXYGGBNOJOHSTD-UHFFFAOYSA-N 0.000 description 1
- YRFANZLSFPTENF-UHFFFAOYSA-N propan-2-yl 3-(methylsulfinylmethyl)-2-oxo-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound C1=CN=C2N(C(=O)OC(C)C)C(CS(C)=O)C(=O)NC2=C1 YRFANZLSFPTENF-UHFFFAOYSA-N 0.000 description 1
- BWAUROVQQMZISB-UHFFFAOYSA-N propan-2-yl 3-phenyl-2-sulfanylidene-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound S=C1NC2=CC=CN=C2N(C(=O)OC(C)C)C1C1=CC=CC=C1 BWAUROVQQMZISB-UHFFFAOYSA-N 0.000 description 1
- GMYHCJAQDDAZBW-UHFFFAOYSA-N propan-2-yl 5-methoxy-3-(methylsulfanylmethyl)-2-oxo-1,3-dihydropyrazino[2,3-d]pyridazine-4-carboxylate Chemical compound N1C(=O)C(CSC)N(C(=O)OC(C)C)C2=C1C=NN=C2OC GMYHCJAQDDAZBW-UHFFFAOYSA-N 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003216 pyrazines Chemical class 0.000 description 1
- OUFHXMSGJIYFPW-UHFFFAOYSA-N pyrazino[2,3-c]pyridazine Chemical class N1=NC=CC2=NC=CN=C21 OUFHXMSGJIYFPW-UHFFFAOYSA-N 0.000 description 1
- 150000004892 pyridazines Chemical class 0.000 description 1
- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical class N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- FGEJJBGRIFKJTB-UHFFFAOYSA-N silylsulfanylsilane Chemical class [SiH3]S[SiH3] FGEJJBGRIFKJTB-UHFFFAOYSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- BDIWFCKBPZPBQT-UHFFFAOYSA-N tributyl(tributylstannylsulfanyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)S[Sn](CCCC)(CCCC)CCCC BDIWFCKBPZPBQT-UHFFFAOYSA-N 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- NBTHYJWPOYZDHL-UHFFFAOYSA-N tricyclohexyl(tricyclohexylstannylsulfanyl)stannane Chemical compound C1CCCCC1[Sn](C1CCCCC1)(C1CCCCC1)S[Sn](C1CCCCC1)(C1CCCCC1)C1CCCCC1 NBTHYJWPOYZDHL-UHFFFAOYSA-N 0.000 description 1
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
- NTCQOKPUDSWFJF-UHFFFAOYSA-N triphenyl(triphenylstannylsulfanyl)stannane Chemical compound C=1C=CC=CC=1[Sn](C=1C=CC=CC=1)(C=1C=CC=CC=1)S[Sn](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 NTCQOKPUDSWFJF-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Communicable Diseases (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Plural Heterocyclic Compounds (AREA)
- Radar Systems Or Details Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE4232392 | 1992-09-26 | ||
| DE4232392 | 1992-09-26 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU4755393A AU4755393A (en) | 1994-03-31 |
| AU664643B2 true AU664643B2 (en) | 1995-11-23 |
Family
ID=6468974
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU47553/93A Ceased AU664643B2 (en) | 1992-09-26 | 1993-09-23 | Azaquinoxalines, processes for their preparation and their use |
Country Status (20)
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|---|---|
| US (1) | US5424311A (en, 2012) |
| EP (1) | EP0590428B1 (en, 2012) |
| JP (1) | JPH06211855A (en, 2012) |
| KR (1) | KR940007035A (en, 2012) |
| AT (1) | ATE187724T1 (en, 2012) |
| AU (1) | AU664643B2 (en, 2012) |
| CA (1) | CA2106882C (en, 2012) |
| CZ (1) | CZ9302005A3 (en, 2012) |
| DE (1) | DE59309902D1 (en, 2012) |
| DK (1) | DK0590428T3 (en, 2012) |
| ES (1) | ES2141744T3 (en, 2012) |
| GR (1) | GR3032520T3 (en, 2012) |
| HU (1) | HUT65302A (en, 2012) |
| IL (1) | IL107081A (en, 2012) |
| MX (1) | MX9305894A (en, 2012) |
| NZ (1) | NZ248762A (en, 2012) |
| PH (1) | PH30348A (en, 2012) |
| PT (1) | PT590428E (en, 2012) |
| TW (1) | TW274550B (en, 2012) |
| ZA (1) | ZA937081B (en, 2012) |
Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09510695A (ja) * | 1994-01-03 | 1997-10-28 | エイシア・ファーマシュウティカルズ，インコーポレイテッド | ８−アザ、６−アザ、および６，８−ジアザ−１，４−ジヒドロキノキサリン−２，３−ジオン類およびそのグリシン／ｎｍｄａリセプターに対するアンタゴニストとしての使用 |
| US5801183A (en) * | 1995-01-27 | 1998-09-01 | State Of Oregon, Acting By And Through The Oregon State Board Of Higher Education, Acting For And On Behalf Of The Oregon Health Sciences University And The University Of Oregon | Aza and aza (N-oxy) analogs of glycine/NMDA receptor antagonists |
| US5646130A (en) * | 1995-06-30 | 1997-07-08 | Ocean University Of Oingdao | Low molecular weight sulfated polysaccharides and uses thereof |
| ZA973884B (en) | 1996-05-23 | 1998-11-06 | Du Pont Merck Pharma | Tetrahydropteridines and pyridylpiperazines for treatment of neurological disorders |
| ATE264093T1 (de) | 1998-07-16 | 2004-04-15 | Aaron Tabor | Sojazubereitungen und deren verwendung zur gesundheitsförderung |
| US6930101B1 (en) | 1999-05-17 | 2005-08-16 | The Regents Of The University Of California | Thiazolopyrimidines useful as TNFα inhibitors |
| WO2003079986A2 (en) | 2002-03-18 | 2003-10-02 | Bristol-Myers Squibb Company | Uracil derivatives as inhibitors of tnf-alpha converting enzyme (tace) and matrix metalloproteinases |
| US6861422B2 (en) * | 2003-02-26 | 2005-03-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions |
| DE10323345A1 (de) * | 2003-05-23 | 2004-12-16 | Zentaris Gmbh | Neue Pyridopyrazine und deren Verwendung als Kinase-Inhibitoren |
| ATE411992T1 (de) * | 2003-05-23 | 2008-11-15 | Fterna Zentaris Gmbh | Neue pyridopyrazine und deren verwendung als modulatoren von kinasen |
| MY147767A (en) * | 2004-06-16 | 2013-01-31 | Janssen Pharmaceutica Nv | Novel sulfamate and sulfamide derivatives useful for the treatment of epilepsy and related disorders |
| DE102004029784A1 (de) | 2004-06-21 | 2006-01-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel |
| DE102004033670A1 (de) * | 2004-07-09 | 2006-02-02 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Pyridodihydropyrazinone, Verfahren zu Ihrer Herstellung und Ihre Verwendung als Arzneimittel |
| US20060074088A1 (en) * | 2004-08-14 | 2006-04-06 | Boehringer Ingelheim International Gmbh | Dihydropteridinones for the treatment of cancer diseases |
| US7728134B2 (en) * | 2004-08-14 | 2010-06-01 | Boehringer Ingelheim International Gmbh | Hydrates and polymorphs of 4[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide, process for their manufacture and their use as medicament |
| US20060058311A1 (en) | 2004-08-14 | 2006-03-16 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation |
| US7759485B2 (en) * | 2004-08-14 | 2010-07-20 | Boehringer Ingelheim International Gmbh | Process for the manufacture of dihydropteridinones |
| US20060035903A1 (en) * | 2004-08-14 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Storage stable perfusion solution for dihydropteridinones |
| EP1630163A1 (de) * | 2004-08-25 | 2006-03-01 | Boehringer Ingelheim Pharma GmbH & Co.KG | Dihydropteridinonderivative, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| EP1632493A1 (de) * | 2004-08-25 | 2006-03-08 | Boehringer Ingelheim Pharma GmbH & Co.KG | Dihydropteridinonderivative, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| DE102004058337A1 (de) * | 2004-12-02 | 2006-06-14 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung von annelierten Piperazin-2-on Derivaten |
| US7439358B2 (en) * | 2006-02-08 | 2008-10-21 | Boehringer Ingelheim International Gmbh | Specific salt, anhydrous and crystalline form of a dihydropteridione derivative |
| EA014919B1 (ru) * | 2006-04-21 | 2011-04-29 | Пфайзер Продактс Инк. | ПИРИДИН[3,4-b]ПИРАЗИНОНЫ |
| US7601716B2 (en) * | 2006-05-01 | 2009-10-13 | Cephalon, Inc. | Pyridopyrazines and derivatives thereof as ALK and c-Met inhibitors |
| GB0614471D0 (en) * | 2006-07-20 | 2006-08-30 | Syngenta Ltd | Herbicidal Compounds |
| MX2009004077A (es) * | 2006-10-19 | 2009-05-05 | Signal Pharm Llc | Compuestos de heteroarilo, composiciones de los mismos, y su uso como inhibidores de proteina cinasas. |
| AU2007309468B2 (en) * | 2006-10-19 | 2012-05-17 | Signal Pharmaceuticals, Llc | Heteroaryl compounds, compositions thereof, and use thereof as protein kinase inhibitors |
| WO2008063455A1 (en) * | 2006-11-13 | 2008-05-29 | Hines Richard A | Over-the wire exclusion device and system for delivery |
| EP3098223A1 (en) * | 2007-08-03 | 2016-11-30 | Boehringer Ingelheim International GmbH | Crystalline form of a dihydropteridione derivative |
| US8110578B2 (en) | 2008-10-27 | 2012-02-07 | Signal Pharmaceuticals, Llc | Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway |
| EP3210982A1 (en) | 2008-12-09 | 2017-08-30 | Gilead Sciences, Inc. | Modulators of toll-like receptors |
| CA2750106A1 (en) * | 2009-01-23 | 2010-07-29 | Takeda Pharmaceutical Company Limited | Poly (adp-ribose) polymerase (parp) inhibitors |
| WO2011014681A1 (en) | 2009-07-30 | 2011-02-03 | Takeda Pharmaceutical Company Limited | Poly (ADP-Ribose) Polymerase (PARP) INHIBITORS |
| NZ598384A (en) * | 2009-09-14 | 2014-04-30 | Gilead Sciences Inc | Modulators of toll-like receptors |
| NZ618135A (en) | 2009-10-26 | 2015-05-29 | Signal Pharm Llc | Methods of synthesis and purification of heteroaryl compounds |
| JP6114554B2 (ja) * | 2010-02-03 | 2017-04-12 | シグナル ファーマシューティカルズ，エルエルシー | Ｔｏｒキナーゼ阻害剤に対する感受性についての予測的なバイオマーカーとしてのｌｋｂ１変異の同定 |
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| AU4251885A (en) * | 1984-05-18 | 1985-11-21 | Laboratoires Upsa | New heterocyclic derivatives, the processes for their preparation and drugs in which they are present, which are useful especially as aldose reductase inhibitors |
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| US4077955A (en) * | 1977-02-17 | 1978-03-07 | E. R. Squibb & Sons, Inc. | Amino derivatives of 1,2,3,4-tetrahydro-2-oxopyrido[2,2-b]-pyrazine carboxylic acids and esters |
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- 1993-09-09 TW TW082107380A patent/TW274550B/zh active
- 1993-09-16 AT AT93114934T patent/ATE187724T1/de not_active IP Right Cessation
- 1993-09-16 DE DE59309902T patent/DE59309902D1/de not_active Expired - Fee Related
- 1993-09-16 PT PT93114934T patent/PT590428E/pt unknown
- 1993-09-16 DK DK93114934T patent/DK0590428T3/da active
- 1993-09-16 EP EP93114934A patent/EP0590428B1/de not_active Expired - Lifetime
- 1993-09-16 ES ES93114934T patent/ES2141744T3/es not_active Expired - Lifetime
- 1993-09-23 US US08/125,163 patent/US5424311A/en not_active Expired - Lifetime
- 1993-09-23 IL IL10708193A patent/IL107081A/en not_active IP Right Cessation
- 1993-09-23 AU AU47553/93A patent/AU664643B2/en not_active Ceased
- 1993-09-24 JP JP5237679A patent/JPH06211855A/ja active Pending
- 1993-09-24 ZA ZA937081A patent/ZA937081B/xx unknown
- 1993-09-24 PH PH46948A patent/PH30348A/en unknown
- 1993-09-24 NZ NZ248762A patent/NZ248762A/en unknown
- 1993-09-24 MX MX9305894A patent/MX9305894A/es not_active IP Right Cessation
- 1993-09-24 HU HU9302696A patent/HUT65302A/hu unknown
- 1993-09-24 CA CA002106882A patent/CA2106882C/en not_active Expired - Fee Related
- 1993-09-24 CZ CZ932005A patent/CZ9302005A3/cs unknown
- 1993-09-25 KR KR1019930019733A patent/KR940007035A/ko not_active Withdrawn
-
2000
- 2000-01-31 GR GR20000400216T patent/GR3032520T3/el not_active IP Right Cessation
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| AU4251885A (en) * | 1984-05-18 | 1985-11-21 | Laboratoires Upsa | New heterocyclic derivatives, the processes for their preparation and drugs in which they are present, which are useful especially as aldose reductase inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2106882C (en) | 2007-04-17 |
| KR940007035A (ko) | 1994-04-26 |
| NZ248762A (en) | 1996-01-26 |
| ZA937081B (en) | 1994-04-18 |
| US5424311A (en) | 1995-06-13 |
| JPH06211855A (ja) | 1994-08-02 |
| HU9302696D0 (en) | 1993-12-28 |
| EP0590428A1 (de) | 1994-04-06 |
| AU4755393A (en) | 1994-03-31 |
| ES2141744T3 (es) | 2000-04-01 |
| EP0590428B1 (de) | 1999-12-15 |
| PH30348A (en) | 1997-04-02 |
| HUT65302A (en) | 1994-05-02 |
| CZ9302005A3 (en) | 1994-04-13 |
| DK0590428T3 (da) | 2000-05-22 |
| PT590428E (pt) | 2000-04-28 |
| MX9305894A (es) | 1994-03-31 |
| IL107081A (en) | 1999-07-14 |
| IL107081A0 (en) | 1993-12-28 |
| CA2106882A1 (en) | 1994-03-27 |
| DE59309902D1 (de) | 2000-01-20 |
| GR3032520T3 (en) | 2000-05-31 |
| ATE187724T1 (de) | 2000-01-15 |
| TW274550B (en, 2012) | 1996-04-21 |
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