SK283467B6 - Chinoxalíndióny, spôsob a medziprodukty na ich výrobu, ich použitie a farmaceutické kompozície na ich báze - Google Patents

Chinoxalíndióny, spôsob a medziprodukty na ich výrobu, ich použitie a farmaceutické kompozície na ich báze Download PDF

Info

Publication number: SK283467B6
Authority: SK; Slovakia
Prior art keywords: triazol; methyl; pyridin; alkyl; methoxymethyl
Prior art date: 1996-03-09

Application number

SK1214-98A

Other languages

English (en)

Slovak (sk)

Other versions

SK121498A3 (en

Inventor

David John Bull

Christopher Lee Carr

Michael Jonathan Fray

Elisabeth Colette Louise Gautier

Charles Eric Mowbray

Alan Stobie

Original Assignee

Pfizer Research And Development Company, N. V./S. A.

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.)

1996-03-09

Filing date

1997-02-27

Publication date

2003-08-05

1997-02-27 Application filed by Pfizer Research And Development Company, N. V./S. A. filed Critical Pfizer Research And Development Company, N. V./S. A.

2000-10-09 Publication of SK121498A3 publication Critical patent/SK121498A3/sk

2003-08-05 Publication of SK283467B6 publication Critical patent/SK283467B6/sk

Links

238000000034 method Methods 0.000 title claims abstract description 123
SEPKUNXLGWMPHL-UHFFFAOYSA-N quinoxaline-2,3-dione Chemical class C1=CC=CC2=NC(=O)C(=O)N=C21 SEPKUNXLGWMPHL-UHFFFAOYSA-N 0.000 title claims abstract description 21
230000008569 process Effects 0.000 title claims abstract description 10
238000004519 manufacturing process Methods 0.000 title claims abstract description 6
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
239000000543 intermediate Substances 0.000 title abstract description 12
150000001875 compounds Chemical class 0.000 claims abstract description 142
150000003839 salts Chemical class 0.000 claims abstract description 54
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 41
125000001424 substituent group Chemical group 0.000 claims abstract description 26
229910052799 carbon Inorganic materials 0.000 claims abstract description 25
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 18
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 14
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 13
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 13
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 9
125000001153 fluoro group Chemical group F* 0.000 claims abstract description 6
125000001246 bromo group Chemical group Br* 0.000 claims abstract description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
125000005843 halogen group Chemical group 0.000 claims abstract description 3
-1 C 1 -C 4 alkoxy Chemical group 0.000 claims description 351
239000000460 chlorine Substances 0.000 claims description 108
239000000203 mixture Substances 0.000 claims description 84
229910052801 chlorine Inorganic materials 0.000 claims description 40
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 39
125000003118 aryl group Chemical group 0.000 claims description 35
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 33
125000003545 alkoxy group Chemical group 0.000 claims description 22
229910052736 halogen Inorganic materials 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
125000005605 benzo group Chemical group 0.000 claims description 15
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
125000004076 pyridyl group Chemical group 0.000 claims description 14
125000000217 alkyl group Chemical group 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 13
125000000714 pyrimidinyl group Chemical group 0.000 claims description 13
125000003373 pyrazinyl group Chemical group 0.000 claims description 12
125000002098 pyridazinyl group Chemical group 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
125000004104 aryloxy group Chemical group 0.000 claims description 10
125000000753 cycloalkyl group Chemical group 0.000 claims description 10
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
201000010099 disease Diseases 0.000 claims description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
125000003831 tetrazolyl group Chemical group 0.000 claims description 9
125000001425 triazolyl group Chemical group 0.000 claims description 9
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
125000002883 imidazolyl group Chemical group 0.000 claims description 8
125000001786 isothiazolyl group Chemical group 0.000 claims description 8
125000001715 oxadiazolyl group Chemical group 0.000 claims description 8
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 8
125000000168 pyrrolyl group Chemical group 0.000 claims description 8
125000001113 thiadiazolyl group Chemical group 0.000 claims description 8
125000000335 thiazolyl group Chemical group 0.000 claims description 8
125000001544 thienyl group Chemical group 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
125000001188 haloalkyl group Chemical group 0.000 claims description 7
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
125000003226 pyrazolyl group Chemical group 0.000 claims description 7
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 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
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 6
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims description 6
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 6
125000000842 isoxazolyl group Chemical group 0.000 claims description 6
125000002971 oxazolyl group Chemical group 0.000 claims description 6
125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 6
125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 claims description 5
208000012902 Nervous system disease Diseases 0.000 claims description 5
230000001154 acute effect Effects 0.000 claims description 5
230000001684 chronic effect Effects 0.000 claims description 5
125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 4
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
241000124008 Mammalia Species 0.000 claims description 4
229940099433 NMDA receptor antagonist Drugs 0.000 claims description 4
230000002378 acidificating effect Effects 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
125000002541 furyl group Chemical group 0.000 claims description 4
150000002431 hydrogen Chemical class 0.000 claims description 4
208000028867 ischemia Diseases 0.000 claims description 4
239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 claims description 4
230000000626 neurodegenerative effect Effects 0.000 claims description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 3
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 3
206010019196 Head injury Diseases 0.000 claims description 3
208000006011 Stroke Diseases 0.000 claims description 3
208000032109 Transient ischaemic attack Diseases 0.000 claims description 3
238000005903 acid hydrolysis reaction Methods 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
230000000694 effects Effects 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
125000004550 quinolin-6-yl group Chemical group N1=CC=CC2=CC(=CC=C12)* 0.000 claims description 3
201000010875 transient cerebral ischemia Diseases 0.000 claims description 3
230000000472 traumatic effect Effects 0.000 claims description 3
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
MWZDIEIXRBWPLG-UHFFFAOYSA-N 1-methyl-1,2,4-triazole Chemical compound CN1C=NC=N1 MWZDIEIXRBWPLG-UHFFFAOYSA-N 0.000 claims 1
SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 claims 1
125000005805 dimethoxy phenyl group Chemical group 0.000 claims 1
125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
230000006698 induction Effects 0.000 claims 1
125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 228
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 222
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 174
239000007787 solid Substances 0.000 description 105
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 78
238000005481 NMR spectroscopy Methods 0.000 description 67
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 63
XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 63
239000000243 solution Substances 0.000 description 62
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 60
239000002253 acid Substances 0.000 description 58
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
238000005406 washing Methods 0.000 description 39
239000000741 silica gel Substances 0.000 description 37
229910002027 silica gel Inorganic materials 0.000 description 37
238000003818 flash chromatography Methods 0.000 description 36
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 31
238000010828 elution Methods 0.000 description 31
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
239000011541 reaction mixture Substances 0.000 description 30
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 28
229910052943 magnesium sulfate Inorganic materials 0.000 description 26
235000019341 magnesium sulphate Nutrition 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
238000001914 filtration Methods 0.000 description 24
238000004458 analytical method Methods 0.000 description 22
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 21
239000000725 suspension Substances 0.000 description 21
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
229910000041 hydrogen chloride Inorganic materials 0.000 description 20
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
239000000284 extract Substances 0.000 description 19
239000000047 product Substances 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
238000010992 reflux Methods 0.000 description 18
239000002904 solvent Substances 0.000 description 18
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
239000003480 eluent Substances 0.000 description 15
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
239000006260 foam Substances 0.000 description 13
239000012299 nitrogen atmosphere Substances 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
239000008346 aqueous phase Substances 0.000 description 9
239000004471 Glycine Substances 0.000 description 8
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
239000012267 brine Substances 0.000 description 7
239000003921 oil Substances 0.000 description 7
235000019198 oils Nutrition 0.000 description 7
239000012071 phase Substances 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
QCXRMHQLFIXXOV-UHFFFAOYSA-N 6,7-dichloro-2,3-dimethoxyquinoxalin-5-amine Chemical compound ClC1=C(Cl)C(N)=C2N=C(OC)C(OC)=NC2=C1 QCXRMHQLFIXXOV-UHFFFAOYSA-N 0.000 description 6
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 6
108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 6
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 6
239000010410 layer Substances 0.000 description 6
UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
239000007858 starting material Substances 0.000 description 6
238000003756 stirring Methods 0.000 description 6
238000001665 trituration Methods 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
SIPUZPBQZHNSDW-UHFFFAOYSA-N diisobutylaluminium hydride Substances CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
ABJFBJGGLJVMAQ-UHFFFAOYSA-N 1,4-dihydroquinoxaline-2,3-dione Chemical compound C1=CC=C2NC(=O)C(=O)NC2=C1 ABJFBJGGLJVMAQ-UHFFFAOYSA-N 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 4
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 4
IDYQIZJBJKKYES-UHFFFAOYSA-N 6,7-dichloro-2,3-dimethoxy-5-(3-pyridin-3-yl-1,2,4-triazol-4-yl)quinoxaline Chemical compound C=12N=C(OC)C(OC)=NC2=CC(Cl)=C(Cl)C=1N1C=NN=C1C1=CC=CN=C1 IDYQIZJBJKKYES-UHFFFAOYSA-N 0.000 description 4
GTALKZFSGGWCBU-UHFFFAOYSA-N 6,7-dichloro-2,3-dimethoxy-5-pyridin-4-ylquinoxaline Chemical compound C=12N=C(OC)C(OC)=NC2=CC(Cl)=C(Cl)C=1C1=CC=NC=C1 GTALKZFSGGWCBU-UHFFFAOYSA-N 0.000 description 4
NPKYOEDDHLWORX-UHFFFAOYSA-N 6,7-dichloro-2,3-dimethoxyquinoxaline Chemical compound ClC1=C(Cl)C=C2N=C(OC)C(OC)=NC2=C1 NPKYOEDDHLWORX-UHFFFAOYSA-N 0.000 description 4
TZCLYCXXYZEAKX-UHFFFAOYSA-N 6-chloro-2,3-dimethoxy-7-methylquinoxalin-5-amine Chemical compound CC1=C(Cl)C(N)=C2N=C(OC)C(OC)=NC2=C1 TZCLYCXXYZEAKX-UHFFFAOYSA-N 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
210000004556 brain Anatomy 0.000 description 4
239000012065 filter cake Substances 0.000 description 4
229960002989 glutamic acid Drugs 0.000 description 4
238000011065 in-situ storage 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
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229910001873 dinitrogen Inorganic materials 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
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239000012153 distilled water Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
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238000010931 ester hydrolysis Methods 0.000 description 1
125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
KLWYPRNPRNPORS-UHFFFAOYSA-N ethyl 1h-imidazole-5-carboxylate Chemical compound CCOC(=O)C1=CN=CN1 KLWYPRNPRNPORS-UHFFFAOYSA-N 0.000 description 1
ZLTQPKYWAMOOGD-UHFFFAOYSA-N ethyl 2-[4-(6,7-dichloro-2,3-dimethoxyquinoxalin-5-yl)-5-methyl-1,2,4-triazol-3-yl]acetate Chemical compound CCOC(=O)CC1=NN=C(C)N1C1=C(Cl)C(Cl)=CC2=NC(OC)=C(OC)N=C12 ZLTQPKYWAMOOGD-UHFFFAOYSA-N 0.000 description 1
UABZXMAUPKBULM-UHFFFAOYSA-N ethyl 2-phenyl-1h-imidazole-5-carboxylate Chemical compound N1C(C(=O)OCC)=CN=C1C1=CC=CC=C1 UABZXMAUPKBULM-UHFFFAOYSA-N 0.000 description 1
QKIHTRLAYJDJKE-UHFFFAOYSA-N ethyl 4-(6,7-dichloro-2,3-dimethoxyquinoxalin-5-yl)-1,2,4-triazole-3-carboxylate Chemical compound CCOC(=O)C1=NN=CN1C1=C(Cl)C(Cl)=CC2=NC(OC)=C(OC)N=C12 QKIHTRLAYJDJKE-UHFFFAOYSA-N 0.000 description 1
TXHKICGVVGEHBN-UHFFFAOYSA-N ethyl 5-methyl-1h-1,2,4-triazole-3-carboxylate Chemical compound CCOC(=O)C1=NNC(C)=N1 TXHKICGVVGEHBN-UHFFFAOYSA-N 0.000 description 1
IKHQUQSZIPLOLJ-UHFFFAOYSA-N ethyl 6-phenylpyridine-3-carboxylate Chemical compound N1=CC(C(=O)OCC)=CC=C1C1=CC=CC=C1 IKHQUQSZIPLOLJ-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
VYSYZMNJHYOXGN-UHFFFAOYSA-N ethyl n-aminocarbamate Chemical compound CCOC(=O)NN VYSYZMNJHYOXGN-UHFFFAOYSA-N 0.000 description 1
PYFMAAFCQDFHJX-UHFFFAOYSA-N ethyl pyrimidine-2-carboxylate Chemical compound CCOC(=O)C1=NC=CC=N1 PYFMAAFCQDFHJX-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000002461 excitatory amino acid Effects 0.000 description 1
239000003257 excitatory amino acid Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
230000006870 function Effects 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
239000008103 glucose Substances 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
239000008241 heterogeneous mixture Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
JXYZHMPRERWTPM-UHFFFAOYSA-N hydron;morpholine;chloride Chemical compound Cl.C1COCCN1 JXYZHMPRERWTPM-UHFFFAOYSA-N 0.000 description 1
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
230000003993 interaction Effects 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229960003299 ketamine Drugs 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
CHFSOFHQIZKQCR-UHFFFAOYSA-N licostinel Chemical compound N1C(=O)C(=O)NC2=C1C=C(Cl)C(Cl)=C2[N+](=O)[O-] CHFSOFHQIZKQCR-UHFFFAOYSA-N 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
238000005567 liquid scintillation counting Methods 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
YTJXGDYAEOTOCG-UHFFFAOYSA-N lithium;di(propan-2-yl)azanide;oxolane Chemical compound [Li+].C1CCOC1.CC(C)[N-]C(C)C YTJXGDYAEOTOCG-UHFFFAOYSA-N 0.000 description 1
239000006210 lotion Substances 0.000 description 1
208000002780 macular degeneration Diseases 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
102000006239 metabotropic receptors Human genes 0.000 description 1
108020004083 metabotropic receptors Proteins 0.000 description 1
229910021645 metal ion Inorganic materials 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
RHMQNXNXUZLEIY-UHFFFAOYSA-N methanol;2-propan-2-yloxypropane Chemical compound OC.CC(C)OC(C)C RHMQNXNXUZLEIY-UHFFFAOYSA-N 0.000 description 1
NSLZRXJBVCDRAW-UHFFFAOYSA-N methyl 2-[5-(6,7-dichloro-2,3-dioxo-1,4-dihydroquinoxalin-5-yl)tetrazol-1-yl]acetate Chemical compound COC(=O)CN1N=NN=C1C1=C(Cl)C(Cl)=CC2=C1NC(=O)C(=O)N2 NSLZRXJBVCDRAW-UHFFFAOYSA-N 0.000 description 1
BNUSGSIKVOXDAZ-UHFFFAOYSA-N methyl 5-(hydrazinecarbonyl)pyridine-2-carboxylate Chemical compound COC(=O)C1=CC=C(C(=O)NN)C=N1 BNUSGSIKVOXDAZ-UHFFFAOYSA-N 0.000 description 1
238000004452 microanalysis Methods 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000003541 multi-stage reaction Methods 0.000 description 1
AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 1
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125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000016273 neuron death Effects 0.000 description 1
230000002887 neurotoxic effect Effects 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000003883 ointment base Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
210000000578 peripheral nerve Anatomy 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
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150000003141 primary amines Chemical class 0.000 description 1
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208000020016 psychiatric disease Diseases 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
KFUSANSHCADHNJ-UHFFFAOYSA-N pyridine-3-carbohydrazide Chemical compound NNC(=O)C1=CC=CN=C1 KFUSANSHCADHNJ-UHFFFAOYSA-N 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
DQEIYNHQKWEZKR-UHFFFAOYSA-N pyrimidine-2-carbohydrazide Chemical compound NNC(=O)C1=NC=CC=N1 DQEIYNHQKWEZKR-UHFFFAOYSA-N 0.000 description 1
125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 description 1
SAAYZFAHJFPOHZ-UHFFFAOYSA-N quinoxalin-5-amine Chemical compound C1=CN=C2C(N)=CC=CC2=N1 SAAYZFAHJFPOHZ-UHFFFAOYSA-N 0.000 description 1
150000003252 quinoxalines Chemical class 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000002207 retinal effect Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
238000007363 ring formation reaction Methods 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
150000003335 secondary amines Chemical class 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
239000011734 sodium Substances 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
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
239000004296 sodium metabisulphite Substances 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
FHLDWQLHDYCXKI-UHFFFAOYSA-N sodium;4-(3,5-dichloro-4-hydroxyphenyl)iminocyclohexa-2,5-dien-1-one Chemical compound [Na+].C1=C(Cl)C(O)=C(Cl)C=C1N=C1C=CC(=O)C=C1 FHLDWQLHDYCXKI-UHFFFAOYSA-N 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
235000011150 stannous chloride Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
150000003892 tartrate salts Chemical class 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
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
231100000886 tinnitus Toxicity 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
COHOGNZHAUOXPA-UHFFFAOYSA-N trimethyl(phenyl)stannane Chemical compound C[Sn](C)(C)C1=CC=CC=C1 COHOGNZHAUOXPA-UHFFFAOYSA-N 0.000 description 1
UYPYRKYUKCHHIB-UHFFFAOYSA-N trimethylamine N-oxide Chemical compound C[N+](C)(C)[O-] UYPYRKYUKCHHIB-UHFFFAOYSA-N 0.000 description 1
PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
229940045860 white wax Drugs 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Rheumatology (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Psychology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Luminescent Compositions (AREA)
Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)

SK1214-98A 1996-03-09 1997-02-27 Chinoxalíndióny, spôsob a medziprodukty na ich výrobu, ich použitie a farmaceutické kompozície na ich báze SK283467B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9605027.3A GB9605027D0 (en)	1996-03-09	1996-03-09	Quinoxalinediones
PCT/EP1997/000995 WO1997032873A1 (en)	1996-03-09	1997-02-27	Quinoxalinediones

Publications (2)

Publication Number	Publication Date
SK121498A3 SK121498A3 (en)	2000-10-09
SK283467B6 true SK283467B6 (sk)	2003-08-05

Family

ID=10790134

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1214-98A SK283467B6 (sk)	1996-03-09	1997-02-27	Chinoxalíndióny, spôsob a medziprodukty na ich výrobu, ich použitie a farmaceutické kompozície na ich báze

Country Status (42)

Country	Link
US (1)	US6376490B1 (da)
EP (1)	EP0885212B1 (da)
JP (1)	JP3110467B2 (da)
KR (1)	KR100288099B1 (da)
CN (1)	CN1103770C (da)
AP (1)	AP767A (da)
AR (1)	AR006119A1 (da)
AT (1)	ATE208773T1 (da)
AU (1)	AU717972B2 (da)
BG (1)	BG63340B1 (da)
BR (1)	BR9707851A (da)
CA (1)	CA2248366C (da)
CO (1)	CO4770976A1 (da)
CZ (1)	CZ292792B6 (da)
DE (1)	DE69708269T2 (da)
DK (1)	DK0885212T3 (da)
DZ (1)	DZ2188A1 (da)
EA (1)	EA001730B1 (da)
ES (1)	ES2163742T3 (da)
GB (1)	GB9605027D0 (da)
HN (1)	HN1998000034A (da)
HR (1)	HRP970132A2 (da)
HU (1)	HUP9900975A3 (da)
ID (1)	ID18112A (da)
IL (1)	IL125491A (da)
IS (1)	IS4811A (da)
MA (1)	MA26422A1 (da)
NO (1)	NO984058L (da)
NZ (1)	NZ331060A (da)
OA (1)	OA10850A (da)
PE (2)	PE43398A1 (da)
PL (1)	PL329032A1 (da)
PT (1)	PT885212E (da)
SI (1)	SI0885212T1 (da)
SK (1)	SK283467B6 (da)
TN (1)	TNSN97044A1 (da)
TR (1)	TR199801782T2 (da)
TW (1)	TW454004B (da)
UY (1)	UY24482A1 (da)
WO (1)	WO1997032873A1 (da)
YU (2)	YU39698A (da)
ZA (1)	ZA971987B (da)

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WO2005006945A2 (en) *	2003-07-03	2005-01-27	The Salk Institute For Biological Studies	Methods for treating neural disorders and compounds useful therefor
MY145368A (en) *	2004-01-13	2012-01-31	Nissan Chemical Ind Ltd	Aminoquinoxaline compounds and polyaminoquinoxaline compounds, and use thereof
CN1926647B (zh)	2004-02-06	2010-04-14	国立大学法人山口大学	储能装置用电极及其制造方法
JP2007223901A (ja) *	2004-03-24	2007-09-06	Takeda Chem Ind Ltd	複素環化合物およびその用途
US20060211739A1 (en) *	2005-02-08	2006-09-21	Arturo Perez-Medrano	Use of selective P2X7 receptor antagonists
WO2007112347A1 (en) *	2006-03-28	2007-10-04	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
WO2008055945A1 (en)	2006-11-09	2008-05-15	Probiodrug Ag	3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases
SI2091948T1 (sl)	2006-11-30	2012-07-31	Probiodrug Ag	Novi inhibitorji glutaminil ciklaze
US8603980B2 (en)	2007-01-16	2013-12-10	The Johns Hopkins University	Glutamate receptor antagonists and methods of use
ZA200905537B (en)	2007-03-01	2010-10-27	Probiodrug Ag	New use of glutaminyl cyclase inhibitors
EP2142514B1 (en)	2007-04-18	2014-12-24	Probiodrug AG	Thiourea derivatives as glutaminyl cyclase inhibitors
CN110724124A (zh) *	2007-05-17	2020-01-24	株式会社半导体能源研究所	***衍生物
ES2548913T3 (es)	2009-09-11	2015-10-21	Probiodrug Ag	Derivados heterocíclicos como inhibidores de glutaminil ciclasa
JP6026284B2 (ja)	2010-03-03	2016-11-16	プロビオドルグエージー	グルタミニルシクラーゼの阻害剤
JP5688745B2 (ja)	2010-03-10	2015-03-25	プロビオドルグエージー	グルタミニルシクラーゼ（ｑｃ、ｅｃ２．３．２．５）の複素環阻害剤
WO2011131748A2 (en)	2010-04-21	2011-10-27	Probiodrug Ag	Novel inhibitors
WO2012123563A1 (en)	2011-03-16	2012-09-20	Probiodrug Ag	Benz imidazole derivatives as inhibitors of glutaminyl cyclase
JP2016507537A (ja) *	2013-02-07	2016-03-10	メルクパテントゲゼルシャフトミットベシュレンクテルハフツングＭｅｒｃｋＰａｔｅｎｔＧｅｓｅｌｌｓｃｈａｆｔｍｉｔｂｅｓｃｈｒａｅｎｋｔｅｒＨａｆｔｕｎｇ	置換アセチレン誘導体およびｍＧｌｕＲ４の正のアロステリックモジュレーターとしてのそれらの使用
EP3461819B1 (en)	2017-09-29	2020-05-27	Probiodrug AG	Inhibitors of glutaminyl cyclase
CN111548320B (zh) *	2019-10-09	2023-03-24	贵州大学	一类1，3，4-噁二唑酰肼类化合物及其制备方法和应用

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1996
- 1996-03-09 GB GBGB9605027.3A patent/GB9605027D0/en active Pending
1997
- 1997-02-05 TW TW086101412A patent/TW454004B/zh not_active IP Right Cessation
- 1997-02-27 AU AU20231/97A patent/AU717972B2/en not_active Ceased
- 1997-02-27 SI SI9730225T patent/SI0885212T1/xx unknown
- 1997-02-27 PL PL97329032A patent/PL329032A1/xx unknown
- 1997-02-27 IL IL12549197A patent/IL125491A/xx not_active IP Right Cessation
- 1997-02-27 BR BR9707851A patent/BR9707851A/pt not_active Application Discontinuation
- 1997-02-27 JP JP09531429A patent/JP3110467B2/ja not_active Expired - Fee Related
- 1997-02-27 WO PCT/EP1997/000995 patent/WO1997032873A1/en active IP Right Grant
- 1997-02-27 SK SK1214-98A patent/SK283467B6/sk unknown
- 1997-02-27 CZ CZ19982864A patent/CZ292792B6/cs not_active IP Right Cessation
- 1997-02-27 ES ES97908156T patent/ES2163742T3/es not_active Expired - Lifetime
- 1997-02-27 NZ NZ331060A patent/NZ331060A/xx unknown
- 1997-02-27 AT AT97908156T patent/ATE208773T1/de not_active IP Right Cessation
- 1997-02-27 EA EA199800702A patent/EA001730B1/ru not_active IP Right Cessation
- 1997-02-27 DK DK97908156T patent/DK0885212T3/da active
- 1997-02-27 CN CN97192923A patent/CN1103770C/zh not_active Expired - Fee Related
- 1997-02-27 EP EP97908156A patent/EP0885212B1/en not_active Expired - Lifetime
- 1997-02-27 YU YU39698A patent/YU39698A/sh unknown
- 1997-02-27 DE DE69708269T patent/DE69708269T2/de not_active Expired - Fee Related
- 1997-02-27 TR TR1998/01782T patent/TR199801782T2/xx unknown
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- 1997-02-27 CA CA002248366A patent/CA2248366C/en not_active Expired - Fee Related
- 1997-02-27 HU HU9900975A patent/HUP9900975A3/hu unknown
- 1997-02-27 KR KR1019980707063A patent/KR100288099B1/ko not_active IP Right Cessation
- 1997-03-05 TN TNTNSN97044A patent/TNSN97044A1/fr unknown
- 1997-03-05 DZ DZ970034A patent/DZ2188A1/fr active
- 1997-03-05 AR ARP970100888A patent/AR006119A1/es unknown
- 1997-03-05 MA MA24514A patent/MA26422A1/fr unknown
- 1997-03-06 AP APAP/P/1997/000947A patent/AP767A/en active
- 1997-03-06 PE PE1997000162A patent/PE43398A1/es not_active Application Discontinuation
- 1997-03-06 UY UY24482A patent/UY24482A1/es not_active IP Right Cessation
- 1997-03-07 ZA ZA971987A patent/ZA971987B/xx unknown
- 1997-03-07 ID IDP970725A patent/ID18112A/id unknown
- 1997-03-07 HR HR9605027.3A patent/HRP970132A2/xx not_active Application Discontinuation
- 1997-03-10 CO CO97012901A patent/CO4770976A1/es unknown
1998
- 1998-02-19 HN HN1998000034A patent/HN1998000034A/es unknown
- 1998-02-23 PE PE1998000128A patent/PE58199A1/es not_active Application Discontinuation
- 1998-02-24 YU YU41199A patent/YU41199A/sh unknown
- 1998-07-27 IS IS4811A patent/IS4811A/is unknown
- 1998-08-28 OA OA9800155A patent/OA10850A/en unknown
- 1998-09-03 NO NO984058A patent/NO984058L/no unknown
- 1998-09-04 US US09/157,806 patent/US6376490B1/en not_active Expired - Fee Related
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Also Published As

Publication number	Publication date
DZ2188A1 (fr)	2002-12-02
EP0885212A1 (en)	1998-12-23
AP767A (en)	1999-09-29
GB9605027D0 (en)	1996-05-08
CN1213369A (zh)	1999-04-07
CA2248366C (en)	2002-06-04
TR199801782T2 (xx)	1998-12-21
AU717972B2 (en)	2000-04-06
AU2023197A (en)	1997-09-22
YU39698A (sh)	1999-03-04
MA26422A1 (fr)	2004-12-20
ID18112A (id)	1998-03-05
HRP970132A2 (en)	1998-06-30
IS4811A (is)	1998-07-27
CO4770976A1 (es)	1999-04-30
WO1997032873A1 (en)	1997-09-12
HUP9900975A3 (en)	2001-12-28
PE58199A1 (es)	1999-06-11
DE69708269T2 (de)	2002-07-25
EA199800702A1 (ru)	1999-04-29
ES2163742T3 (es)	2002-02-01
CZ292792B6 (cs)	2003-12-17
AP9700947A0 (en)	1997-04-30
NO984058D0 (no)	1998-09-03
JPH11506123A (ja)	1999-06-02
OA10850A (en)	2001-08-16
EP0885212B1 (en)	2001-11-14
CN1103770C (zh)	2003-03-26
KR100288099B1 (ko)	2001-05-02
US6376490B1 (en)	2002-04-23
TW454004B (en)	2001-09-11
DK0885212T3 (da)	2002-03-25
NZ331060A (en)	2000-01-28
CA2248366A1 (en)	1997-09-12
ATE208773T1 (de)	2001-11-15
IL125491A0 (en)	1999-03-12
HUP9900975A2 (hu)	1999-07-28
YU41199A (sh)	2001-09-28
TNSN97044A1 (fr)	2005-03-15
SI0885212T1 (en)	2002-02-28
ZA971987B (en)	1998-09-07
PT885212E (pt)	2002-02-28
BR9707851A (pt)	1999-07-27
JP3110467B2 (ja)	2000-11-20
PL329032A1 (en)	1999-03-01
IL125491A (en)	2003-07-06
UY24482A1 (es)	2000-09-29
AR006119A1 (es)	1999-08-11
HN1998000034A (es)	1999-02-09
NO984058L (no)	1998-11-06
BG63340B1 (bg)	2001-10-31
SK121498A3 (en)	2000-10-09
CZ286498A3 (cs)	1999-07-14
BG102760A (en)	1999-09-30
KR19990087614A (ko)	1999-12-27
EA001730B1 (ru)	2001-08-27
DE69708269D1 (de)	2001-12-20
PE43398A1 (es)	1998-08-29

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