HUT65302A - Azaquinoxaline- derivatives with antiviral effect and process for the production of these compounds and of pharmaceutical preparatives containing it - Google Patents

Azaquinoxaline- derivatives with antiviral effect and process for the production of these compounds and of pharmaceutical preparatives containing it Download PDF

Info

Publication number: HUT65302A
Authority: HU; Hungary
Prior art keywords: alkyl; alkoxy; hydroxy; amino; chloro
Prior art date: 1992-09-26

Application number

HU9302696A

Other languages

English (en)

Hungarian (hu)

Other versions

HU9302696D0 (en

Inventor

Manfred Roesner

Christoph Meichsner

Uta-Maria Billhardt-Troughton

Rudolf Bender

Original Assignee

Hoechst Ag

Priority date (The priority date 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 date listed.)

1992-09-26

Filing date

1993-09-24

Publication date

1994-05-02

1993-09-24 Application filed by Hoechst Ag filed Critical Hoechst Ag

1993-12-28 Publication of HU9302696D0 publication Critical patent/HU9302696D0/hu

1994-05-02 Publication of HUT65302A publication Critical patent/HUT65302A/hu

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 109
238000000034 method Methods 0.000 title claims description 24
238000004519 manufacturing process Methods 0.000 title description 3
230000000840 anti-viral effect Effects 0.000 title description 2
229910052720 vanadium Inorganic materials 0.000 claims abstract description 46
229910052721 tungsten Inorganic materials 0.000 claims abstract description 43
229910052727 yttrium Inorganic materials 0.000 claims abstract description 43
-1 trifluoromethoxy, hydroxy, mercapto Chemical class 0.000 claims description 303
125000003545 alkoxy group Chemical group 0.000 claims description 120
125000001153 fluoro group Chemical group F* 0.000 claims description 119
125000001309 chloro group Chemical group Cl* 0.000 claims description 100
125000000217 alkyl group Chemical group 0.000 claims description 94
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 92
125000003282 alkyl amino group Chemical group 0.000 claims description 67
125000004414 alkyl thio group Chemical group 0.000 claims description 65
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 65
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 64
125000004423 acyloxy group Chemical group 0.000 claims description 56
229910052739 hydrogen Inorganic materials 0.000 claims description 53
239000001257 hydrogen Substances 0.000 claims description 53
125000004663 dialkyl amino group Chemical group 0.000 claims description 52
125000004043 oxo group Chemical group O=* 0.000 claims description 51
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 45
125000001246 bromo group Chemical group Br* 0.000 claims description 44
238000002360 preparation method Methods 0.000 claims description 44
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 43
125000002346 iodo group Chemical group I* 0.000 claims description 38
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical group [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 36
229910052801 chlorine Inorganic materials 0.000 claims description 35
239000000460 chlorine Substances 0.000 claims description 33
125000000753 cycloalkyl group Chemical group 0.000 claims description 29
229910052731 fluorine Inorganic materials 0.000 claims description 27
239000011737 fluorine Substances 0.000 claims description 27
125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 27
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 26
125000004432 carbon atom Chemical group C* 0.000 claims description 26
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 24
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 23
125000001424 substituent group Chemical group 0.000 claims description 23
125000003710 aryl alkyl group Chemical group 0.000 claims description 21
125000003342 alkenyl group Chemical group 0.000 claims description 20
229910052794 bromium Inorganic materials 0.000 claims description 20
125000001072 heteroaryl group Chemical group 0.000 claims description 20
125000000464 thioxo group Chemical group S=* 0.000 claims description 20
229910052760 oxygen Inorganic materials 0.000 claims description 19
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 18
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 18
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
125000000392 cycloalkenyl group Chemical group 0.000 claims description 17
125000004442 acylamino group Chemical group 0.000 claims description 16
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 16
150000002431 hydrogen Chemical group 0.000 claims description 15
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
239000001301 oxygen Substances 0.000 claims description 13
229910052717 sulfur Inorganic materials 0.000 claims description 13
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
239000000203 mixture Substances 0.000 claims description 12
239000011593 sulfur Chemical group 0.000 claims description 12
125000000304 alkynyl group Chemical group 0.000 claims description 11
125000005018 aryl alkenyl group Chemical group 0.000 claims description 11
125000002252 acyl group Chemical group 0.000 claims description 9
125000003118 aryl group Chemical group 0.000 claims description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 8
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 8
229910052740 iodine Inorganic materials 0.000 claims description 8
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
125000001769 aryl amino group Chemical group 0.000 claims description 7
229910052757 nitrogen Inorganic materials 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
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 7
125000003107 substituted aryl group Chemical group 0.000 claims description 7
125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 7
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 6
125000005110 aryl thio group Chemical group 0.000 claims description 6
125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 5
125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 5
125000005137 alkenylsulfonyl group Chemical group 0.000 claims description 5
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 5
125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 5
125000005015 aryl alkynyl 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
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 5
239000011630 iodine Substances 0.000 claims description 5
ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 claims description 4
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 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
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 claims description 4
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims description 3
125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 3
FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical group CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 claims description 3
BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical group [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 3
125000006323 alkenyl amino group Chemical group 0.000 claims description 3
125000005090 alkenylcarbonyl group Chemical group 0.000 claims description 3
125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 3
125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 3
125000005225 alkynyloxycarbonyl group Chemical group 0.000 claims description 3
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 3
238000009472 formulation Methods 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
150000002829 nitrogen Chemical class 0.000 claims description 3
125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 3
229910052711 selenium Chemical group 0.000 claims description 3
239000011669 selenium Chemical group 0.000 claims description 3
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 3
125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims description 2
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 2
125000003302 alkenyloxy group Chemical group 0.000 claims description 2
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
229950005228 bromoform Drugs 0.000 claims description 2
150000001728 carbonyl compounds Chemical class 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
125000001326 naphthylalkyl group Chemical group 0.000 claims description 2
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 2
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 3
239000000546 pharmaceutical excipient Substances 0.000 claims 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 1
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 1
239000000654 additive Substances 0.000 claims 1
125000005108 alkenylthio group Chemical group 0.000 claims 1
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 1
239000000969 carrier Substances 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
241000700605 Viruses Species 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
238000005160 1H NMR spectroscopy Methods 0.000 description 40
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 38
238000006243 chemical reaction Methods 0.000 description 31
238000002844 melting Methods 0.000 description 31
230000008018 melting Effects 0.000 description 31
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
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 23
229910002027 silica gel Inorganic materials 0.000 description 23
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
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
239000000047 product Substances 0.000 description 14
239000000243 solution Substances 0.000 description 14
239000002904 solvent Substances 0.000 description 12
238000005481 NMR spectroscopy Methods 0.000 description 11
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 11
238000004587 chromatography analysis Methods 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 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
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-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
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
229910052784 alkaline earth metal Inorganic materials 0.000 description 8
125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 8
239000002609 medium Substances 0.000 description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
241000725303 Human immunodeficiency virus Species 0.000 description 7
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 7
229910000564 Raney nickel Inorganic materials 0.000 description 7
238000003556 assay Methods 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 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
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
239000003513 alkali Substances 0.000 description 6
239000002585 base Substances 0.000 description 6
125000000623 heterocyclic group Chemical group 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
239000000126 substance Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
WZCKOKPKQZIGNU-UHFFFAOYSA-N 1h-naphthalen-2-one Chemical compound C1=CC=C2C=CC(=O)CC2=C1 WZCKOKPKQZIGNU-UHFFFAOYSA-N 0.000 description 5
102100034343 Integrase Human genes 0.000 description 5
108010092799 RNA-directed DNA polymerase Proteins 0.000 description 5
150000001298 alcohols Chemical class 0.000 description 5
239000012043 crude product Substances 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000012442 inert solvent Substances 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
238000010626 work up procedure Methods 0.000 description 5
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
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
239000000010 aprotic solvent Substances 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
150000004945 aromatic hydrocarbons Chemical class 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
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000012362 glacial acetic acid Substances 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
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 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
125000006239 protecting group Chemical group 0.000 description 4
150000003230 pyrimidines Chemical class 0.000 description 4
239000007787 solid Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000008096 xylene Substances 0.000 description 4
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
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
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 3
229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
125000001931 aliphatic group Chemical group 0.000 description 3
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
229940024606 amino acid Drugs 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
239000000872 buffer Substances 0.000 description 3
238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
150000002391 heterocyclic compounds Chemical class 0.000 description 3
238000005984 hydrogenation reaction Methods 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 3
150000003195 pteridines Chemical class 0.000 description 3
238000010992 reflux Methods 0.000 description 3
238000002821 scintillation proximity assay Methods 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
235000011150 stannous chloride Nutrition 0.000 description 3
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 3
125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 2
125000000081 (C5-C8) cycloalkenyl group Chemical group 0.000 description 2
QINVNYOGWDNSEP-UHFFFAOYSA-N 1h-naphthalene-2-thione Chemical compound C1=CC=C2C=CC(=S)CC2=C1 QINVNYOGWDNSEP-UHFFFAOYSA-N 0.000 description 2
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 2
HIGOCZJARKJCGG-UHFFFAOYSA-N 3,4-dihydro-1h-pyrido[2,3-b]pyrazin-2-one Chemical compound C1=CC=C2NC(=O)CNC2=N1 HIGOCZJARKJCGG-UHFFFAOYSA-N 0.000 description 2
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 2
CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
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 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical group C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical group N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
239000000427 antigen Substances 0.000 description 2
102000036639 antigens Human genes 0.000 description 2
108091007433 antigens Proteins 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000003638 chemical reducing agent Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
150000004292 cyclic ethers Chemical class 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 2
150000008282 halocarbons Chemical class 0.000 description 2
239000005457 ice water Substances 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical group C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
150000007517 lewis acids Chemical class 0.000 description 2
150000002642 lithium compounds Chemical class 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
229910052987 metal hydride Inorganic materials 0.000 description 2
150000004681 metal hydrides Chemical class 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000012071 phase Substances 0.000 description 2
239000003444 phase transfer catalyst Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
VGNSTKNGRXCJRB-UHFFFAOYSA-N prop-1-en-2-yl 3,6-dimethyl-2-oxo-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound CC1=CC=C2NC(=O)C(C)N(C(=O)OC(C)=C)C2=N1 VGNSTKNGRXCJRB-UHFFFAOYSA-N 0.000 description 2
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 2
GSDPADANYSUNOI-UHFFFAOYSA-N propan-2-yl 5-methoxy-2-(methylsulfanylmethyl)-3-oxo-2,4-dihydropyrazino[2,3-d]pyridazine-1-carboxylate Chemical compound CC(C)OC(=O)N1C(CSC)C(=O)NC2=C1C=NN=C2OC GSDPADANYSUNOI-UHFFFAOYSA-N 0.000 description 2
MKRXCQFWPZANDJ-UHFFFAOYSA-N propan-2-yl 5-methoxy-3-(methylsulfanylmethyl)-2-sulfanylidene-1,3-dihydropyrazino[2,3-d]pyridazine-4-carboxylate Chemical compound N1C(=S)C(CSC)N(C(=O)OC(C)C)C2=C1C=NN=C2OC MKRXCQFWPZANDJ-UHFFFAOYSA-N 0.000 description 2
150000004892 pyridazines Chemical class 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000011550 stock solution Substances 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical group S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
238000005987 sulfurization reaction Methods 0.000 description 2
AZCCYNDIEOBLIV-YFKPBYRVSA-N (3S)-3-methyl-3,4-dihydro-1H-pyrido[3,4-b]pyrazin-2-one Chemical compound N1=CC=C2NC(=O)[C@H](C)NC2=C1 AZCCYNDIEOBLIV-YFKPBYRVSA-N 0.000 description 1
CRVCEKLNTIQYBI-BYPYZUCNSA-N (3s)-6-chloro-3-methyl-3,4-dihydro-1h-pyrido[2,3-b]pyrazin-2-one Chemical compound ClC1=CC=C2NC(=O)[C@H](C)NC2=N1 CRVCEKLNTIQYBI-BYPYZUCNSA-N 0.000 description 1
GJRCWSBXBPZIRG-VIFPVBQESA-N (3s)-6-chloro-3-methyl-4-(pyridin-2-ylmethyl)-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound N1([C@H](C(NC2=CC=C(Cl)N=C21)=O)C)CC1=CC=CC=N1 GJRCWSBXBPZIRG-VIFPVBQESA-N 0.000 description 1
125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 description 1
XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical group [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 description 1
LOYZVRIHVZEDMW-UHFFFAOYSA-N 1-bromo-3-methylbut-2-ene Chemical compound CC(C)=CCBr LOYZVRIHVZEDMW-UHFFFAOYSA-N 0.000 description 1
125000006018 1-methyl-ethenyl group Chemical group 0.000 description 1
XGXKZNXCORZWLV-UHFFFAOYSA-N 1h-pyrido[3,4-b]pyrazin-2-one Chemical compound N1=CC=C2NC(=O)C=NC2=C1 XGXKZNXCORZWLV-UHFFFAOYSA-N 0.000 description 1
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
MJNNGMNZUQSJNV-UHFFFAOYSA-N 2,4-dihydro-1h-pyrido[3,4-b]pyrazin-3-one Chemical compound C1=NC=C2NC(=O)CNC2=C1 MJNNGMNZUQSJNV-UHFFFAOYSA-N 0.000 description 1
MHJDKSLZQBDIPG-UHFFFAOYSA-N 2-(2-oxopyrido[2,3-b]pyrazin-1-yl)acetic acid Chemical compound C1=CN=C2N=CC(=O)N(CC(=O)O)C2=C1 MHJDKSLZQBDIPG-UHFFFAOYSA-N 0.000 description 1
CYBOBNODYVJFNM-UHFFFAOYSA-N 2-amino-2-methylbutanoic acid;hydron;chloride Chemical compound Cl.CCC(C)(N)C(O)=O CYBOBNODYVJFNM-UHFFFAOYSA-N 0.000 description 1
GLKCOBIIZKYKFN-UHFFFAOYSA-N 2-aminopteridine-4,7-diol Chemical class N1=CC(O)=NC2=NC(N)=NC(O)=C21 GLKCOBIIZKYKFN-UHFFFAOYSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
UUOLETYDNTVQDY-UHFFFAOYSA-N 2-chloro-3-nitropyridine Chemical compound [O-][N+](=O)C1=CC=CN=C1Cl UUOLETYDNTVQDY-UHFFFAOYSA-N 0.000 description 1
125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
KDVFRMMRZOCFLS-UHFFFAOYSA-N 2-oxopentanoic acid Chemical compound CCCC(=O)C(O)=O KDVFRMMRZOCFLS-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
ORZSUXQJWMYIFX-UHFFFAOYSA-N 3,6-dimethyl-1h-pyrido[2,3-b]pyrazin-2-one Chemical compound N1C(=O)C(C)=NC2=NC(C)=CC=C21 ORZSUXQJWMYIFX-UHFFFAOYSA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
DHVODZREXYLNGL-UHFFFAOYSA-N 3-methyl-1h-pyrido[3,4-b]pyrazin-2-one Chemical compound N1=CC=C2NC(=O)C(C)=NC2=C1 DHVODZREXYLNGL-UHFFFAOYSA-N 0.000 description 1
WZPZTQIRORXUOQ-UHFFFAOYSA-N 3-methyl-6-(4-methylpiperazin-1-yl)-3,4-dihydro-1h-pyrido[2,3-b]pyrazin-2-one Chemical compound C=1C=C2NC(=O)C(C)NC2=NC=1N1CCN(C)CC1 WZPZTQIRORXUOQ-UHFFFAOYSA-N 0.000 description 1
SEPQTYODOKLVSB-UHFFFAOYSA-N 3-methylbut-2-enal Chemical compound CC(C)=CC=O SEPQTYODOKLVSB-UHFFFAOYSA-N 0.000 description 1
PPAULTVPKLVLII-UHFFFAOYSA-N 4,5-diaminopyrimidine Chemical compound NC1=CN=CN=C1N PPAULTVPKLVLII-UHFFFAOYSA-N 0.000 description 1
KMBOWHJTVQMOEA-UHFFFAOYSA-N 4-acetyl-3-phenyl-1,3-dihydropyrido[2,3-b]pyrazin-2-one Chemical compound O=C1NC2=CC=CN=C2N(C(=O)C)C1C1=CC=CC=C1 KMBOWHJTVQMOEA-UHFFFAOYSA-N 0.000 description 1
LIPODSDLKCMVON-UHFFFAOYSA-N 4-bromopent-2-ene Chemical compound CC=CC(C)Br LIPODSDLKCMVON-UHFFFAOYSA-N 0.000 description 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
DPUUMESTNLIFDE-UHFFFAOYSA-N 4h-pyrido[3,4-b]pyrazin-3-one Chemical compound C1=NC=C2NC(=O)C=NC2=C1 DPUUMESTNLIFDE-UHFFFAOYSA-N 0.000 description 1
NYCKHFXMMWUDRT-UHFFFAOYSA-N 5-propan-2-ylimidazo[1,5-a]quinoxalin-4-one Chemical class O=C1N(C(C)C)C2=CC=CC=C2N2C1=CN=C2 NYCKHFXMMWUDRT-UHFFFAOYSA-N 0.000 description 1
ZUPDDKRJOMELAZ-UHFFFAOYSA-N 5h-pteridin-6-one Chemical compound N1=CN=CC2=NC(O)=CN=C21 ZUPDDKRJOMELAZ-UHFFFAOYSA-N 0.000 description 1
LTHIOQAXEXGEPX-UHFFFAOYSA-N 6,8-dihydro-5h-pteridin-7-one Chemical compound N1=CN=C2NC(=O)CNC2=C1 LTHIOQAXEXGEPX-UHFFFAOYSA-N 0.000 description 1
FBHURYMJNMGWLK-UHFFFAOYSA-N 6-chloro-3-(methylsulfanylmethyl)-3,4-dihydro-1h-pyrido[2,3-b]pyrazin-2-one Chemical compound ClC1=CC=C2NC(=O)C(CSC)NC2=N1 FBHURYMJNMGWLK-UHFFFAOYSA-N 0.000 description 1
OHZBBMULIMLOQY-UHFFFAOYSA-N 6-methoxy-3-(methylsulfanylmethyl)-3,4-dihydro-1h-pyrido[2,3-b]pyrazin-2-one Chemical compound N1C(=O)C(CSC)NC2=NC(OC)=CC=C21 OHZBBMULIMLOQY-UHFFFAOYSA-N 0.000 description 1
AEUGHKKPIVZUBO-UHFFFAOYSA-N 6-methyl-6,8-dihydro-5h-pteridin-7-one Chemical compound N1=CN=C2NC(=O)C(C)NC2=C1 AEUGHKKPIVZUBO-UHFFFAOYSA-N 0.000 description 1
XATOCNYGIWXIQM-UHFFFAOYSA-N 6-methylpyridine-2,3-diamine Chemical compound CC1=CC=C(N)C(N)=N1 XATOCNYGIWXIQM-UHFFFAOYSA-N 0.000 description 1
UGYZVBUANICGLW-UHFFFAOYSA-N 7,8-dihydro-5h-pteridin-6-one Chemical compound C1=NC=C2NC(=O)CNC2=N1 UGYZVBUANICGLW-UHFFFAOYSA-N 0.000 description 1
VLBKSFFDAWLLFB-UHFFFAOYSA-N 7-methyl-7,8-dihydro-5h-pteridin-6-one Chemical compound C1=NC=C2NC(=O)C(C)NC2=N1 VLBKSFFDAWLLFB-UHFFFAOYSA-N 0.000 description 1
DUGJQFDZSSADIC-UHFFFAOYSA-N 8-amino-2-oxo-3,4,4a,5-tetrahydro-1h-pyrido[2,3-b]pyrazine-7-carboxylic acid Chemical class N1C(=O)CNC2NC=C(C(O)=O)C(N)=C21 DUGJQFDZSSADIC-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
RSYKERAQUIKZBX-UHFFFAOYSA-N C1=NC=C2NC(=O)C(CC(=O)OCC)N(C(=O)OC(C)C)C2=C1 Chemical compound C1=NC=C2NC(=O)C(CC(=O)OCC)N(C(=O)OC(C)C)C2=C1 RSYKERAQUIKZBX-UHFFFAOYSA-N 0.000 description 1
NVTQBAMQXTYZTM-UHFFFAOYSA-N C1=NC=C2NC(=O)C(CSC)N(C(=O)OC(C)=C)C2=C1 Chemical compound C1=NC=C2NC(=O)C(CSC)N(C(=O)OC(C)=C)C2=C1 NVTQBAMQXTYZTM-UHFFFAOYSA-N 0.000 description 1
QUNVAKGBBWGQCW-UHFFFAOYSA-N C1=NC=C2NC(=S)C(C)(C)N(C(=O)OC(=C)C)C2=N1 Chemical compound C1=NC=C2NC(=S)C(C)(C)N(C(=O)OC(=C)C)C2=N1 QUNVAKGBBWGQCW-UHFFFAOYSA-N 0.000 description 1
QFYGFUNMXNNZSS-UHFFFAOYSA-N C1=NC=C2NC(=S)C(CSC)N(C(=O)OC(C)=C)C2=C1 Chemical compound C1=NC=C2NC(=S)C(CSC)N(C(=O)OC(C)=C)C2=C1 QFYGFUNMXNNZSS-UHFFFAOYSA-N 0.000 description 1
YMMJYQBKSHGXSJ-UHFFFAOYSA-N C1=NC=C2NC(=S)C(CSC)N(C(=O)OC(C)C)C2=N1 Chemical compound C1=NC=C2NC(=S)C(CSC)N(C(=O)OC(C)C)C2=N1 YMMJYQBKSHGXSJ-UHFFFAOYSA-N 0.000 description 1
WAZCHLYDTYFXFC-UHFFFAOYSA-N ClC1=NC=C2NC(=S)C(CSC)N(C(=O)OC(C)C)C2=N1 Chemical compound ClC1=NC=C2NC(=S)C(CSC)N(C(=O)OC(C)C)C2=N1 WAZCHLYDTYFXFC-UHFFFAOYSA-N 0.000 description 1
102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
229940126062 Compound A Drugs 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
229920001917 Ficoll Polymers 0.000 description 1
102000004300 GABA-A Receptors Human genes 0.000 description 1
108090000839 GABA-A Receptors Proteins 0.000 description 1
108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
102000004457 Granulocyte-Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
108010078851 HIV Reverse Transcriptase Proteins 0.000 description 1
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 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
102000000588 Interleukin-2 Human genes 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
102000015696 Interleukins Human genes 0.000 description 1
108010063738 Interleukins Proteins 0.000 description 1
108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
DYHQILQPXGBZKY-UHFFFAOYSA-N N1=CN=C2NC(=O)C(C)(C)N(C(=O)OC(=C)C)C2=C1 Chemical compound N1=CN=C2NC(=O)C(C)(C)N(C(=O)OC(=C)C)C2=C1 DYHQILQPXGBZKY-UHFFFAOYSA-N 0.000 description 1
FXFKWEQVEIXGHQ-UHFFFAOYSA-N N1=CN=C2NC(=O)C(CSC)N(C(=O)OC(C)C)C2=C1 Chemical compound N1=CN=C2NC(=O)C(CSC)N(C(=O)OC(C)C)C2=C1 FXFKWEQVEIXGHQ-UHFFFAOYSA-N 0.000 description 1
DYQBGPGXYVWGDZ-UHFFFAOYSA-N N1C(=O)C(C)N(C(=O)OC(C)=C)C2=NC(OC)=NC=C21 Chemical compound N1C(=O)C(C)N(C(=O)OC(C)=C)C2=NC(OC)=NC=C21 DYQBGPGXYVWGDZ-UHFFFAOYSA-N 0.000 description 1
YGNFQMGNKFVPNY-UHFFFAOYSA-N N1C(=S)C(CSC)N(C(=O)OC(C)C)C2=NC(OC)=NC=C21 Chemical compound N1C(=S)C(CSC)N(C(=O)OC(C)C)C2=NC(OC)=NC=C21 YGNFQMGNKFVPNY-UHFFFAOYSA-N 0.000 description 1
HFBPCGKGOGDVOH-UHFFFAOYSA-N NC1=NC=C2NC(=O)C(C)N(C(=O)OC(C)=C)C2=N1 Chemical compound NC1=NC=C2NC(=O)C(C)N(C(=O)OC(C)=C)C2=N1 HFBPCGKGOGDVOH-UHFFFAOYSA-N 0.000 description 1
UMHVAASGSPULAV-UHFFFAOYSA-N NC1=NC=C2NC(=S)C(C)N(C(=O)OC(C)=C)C2=N1 Chemical compound NC1=NC=C2NC(=S)C(C)N(C(=O)OC(C)=C)C2=N1 UMHVAASGSPULAV-UHFFFAOYSA-N 0.000 description 1
238000012565 NMR experiment Methods 0.000 description 1
206010029897 Obsessive thoughts Diseases 0.000 description 1
108010047620 Phytohemagglutinins Proteins 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
239000012979 RPMI medium Substances 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
DZGGQYRMTMIMOU-UHFFFAOYSA-N S=C1NC2=CC=CN=C2N(C(=O)OC(C)C)C1C1=C(Cl)C=CC=C1Cl Chemical compound S=C1NC2=CC=CN=C2N(C(=O)OC(C)C)C1C1=C(Cl)C=CC=C1Cl DZGGQYRMTMIMOU-UHFFFAOYSA-N 0.000 description 1
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
210000001744 T-lymphocyte Anatomy 0.000 description 1
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
241001061127 Thione Species 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
238000006359 acetalization reaction Methods 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
239000003288 aldose reductase inhibitor Substances 0.000 description 1
229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 1
229910001854 alkali hydroxide Inorganic materials 0.000 description 1
150000001343 alkyl silanes Chemical class 0.000 description 1
150000008051 alkyl sulfates Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
239000012131 assay buffer Substances 0.000 description 1
239000011324 bead Substances 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
230000002051 biphasic effect Effects 0.000 description 1
RLECCBFNWDXKPK-UHFFFAOYSA-N bis(trimethylsilyl)sulfide Chemical compound C[Si](C)(C)S[Si](C)(C)C RLECCBFNWDXKPK-UHFFFAOYSA-N 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000004657 carbamic acid derivatives Chemical class 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
229910002091 carbon monoxide Inorganic materials 0.000 description 1
238000006555 catalytic reaction Methods 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
229940047120 colony stimulating factors Drugs 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000002131 composite material Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000012228 culture supernatant Substances 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 description 1
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
150000002222 fluorine compounds Chemical class 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000000499 gel Substances 0.000 description 1
125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 description 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical group 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000006459 hydrosilylation reaction Methods 0.000 description 1
229960001438 immunostimulant agent Drugs 0.000 description 1
239000003022 immunostimulating agent Substances 0.000 description 1
230000003308 immunostimulating effect Effects 0.000 description 1
238000011534 incubation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Chemical group CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Chemical group C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
229940047124 interferons Drugs 0.000 description 1
229940047122 interleukins Drugs 0.000 description 1
150000002496 iodine Chemical class 0.000 description 1
XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000006629 isopropoxycarbonylamino group Chemical group 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
229940126601 medicinal product Drugs 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
OMBVLJSHPJLTKD-BYPYZUCNSA-N methyl (2r)-2-amino-3-methylsulfanylpropanoate Chemical compound COC(=O)[C@@H](N)CSC OMBVLJSHPJLTKD-BYPYZUCNSA-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
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
MAQULIULLOBHGK-UHFFFAOYSA-N methyl 2-(methylamino)-2-phenylacetate Chemical compound COC(=O)C(NC)C1=CC=CC=C1 MAQULIULLOBHGK-UHFFFAOYSA-N 0.000 description 1
IXEBRVGOAZDAHN-UHFFFAOYSA-N methyl 2-[(6-chloro-3-nitropyridin-2-yl)amino]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)NC1=NC(Cl)=CC=C1[N+]([O-])=O IXEBRVGOAZDAHN-UHFFFAOYSA-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
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
239000012452 mother liquor Substances 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
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 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
229910052763 palladium Inorganic materials 0.000 description 1
239000000137 peptide hydrolase inhibitor 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
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
REGHGGIABPLKTK-UHFFFAOYSA-N prop-1-en-2-yl 2-amino-7,7-dimethyl-6-oxo-5h-pteridine-8-carboxylate Chemical compound NC1=NC=C2NC(=O)C(C)(C)N(C(=O)OC(=C)C)C2=N1 REGHGGIABPLKTK-UHFFFAOYSA-N 0.000 description 1
UWGYXNGNYVMPQQ-UHFFFAOYSA-N prop-1-en-2-yl 2-methoxy-7,7-dimethyl-6-oxo-5h-pteridine-8-carboxylate Chemical compound N1C(=O)C(C)(C)N(C(=O)OC(C)=C)C2=NC(OC)=NC=C21 UWGYXNGNYVMPQQ-UHFFFAOYSA-N 0.000 description 1
RXGHAJYDTOGFKI-UHFFFAOYSA-N prop-1-en-2-yl 2-methoxy-7,7-dimethyl-6-sulfanylidene-5h-pteridine-8-carboxylate Chemical compound N1C(=S)C(C)(C)N(C(=O)OC(C)=C)C2=NC(OC)=NC=C21 RXGHAJYDTOGFKI-UHFFFAOYSA-N 0.000 description 1
VMGJOBSIJYERNQ-UHFFFAOYSA-N prop-1-en-2-yl 2-methoxy-7-methyl-6-sulfanylidene-5,7-dihydropteridine-8-carboxylate Chemical compound N1C(=S)C(C)N(C(=O)OC(C)=C)C2=NC(OC)=NC=C21 VMGJOBSIJYERNQ-UHFFFAOYSA-N 0.000 description 1
XHRXUENPBFXVJI-UHFFFAOYSA-N prop-1-en-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 XHRXUENPBFXVJI-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
PSWAZBPRPDPDKM-UHFFFAOYSA-N prop-1-en-2-yl 3-(2,6-dichlorophenyl)-2-sulfanylidene-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound S=C1NC2=CC=CN=C2N(C(=O)OC(=C)C)C1C1=C(Cl)C=CC=C1Cl PSWAZBPRPDPDKM-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
LYVPUWOUJAFDRM-UHFFFAOYSA-N prop-1-en-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 LYVPUWOUJAFDRM-UHFFFAOYSA-N 0.000 description 1
OZUCXMLSOGLANX-UHFFFAOYSA-N prop-1-en-2-yl 6,6-dimethyl-7-sulfanylidene-8h-pteridine-5-carboxylate Chemical compound N1=CN=C2NC(=S)C(C)(C)N(C(=O)OC(=C)C)C2=C1 OZUCXMLSOGLANX-UHFFFAOYSA-N 0.000 description 1
DVRHKGNRNFWLOX-UHFFFAOYSA-N prop-1-en-2-yl 6-chloro-2-oxo-3-phenyl-3,4-dihydropyrido[2,3-b]pyrazine-1-carboxylate Chemical compound N1C2=NC(Cl)=CC=C2N(C(=O)OC(=C)C)C(=O)C1C1=CC=CC=C1 DVRHKGNRNFWLOX-UHFFFAOYSA-N 0.000 description 1
WPQIOKJQDDPESV-UHFFFAOYSA-N prop-1-en-2-yl 6-chloro-3,3-dimethyl-2-oxo-1h-pyrido[2,3-b]pyrazine-4-carboxylate Chemical compound ClC1=CC=C2NC(=O)C(C)(C)N(C(=O)OC(=C)C)C2=N1 WPQIOKJQDDPESV-UHFFFAOYSA-N 0.000 description 1
RCPNPUNQQUUWIA-UHFFFAOYSA-N prop-1-en-2-yl 6-chloro-3-(methylsulfanylmethyl)-2-oxo-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound ClC1=CC=C2NC(=O)C(CSC)N(C(=O)OC(C)=C)C2=N1 RCPNPUNQQUUWIA-UHFFFAOYSA-N 0.000 description 1
RBCBOYYADQGDHH-UHFFFAOYSA-N prop-1-en-2-yl 6-chloro-3-(methylsulfanylmethyl)-2-sulfanylidene-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound ClC1=CC=C2NC(=S)C(CSC)N(C(=O)OC(C)=C)C2=N1 RBCBOYYADQGDHH-UHFFFAOYSA-N 0.000 description 1
VVIMYUSXTVXCIZ-UHFFFAOYSA-N prop-1-en-2-yl 6-methoxy-3,3-dimethyl-2-oxo-1h-pyrido[2,3-b]pyrazine-4-carboxylate Chemical compound N1C(=O)C(C)(C)N(C(=O)OC(C)=C)C2=NC(OC)=CC=C21 VVIMYUSXTVXCIZ-UHFFFAOYSA-N 0.000 description 1
KJQYDTFLHKSJSP-UHFFFAOYSA-N prop-1-en-2-yl 6-methyl-7-oxo-6,8-dihydropteridine-5-carboxylate Chemical compound N1=CN=C2NC(=O)C(C)N(C(=O)OC(C)=C)C2=C1 KJQYDTFLHKSJSP-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
POKFIULVZNWRNS-UHFFFAOYSA-N prop-1-en-2-yl 7,7-dimethyl-6-oxo-5h-pteridine-8-carboxylate Chemical compound C1=NC=C2NC(=O)C(C)(C)N(C(=O)OC(=C)C)C2=N1 POKFIULVZNWRNS-UHFFFAOYSA-N 0.000 description 1
GZMFFSVZQYQAHG-UHFFFAOYSA-N prop-1-en-2-yl 7-methyl-6-oxo-5,7-dihydropteridine-8-carboxylate Chemical compound C1=NC=C2NC(=O)C(C)N(C(=O)OC(C)=C)C2=N1 GZMFFSVZQYQAHG-UHFFFAOYSA-N 0.000 description 1
AMMGCGVWJMRTQI-UHFFFAOYSA-N prop-1-en-2-yl carbonochloridate Chemical compound CC(=C)OC(Cl)=O AMMGCGVWJMRTQI-UHFFFAOYSA-N 0.000 description 1
YODXTVVGNOHXOK-UHFFFAOYSA-N prop-1-enyl carbonochloridate Chemical compound CC=COC(Cl)=O YODXTVVGNOHXOK-UHFFFAOYSA-N 0.000 description 1
RCMCQWIUWWSUAN-UHFFFAOYSA-N propan-2-yl 2-(methylsulfanylmethyl)-3-sulfanylidene-2,4-dihydropyrido[3,4-b]pyrazine-1-carboxylate Chemical compound C1=NC=C2NC(=S)C(CSC)N(C(=O)OC(C)C)C2=C1 RCMCQWIUWWSUAN-UHFFFAOYSA-N 0.000 description 1
YFPJRSOEWKGHHF-UHFFFAOYSA-N propan-2-yl 2-amino-7-(methylsulfanylmethyl)-6-oxo-5,7-dihydropteridine-8-carboxylate Chemical compound NC1=NC=C2NC(=O)C(CSC)N(C(=O)OC(C)C)C2=N1 YFPJRSOEWKGHHF-UHFFFAOYSA-N 0.000 description 1
DPDYLFNGRPCXCA-UHFFFAOYSA-N propan-2-yl 2-amino-7-(methylsulfanylmethyl)-6-sulfanylidene-5,7-dihydropteridine-8-carboxylate Chemical compound NC1=NC=C2NC(=S)C(CSC)N(C(=O)OC(C)C)C2=N1 DPDYLFNGRPCXCA-UHFFFAOYSA-N 0.000 description 1
FCVLVYOWCMCFHI-UHFFFAOYSA-N propan-2-yl 2-chloro-7-(methylsulfanylmethyl)-6-oxo-5,7-dihydropteridine-8-carboxylate Chemical compound ClC1=NC=C2NC(=O)C(CSC)N(C(=O)OC(C)C)C2=N1 FCVLVYOWCMCFHI-UHFFFAOYSA-N 0.000 description 1
FLXOKBBFVLQVQY-UHFFFAOYSA-N propan-2-yl 2-methoxy-7-(methylsulfanylmethyl)-6-oxo-5,7-dihydropteridine-8-carboxylate Chemical compound N1C(=O)C(CSC)N(C(=O)OC(C)C)C2=NC(OC)=NC=C21 FLXOKBBFVLQVQY-UHFFFAOYSA-N 0.000 description 1
HHIUFBCMNRGIKO-UHFFFAOYSA-N propan-2-yl 3-(2-ethoxy-2-oxoethyl)-2-oxo-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound C1=CC=C2NC(=O)C(CC(=O)OCC)N(C(=O)OC(C)C)C2=N1 HHIUFBCMNRGIKO-UHFFFAOYSA-N 0.000 description 1
RUDOEPZHGRAHLZ-UHFFFAOYSA-N propan-2-yl 3-(methylsulfanylmethyl)-2-oxo-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound C1=CC=C2NC(=O)C(CSC)N(C(=O)OC(C)C)C2=N1 RUDOEPZHGRAHLZ-UHFFFAOYSA-N 0.000 description 1
USJPVYMJCTYNTK-UHFFFAOYSA-N propan-2-yl 5-chloro-2-(methylsulfanylmethyl)-3-oxo-2,4-dihydropyrazino[2,3-d]pyridazine-1-carboxylate Chemical compound N1=NC(Cl)=C2NC(=O)C(CSC)N(C(=O)OC(C)C)C2=C1 USJPVYMJCTYNTK-UHFFFAOYSA-N 0.000 description 1
NOJCAIIFAQUIKS-UHFFFAOYSA-N propan-2-yl 5-chloro-2-(methylsulfanylmethyl)-3-sulfanylidene-2,4-dihydropyrazino[2,3-d]pyridazine-1-carboxylate Chemical compound N1=NC(Cl)=C2NC(=S)C(CSC)N(C(=O)OC(C)C)C2=C1 NOJCAIIFAQUIKS-UHFFFAOYSA-N 0.000 description 1
LDPWSXQHVKNXLZ-UHFFFAOYSA-N propan-2-yl 5-methoxy-2-(methylsulfanylmethyl)-3-sulfanylidene-2,4-dihydropyrazino[2,3-d]pyridazine-1-carboxylate Chemical compound CC(C)OC(=O)N1C(CSC)C(=S)NC2=C1C=NN=C2OC LDPWSXQHVKNXLZ-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
HMWPVNOXKHFNCK-UHFFFAOYSA-N propan-2-yl 6-chloro-3-(methylsulfanylmethyl)-2-oxo-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound ClC1=CC=C2NC(=O)C(CSC)N(C(=O)OC(C)C)C2=N1 HMWPVNOXKHFNCK-UHFFFAOYSA-N 0.000 description 1
HMGCJULSHBUQJJ-UHFFFAOYSA-N propan-2-yl 6-chloro-3-(methylsulfanylmethyl)-2-sulfanylidene-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound ClC1=CC=C2NC(=S)C(CSC)N(C(=O)OC(C)C)C2=N1 HMGCJULSHBUQJJ-UHFFFAOYSA-N 0.000 description 1
WNLFRQFWQBREPR-UHFFFAOYSA-N propan-2-yl 6-methoxy-3-(methylsulfanylmethyl)-2-oxo-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound N1C(=O)C(CSC)N(C(=O)OC(C)C)C2=NC(OC)=CC=C21 WNLFRQFWQBREPR-UHFFFAOYSA-N 0.000 description 1
KDXPODRGWFEAQO-UHFFFAOYSA-N propan-2-yl 6-methoxy-3-(methylsulfanylmethyl)-2-sulfanylidene-1,3-dihydropyrido[2,3-b]pyrazine-4-carboxylate Chemical compound N1C(=S)C(CSC)N(C(=O)OC(C)C)C2=NC(OC)=CC=C21 KDXPODRGWFEAQO-UHFFFAOYSA-N 0.000 description 1
KHPKSSZUBKYZTO-UHFFFAOYSA-N propan-2-yl 6-methyl-7-sulfanylidene-6,8-dihydropteridine-5-carboxylate Chemical compound C1=NC=C2N(C(=O)OC(C)C)C(C)C(=S)NC2=N1 KHPKSSZUBKYZTO-UHFFFAOYSA-N 0.000 description 1
NOWBJNCZDZHCSF-UHFFFAOYSA-N propan-2-yl 7-(methylsulfanylmethyl)-6-oxo-5,7-dihydropteridine-8-carboxylate Chemical compound C1=NC=C2NC(=O)C(CSC)N(C(=O)OC(C)C)C2=N1 NOWBJNCZDZHCSF-UHFFFAOYSA-N 0.000 description 1
PQFITNDZYJXOFI-UHFFFAOYSA-N propan-2-yl 7-methyl-6-sulfanylidene-5,7-dihydropteridine-8-carboxylate Chemical compound N1=CN=C2N(C(=O)OC(C)C)C(C)C(=S)NC2=C1 PQFITNDZYJXOFI-UHFFFAOYSA-N 0.000 description 1
YCSWRJRYPVDVEZ-UHFFFAOYSA-N propan-2-yl n-[3-methyl-4-(2-methylpropanoyl)-2-oxo-1,3-dihydropyrido[2,3-b]pyrazin-6-yl]-n-propylcarbamate Chemical compound N1C(=O)C(C)N(C(=O)C(C)C)C2=NC(N(C(=O)OC(C)C)CCC)=CC=C21 YCSWRJRYPVDVEZ-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
YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical class N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000002976 reverse transcriptase assay Methods 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 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
239000007858 starting material Substances 0.000 description 1
125000005504 styryl group Chemical group 0.000 description 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
239000006228 supernatant Substances 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
125000003396 thiol group Chemical class [H]S* 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 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
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 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
230000003612 virological effect Effects 0.000 description 1
VURKRJGMSKJIQX-UHFFFAOYSA-N xanthopterin Chemical class N1C(=O)C=NC2=C1C(=O)N=C(N)N2 VURKRJGMSKJIQX-UHFFFAOYSA-N 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 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)

HU9302696A 1992-09-26 1993-09-24 Azaquinoxaline- derivatives with antiviral effect and process for the production of these compounds and of pharmaceutical preparatives containing it HUT65302A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE4232392		1992-09-26

Publications (2)

Publication Number	Publication Date
HU9302696D0 HU9302696D0 (en)	1993-12-28
HUT65302A true HUT65302A (en)	1994-05-02

Family

ID=6468974

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
HU9302696A HUT65302A (en)	1992-09-26	1993-09-24	Azaquinoxaline- derivatives with antiviral effect and process for the production of these compounds and of pharmaceutical preparatives containing it

Country Status (20)

Country	Link
US (1)	US5424311A (2)
EP (1)	EP0590428B1 (2)
JP (1)	JPH06211855A (2)
KR (1)	KR940007035A (2)
AT (1)	ATE187724T1 (2)
AU (1)	AU664643B2 (2)
CA (1)	CA2106882C (2)
CZ (1)	CZ9302005A3 (2)
DE (1)	DE59309902D1 (2)
DK (1)	DK0590428T3 (2)
ES (1)	ES2141744T3 (2)
GR (1)	GR3032520T3 (2)
HU (1)	HUT65302A (2)
IL (1)	IL107081A (2)
MX (1)	MX9305894A (2)
NZ (1)	NZ248762A (2)
PH (1)	PH30348A (2)
PT (1)	PT590428E (2)
TW (1)	TW274550B (2)
ZA (1)	ZA937081B (2)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5620978A (en) *	1994-01-03	1997-04-15	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, Eugene Oregon	8-aza, 6-aza and 6,8-diaza-1,4-dihydroquinoxaline-2,3-diones and the use thereof as antagonists for the glycine/NMDA receptor
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
AU2003220401A1 (en)	2002-03-18	2003-10-08	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
AU2004240747B2 (en) *	2003-05-23	2008-01-03	Zentaris Gmbh	Novel pyridopyrazines and use thereof as kinase modulators
DE10323345A1 (de) *	2003-05-23	2004-12-16	Zentaris Gmbh	Neue Pyridopyrazine und deren Verwendung als Kinase-Inhibitoren
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
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
US7759485B2 (en) *	2004-08-14	2010-07-20	Boehringer Ingelheim International Gmbh	Process for the manufacture of dihydropteridinones
US20060074088A1 (en) *	2004-08-14	2006-04-06	Boehringer Ingelheim International Gmbh	Dihydropteridinones for the treatment of cancer diseases
US20060035903A1 (en) *	2004-08-14	2006-02-16	Boehringer Ingelheim International Gmbh	Storage stable perfusion solution for dihydropteridinones
US20060058311A1 (en)	2004-08-14	2006-03-16	Boehringer Ingelheim International Gmbh	Combinations for the treatment of diseases involving cell proliferation
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
RS20080484A (sr) *	2006-04-21	2009-07-15	Pfizer Products Inc.,	PIRIDIN[3,4-b] PIRAZINONI
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
ATE543819T1 (de) *	2006-10-19	2012-02-15	Signal Pharm Llc	Heteroarylverbindungen, zusammensetzungen daraus und behandlungsverfahren damit
US7968556B2 (en) *	2006-10-19	2011-06-28	Signal Pharmaceuticals, Llc	Heteroaryl compounds, compositions thereof, and methods of treatment therewith
WO2008063455A1 (en) *	2006-11-13	2008-05-29	Hines Richard A	Over-the wire exclusion device and system for delivery
EP2185559A1 (en) *	2007-08-03	2010-05-19	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
ES2467108T3 (es)	2008-12-09	2014-06-11	Gilead Sciences, Inc.	Moduladores de receptores tipo toll
KR101779137B1 (ko) *	2009-01-23	2017-09-18	다케다 야쿠힌 고교 가부시키가이샤	폴리(ａｄｐ-리보스)폴리머라제(ｐａｒｐ) 억제제
EP2459561A1 (en)	2009-07-30	2012-06-06	Takeda Pharmaceutical Company Limited	Poly (adp-ribose) polymerase (parp) inhibitors
NO2477987T3 (2) *	2009-09-14	2018-06-09
MY177695A (en)	2009-10-26	2020-09-23	Signal Pharm Llc	Methods of synthesis and purification of heteroaryl compounds
EP2531194B1 (en) *	2010-02-03	2018-04-18	Signal Pharmaceuticals, LLC	Identification of lkb1 mutation as a predictive biomarker for sensitivity to tor kinase inhibitors
US8546566B2 (en)	2010-10-12	2013-10-01	Boehringer Ingelheim International Gmbh	Process for manufacturing dihydropteridinones and intermediates thereof
US9358233B2 (en)	2010-11-29	2016-06-07	Boehringer Ingelheim International Gmbh	Method for treating acute myeloid leukemia
US9370535B2 (en)	2011-05-17	2016-06-21	Boehringer Ingelheim International Gmbh	Method for treatment of advanced solid tumors
KR101978537B1 (ko)	2011-10-19	2019-05-14	시그날 파마소티칼 엘엘씨	Tor 키나제 억제제를 사용한 암의 치료
US9351974B2 (en)	2011-11-10	2016-05-31	OSI Pharmaceuticals, LLC	Substituted pteridinones for the treatment of cancer
JP6076370B2 (ja)	2011-12-02	2017-02-08	シグナルファーマシューティカルズ，エルエルシー	７−（６−（２−ヒドロキシプロパン−２−イル）ピリジン−３−イル）−１−（（トランス）−４−メトキシシクロヘキシル）−３，４−ジヒドロピラジノ［２，３−ｂ］ピラジン−２（１Ｈ）−オンの薬剤組成物、その固体形態、およびその使用方法
TWI615143B (zh)	2012-02-24	2018-02-21	標誌製藥公司	使用ｔｏｒ激酶抑制劑組合療法以治療癌症之方法
AU2013203714B2 (en)	2012-10-18	2015-12-03	Signal Pharmaceuticals, Llc	Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity
EP2945636B1 (en)	2013-01-16	2017-06-28	Signal Pharmaceuticals, LLC	Substituted pyrrolopyrimidine compounds, compositions thereof, and methods of treatment therewith
BR112015026297B1 (pt)	2013-04-17	2022-08-23	Signal Pharmaceuticals, Llc	Uso de um inibidor da quinase tor e quinazolinona 5-substituída, composição farmacêutica que os compreende, e kit
TW201527300A (zh)	2013-04-17	2015-07-16	Signal Pharm Llc	關於１－乙基－７－（２－甲基－６－（１Ｈ－１，２，４－三唑－３－基）吡啶－３－基）－３，４－二氫吡并［２，３－ｂ］吡－２（１Ｈ）－酮之醫藥調配物、方法、固態型式及使用方法
US9937169B2 (en)	2013-04-17	2018-04-10	Signal Pharmaceuticals, Llc	Methods for treating cancer using dihydropyrazino-pyrazine compound combination therapy
TW201521725A (zh)	2013-04-17	2015-06-16	Signal Pharm Llc	使用ｔｏｒ激酶抑制劑組合療法以治療癌症之方法
AU2014254052B2 (en)	2013-04-17	2019-06-06	Signal Pharmaceuticals, Llc	Treatment of cancer with dihydropyrazino-pyrazines
BR112015026292B1 (pt)	2013-04-17	2022-04-12	Signal Pharmaceuticals, Llc	Uso de 1-etil-7-(2-metil-6-(1h-1,2,4-triazol-3-il)piridin-3-il)-3,4-dihidropirazino [2,3-b]pirazin-2(1h)- ona e métodos in vitro
US9782427B2 (en)	2013-04-17	2017-10-10	Signal Pharmaceuticals, Llc	Methods for treating cancer using TOR kinase inhibitor combination therapy
EP3003313A1 (en)	2013-05-29	2016-04-13	Signal Pharmaceuticals, LLC	Pharmaceutical compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, a solid form thereof and methods of their use
US20150031699A1 (en)	2013-07-26	2015-01-29	Boehringer Ingelheim International Gmbh	Treatment of myelodysplastic syndrome
NZ714742A (en)	2014-04-16	2017-04-28	Signal Pharm Llc	Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use
EP3131552B1 (en)	2014-04-16	2020-07-15	Signal Pharmaceuticals, LLC	Methods for treating cancer using tor kinase inhibitor combination therapy
US9512129B2 (en)	2014-04-16	2016-12-06	Signal Pharmaceuticals, Llc	Solid forms comprising 1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one and a coformer
US9718824B2 (en)	2014-04-16	2017-08-01	Signal Pharmaceuticals, Llc	Solid forms comprising 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one, and a coformer, compositions and methods of use thereof
PT3166607T (pt)	2014-07-11	2022-12-07	Gilead Sciences Inc	Moduladores de receptores de tipo toll para o tratamento do vih
EA201790189A1 (ru)	2014-07-14	2017-11-30	СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи	Способы лечения злокачественного новообразования с использованием замещенных пирролопиримидиновых соединений, композиции на их основе
NZ629796A (en)	2014-07-14	2015-12-24	Signal Pharm Llc	Amorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use
BR112017005100A2 (pt)	2014-09-16	2017-12-05	Gilead Sciences Inc	métodos de preparação de moduladores de receptores do tipo toll
CA2960436C (en)	2014-09-16	2021-01-05	Gilead Sciences, Inc.	Solid forms of a toll-like receptor modulator
US9867831B2 (en)	2014-10-01	2018-01-16	Boehringer Ingelheim International Gmbh	Combination treatment of acute myeloid leukemia and myelodysplastic syndrome
EP3641772B1 (en)	2017-06-22	2023-08-02	Celgene Corporation	Treatment of hepatocellular carcinoma characterized by hepatitis b virus infection
KR102272284B1 (ko) *	2020-01-13	2021-07-02	금오공과대학교 산학협력단	정밀 압력제어가 가능한 다단 스프링 압력제어밸브
TW202523312A (zh) *	2023-10-16	2025-06-16	美商克洛諾斯生技有限公司	離胺酸乙醯基轉移酶抑制劑

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
GR72941B (2) *	1978-10-20	1984-01-16	Lilly Co Eli
IE58312B1 (en) *	1984-05-18	1993-09-08	Union Pharma Scient Appl	Heterocyclic derivatives, processes for their preparation and drugs in which they are present, which are useful especially as aldose reductase inhibitors
JPH0276860A (ja) *	1987-10-05	1990-03-16	Toyo Jozo Co Ltd	６−置換アルコキシ−２−オキソ−１，２−ジヒドロキノキサリン誘導体
DK160876C (da) *	1987-12-08	1991-10-14	Novo Nordisk As	Imidazoquinoxalinforbindelser, fremgangsmaade til deres fremstilling, anvendelse af forbindelserne og farmaceutiske praeparater, hvori forbindelserne indgaar
PT509398E (pt) *	1991-04-15	2002-02-28	Aventis Pharma Gmbh	Quinoxalinas processo para a sua preparacao e sua utilizacao

1993
- 1993-09-09 TW TW082107380A patent/TW274550B/zh active
- 1993-09-16 PT PT93114934T patent/PT590428E/pt unknown
- 1993-09-16 DK DK93114934T patent/DK0590428T3/da active
- 1993-09-16 AT AT93114934T patent/ATE187724T1/de not_active IP Right Cessation
- 1993-09-16 ES ES93114934T patent/ES2141744T3/es not_active Expired - Lifetime
- 1993-09-16 DE DE59309902T patent/DE59309902D1/de not_active Expired - Fee Related
- 1993-09-16 EP EP93114934A patent/EP0590428B1/de not_active Expired - Lifetime
- 1993-09-23 AU AU47553/93A patent/AU664643B2/en not_active Ceased
- 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
- 1993-09-24 NZ NZ248762A patent/NZ248762A/en unknown
- 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 HU HU9302696A patent/HUT65302A/hu unknown
- 1993-09-24 CZ CZ932005A patent/CZ9302005A3/cs unknown
- 1993-09-24 CA CA002106882A patent/CA2106882C/en not_active Expired - Fee Related
- 1993-09-24 MX MX9305894A patent/MX9305894A/es not_active IP Right Cessation
- 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

Also Published As

Publication number	Publication date
DE59309902D1 (de)	2000-01-20
EP0590428A1 (de)	1994-04-06
DK0590428T3 (da)	2000-05-22
PT590428E (pt)	2000-04-28
CA2106882C (en)	2007-04-17
NZ248762A (en)	1996-01-26
IL107081A (en)	1999-07-14
AU664643B2 (en)	1995-11-23
HU9302696D0 (en)	1993-12-28
MX9305894A (es)	1994-03-31
US5424311A (en)	1995-06-13
EP0590428B1 (de)	1999-12-15
CZ9302005A3 (en)	1994-04-13
ES2141744T3 (es)	2000-04-01
ZA937081B (en)	1994-04-18
AU4755393A (en)	1994-03-31
IL107081A0 (en)	1993-12-28
JPH06211855A (ja)	1994-08-02
GR3032520T3 (en)	2000-05-31
KR940007035A (ko)	1994-04-26
TW274550B (2)	1996-04-21
PH30348A (en)	1997-04-02
CA2106882A1 (en)	1994-03-27
ATE187724T1 (de)	2000-01-15

Legal Events

Date	Code	Title	Description
1996-12-30	DFA9	Temporary protection cancelled due to abandonment

Publication	Publication Date	Title
HUT65302A (en)	1994-05-02	Azaquinoxaline- derivatives with antiviral effect and process for the production of these compounds and of pharmaceutical preparatives containing it
EP2415767B1 (en)	2014-09-03	Poly (ADP-ribose) Polymerase (PARP) Inhibitors
EP1343780B1 (en)	2006-09-20	Piperazine derivatives for treatment of bacterial infections
US20070179165A1 (en)	2007-08-02	Cyclic compounds
JPH11504922A (ja)	1999-05-11	蛋白チロシンキナーゼ媒介細胞増殖を抑制するためのピリド［２，３−ｄ］ピリミジン類
AU1081700A (en)	2000-05-29	Pyrazolopyrimidinone derivatives for the treatment of impotence
HU193754B (en)	1987-11-30	Process for preparing pyrrolo-benzimidazoles
HU207068B (en)	1993-03-01	Process for producing thiadiazone derivatives and pharmaceutical compositions comprising same
US20030187257A1 (en)	2003-10-02	Triazolo[4,3-a]pyrido[2,3-d]pyrimidin-5-one derivatives
IE921187A1 (en)	1992-10-21	Quinoxalines, processes for their preparation, and their use
NZ539598A (en)	2006-11-30	Pyridopyrimidinone compounds, method for production thereof and medicaments comprising the same
US6369057B1 (en)	2002-04-09	Quinoxalines, processes for their preparation and their use
US20020006380A1 (en)	2002-01-17	Pyrrole derivatives, their preparation and pharmaceutical compositions containing them
US6114349A (en)	2000-09-05	Substituted quinoline derivatives with antiviral action
NZ280258A (en)	1997-09-22	Quinoxaline derivatives; preparative method and medicaments
JP3605123B2 (ja)	2004-12-22	４−イミノキノリン、その製法およびそれを含有する抗ウイルス剤
JPH0859621A (ja)	1996-03-05	置換キノリン誘導体、それらの製造方法およびそれらの使用
EP0511792A2 (en)	1992-11-04	Pyridoprimidine derivatives as antineoplastic agents
CS220343B2 (en)	1983-03-25	Method of producing new imidazoquinazoline derivatives
A Ghoneim et al.	2015	Synthesis of some new chromeno [2, 3-b] pyridine and [1, 2, 4] triazolo [1, 5-a] quinoline nucleoside analogues with expected biological activity
US6525063B2 (en)	2003-02-25	Antitumour 1,5-diazaanthraquinones
US6949652B2 (en)	2005-09-27	Crystalline forms of 3-isopropyl-6-[4-(2,5-difluoro-phenyl)-oxazol-5-yl]-[1,2,4]triazolo-[4,3-A]pyridine
US4451650A (en)	1984-05-29	Pyrido[4,3-b][1,4]oxazines and pyrido[4,3-b][1,4]thiazines
WO1992012979A1 (en)	1992-08-06	2,4-DIOXO-PYRIDO [2,3-d]PYRIMIDINE-3-ACETIC ACIDS AND ESTERS AND SALTS THEREOF
EP1806348A2 (en)	2007-07-11	Pyrido (2,3-D)Pyrimidines as inhibitors of cellular proliferation