NO312961B1 - 3-alkoksyisoksazol-4-yl-substituerte 2- aminokarboksylsyreforbindelser - Google Patents
3-alkoksyisoksazol-4-yl-substituerte 2- aminokarboksylsyreforbindelser Download PDFInfo
- Publication number
- NO312961B1 NO312961B1 NO19991561A NO991561A NO312961B1 NO 312961 B1 NO312961 B1 NO 312961B1 NO 19991561 A NO19991561 A NO 19991561A NO 991561 A NO991561 A NO 991561A NO 312961 B1 NO312961 B1 NO 312961B1
- Authority
- NO
- Norway
- Prior art keywords
- group
- alkyl
- hydrogen
- amino
- mmol
- Prior art date
Links
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 24
- 239000001257 hydrogen Substances 0.000 claims abstract description 23
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 8
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 8
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 7
- 206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 7
- 208000023105 Huntington disease Diseases 0.000 claims abstract description 7
- 208000002193 Pain Diseases 0.000 claims abstract description 7
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 7
- 230000036506 anxiety Effects 0.000 claims abstract description 7
- 208000035475 disorder Diseases 0.000 claims abstract description 7
- 230000001037 epileptic effect Effects 0.000 claims abstract description 7
- 201000006474 Brain Ischemia Diseases 0.000 claims abstract description 6
- 206010008118 cerebral infarction Diseases 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 150000003463 sulfur Chemical class 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 102
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 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
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 125000006850 spacer group Chemical group 0.000 claims 1
- 239000003257 excitatory amino acid Substances 0.000 abstract description 22
- 230000002461 excitatory amino acid Effects 0.000 abstract description 22
- UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 abstract description 12
- 239000003446 ligand Substances 0.000 abstract description 12
- 102000003678 AMPA Receptors Human genes 0.000 abstract description 8
- 108090000078 AMPA Receptors Proteins 0.000 abstract description 8
- 125000000217 alkyl group Chemical group 0.000 abstract description 6
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 abstract description 5
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 3
- 125000004450 alkenylene group Chemical group 0.000 abstract 2
- 125000004419 alkynylene group Chemical group 0.000 abstract 2
- 125000001931 aliphatic group Chemical group 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000000304 alkynyl group Chemical group 0.000 abstract 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 abstract 1
- 125000005842 heteroatom Chemical group 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- 125000003831 tetrazolyl group Chemical group 0.000 abstract 1
- 125000001425 triazolyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 64
- 239000000203 mixture Substances 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- 229910001868 water Inorganic materials 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 238000000034 method Methods 0.000 description 29
- 235000019439 ethyl acetate Nutrition 0.000 description 28
- 239000000243 solution Substances 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 239000008346 aqueous phase Substances 0.000 description 16
- -1 bicyclic AMPA analogs Chemical class 0.000 description 15
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 239000000284 extract Substances 0.000 description 14
- 239000012267 brine Substances 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000003480 eluent Substances 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- 238000010511 deprotection reaction Methods 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- 239000011260 aqueous acid Substances 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 235000019260 propionic acid Nutrition 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 230000029936 alkylation Effects 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 5
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical group O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- 229910004298 SiO 2 Inorganic materials 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 229950005499 carbon tetrachloride Drugs 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- SASIKKFHZDUYDD-UHFFFAOYSA-N 4-(2-amino-2-carboxyethyl)-3-ethoxy-1,2-oxazole-5-carboxylic acid Chemical compound CCOC1=NOC(C(O)=O)=C1CC(N)C(O)=O SASIKKFHZDUYDD-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000819038 Chichester Species 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- HEMHJVSKTPXQMS-DYCDLGHISA-M Sodium hydroxide-d Chemical compound [Na+].[2H][O-] HEMHJVSKTPXQMS-DYCDLGHISA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- ISOLMABRZPQKOV-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate Chemical compound CCOC(=O)C(NC(C)=O)C(=O)OCC ISOLMABRZPQKOV-UHFFFAOYSA-N 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- UVXYNACCCGVAGC-UHFFFAOYSA-N ethyl 3-methoxy-4-methyl-1,2-oxazole-5-carboxylate Chemical compound CCOC(=O)C=1ON=C(OC)C=1C UVXYNACCCGVAGC-UHFFFAOYSA-N 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 230000001404 mediated effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 230000005062 synaptic transmission Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- HRABDFMAJHJCGR-UHFFFAOYSA-N 3-ethoxy-4-methyl-1,2-oxazole-5-carboxylic acid Chemical compound CCOC1=NOC(C(O)=O)=C1C HRABDFMAJHJCGR-UHFFFAOYSA-N 0.000 description 2
- VZRWHHRVIVIAKL-UHFFFAOYSA-N 3-ethoxy-4-methyl-5-(1h-1,2,4-triazol-5-yl)-1,2-oxazole Chemical compound CCOC1=NOC(C2=NNC=N2)=C1C VZRWHHRVIVIAKL-UHFFFAOYSA-N 0.000 description 2
- HZBMNMUXABPUSY-UHFFFAOYSA-N 4-(2-amino-3-ethoxy-3-oxopropyl)-3-ethoxy-1,2-oxazole-5-carboxylic acid Chemical compound CCOC(=O)C(N)CC=1C(OCC)=NOC=1C(O)=O HZBMNMUXABPUSY-UHFFFAOYSA-N 0.000 description 2
- KBLLNWAYELJWKQ-UHFFFAOYSA-N 4-(aminomethyl)-3-ethoxy-1,2-oxazole-5-carboxylic acid;hydrochloride Chemical compound Cl.CCOC1=NOC(C(O)=O)=C1CN KBLLNWAYELJWKQ-UHFFFAOYSA-N 0.000 description 2
- IWOIZXOSUGOHLX-UHFFFAOYSA-N 4-(bromomethyl)-3-ethoxy-5-(1-trityl-1,2,4-triazol-3-yl)-1,2-oxazole Chemical compound CCOC1=NOC(C2=NN(C=N2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1CBr IWOIZXOSUGOHLX-UHFFFAOYSA-N 0.000 description 2
- SASIKKFHZDUYDD-YFKPBYRVSA-N 4-[(2s)-2-amino-2-carboxyethyl]-3-ethoxy-1,2-oxazole-5-carboxylic acid Chemical compound CCOC1=NOC(C(O)=O)=C1C[C@H](N)C(O)=O SASIKKFHZDUYDD-YFKPBYRVSA-N 0.000 description 2
- DWTZVYMPDOFFKB-UHFFFAOYSA-N 4-[2-carboxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]-3-ethoxy-1,2-oxazole-5-carboxylic acid Chemical compound CCOC1=NOC(C(O)=O)=C1CC(NC(=O)OC(C)(C)C)C(O)=O DWTZVYMPDOFFKB-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010011953 Decreased activity Diseases 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102000018899 Glutamate Receptors Human genes 0.000 description 2
- 108010027915 Glutamate Receptors Proteins 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000001054 cortical effect Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- RONPLVSBICGMPV-UHFFFAOYSA-N ethyl 2-benzyl-4-[3-ethoxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]-3-oxo-1,2-oxazole-5-carboxylate Chemical compound O=C1C(CC(C(=O)OCC)NC(=O)OC(C)(C)C)=C(C(=O)OCC)ON1CC1=CC=CC=C1 RONPLVSBICGMPV-UHFFFAOYSA-N 0.000 description 2
- ZIGVIPHWBDVWCN-UHFFFAOYSA-N ethyl 4-[3-ethoxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropyl]-3-oxo-1,2-oxazole-5-carboxylate Chemical compound CC(C)(C)OC(=O)NC(C(=O)OCC)CC=1C(O)=NOC=1C(=O)OCC ZIGVIPHWBDVWCN-UHFFFAOYSA-N 0.000 description 2
- MTCRWLJMWQRTFM-UHFFFAOYSA-N ethyl 4-methyl-3-oxo-1,2-oxazole-5-carboxylate Chemical compound CCOC(=O)C=1ONC(=O)C=1C MTCRWLJMWQRTFM-UHFFFAOYSA-N 0.000 description 2
- 230000003492 excitotoxic effect Effects 0.000 description 2
- 231100000063 excitotoxicity Toxicity 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- IXXFONLVFCLWJF-UHFFFAOYSA-N n-(dimethylaminomethylidene)-3-ethoxy-4-methyl-1,2-oxazole-5-carboxamide Chemical compound CCOC1=NOC(C(=O)N=CN(C)C)=C1C IXXFONLVFCLWJF-UHFFFAOYSA-N 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- FCFWEOGTZZPCTO-QMMMGPOBSA-N (2s)-3,6-dimethoxy-2-propan-2-yl-2,5-dihydropyrazine Chemical compound COC1=N[C@@H](C(C)C)C(OC)=NC1 FCFWEOGTZZPCTO-QMMMGPOBSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- MCCCJBNRMFLROD-UHFFFAOYSA-N 1,2-oxazole-5-carbonitrile Chemical compound N#CC1=CC=NO1 MCCCJBNRMFLROD-UHFFFAOYSA-N 0.000 description 1
- MIIQJAUWHSUTIT-UHFFFAOYSA-N 1,2-oxazole-5-carboxylic acid Chemical group OC(=O)C1=CC=NO1 MIIQJAUWHSUTIT-UHFFFAOYSA-N 0.000 description 1
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- JCXLPVAAGYNKBT-UHFFFAOYSA-N 2-amino-3-(3-oxo-5-phenyl-1,2-oxazol-4-yl)propanoic acid Chemical compound OC1=NOC(C=2C=CC=CC=2)=C1CC(N)C(O)=O JCXLPVAAGYNKBT-UHFFFAOYSA-N 0.000 description 1
- PIXJURSCCVBKRF-UHFFFAOYSA-N 2-amino-3-(5-tert-butyl-3-oxo-4-isoxazolyl)propanoic acid Chemical compound CC(C)(C)C=1ONC(=O)C=1CC([NH3+])C([O-])=O PIXJURSCCVBKRF-UHFFFAOYSA-N 0.000 description 1
- 125000003504 2-oxazolinyl group Chemical group O1C(=NCC1)* 0.000 description 1
- RMMBULJTXVBMPL-UHFFFAOYSA-N 3-amino-4-ethoxycyclobut-3-ene-1,2-dione Chemical compound CCOC1=C(N)C(=O)C1=O RMMBULJTXVBMPL-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- BAFVEJBFCGDCRA-UHFFFAOYSA-N 3-ethoxy-4-methyl-1,2-oxazole-5-carbonitrile Chemical compound CCOC1=NOC(C#N)=C1C BAFVEJBFCGDCRA-UHFFFAOYSA-N 0.000 description 1
- QFOSZIZURGAVQU-UHFFFAOYSA-N 3-ethoxy-4-methyl-1,2-oxazole-5-carboxamide Chemical compound CCOC1=NOC(C(N)=O)=C1C QFOSZIZURGAVQU-UHFFFAOYSA-N 0.000 description 1
- JWVRFYBAWHOIIX-UHFFFAOYSA-N 3-ethoxy-4-methyl-5-(1-trityl-1,2,4-triazol-3-yl)-1,2-oxazole Chemical compound CCOC1=NOC(C2=NN(C=N2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1C JWVRFYBAWHOIIX-UHFFFAOYSA-N 0.000 description 1
- UAZBNYQNVJZSSU-UHFFFAOYSA-N 4-(2-amino-2-carboxyethyl)-2-ethyl-3-oxo-1,2-oxazole-5-carboxylic acid;hydrate Chemical compound O.CCN1OC(C(O)=O)=C(CC(N)C(O)=O)C1=O UAZBNYQNVJZSSU-UHFFFAOYSA-N 0.000 description 1
- DPLVVDCJEXFWPF-UHFFFAOYSA-N 4-(2-amino-2-carboxyethyl)-3-methoxy-1,2-oxazole-5-carboxylic acid;hydrate Chemical compound O.COC1=NOC(C(O)=O)=C1CC(N)C(O)=O DPLVVDCJEXFWPF-UHFFFAOYSA-N 0.000 description 1
- FXQOALFIXYDQLV-UHFFFAOYSA-N 4-(2-amino-2-carboxyethyl)-3-oxo-1,2-oxazole-5-carboxylic acid;hydrate Chemical compound O.OC(=O)C(N)CC=1C(O)=NOC=1C(O)=O FXQOALFIXYDQLV-UHFFFAOYSA-N 0.000 description 1
- HPYZKSSOZWJEFB-UHFFFAOYSA-N 4-(2-amino-2-carboxyethyl)-3-phenylmethoxy-1,2-oxazole-5-carboxylic acid Chemical compound O1C(C(O)=O)=C(CC(N)C(O)=O)C(OCC=2C=CC=CC=2)=N1 HPYZKSSOZWJEFB-UHFFFAOYSA-N 0.000 description 1
- OHAFCSNDJBQSTL-UHFFFAOYSA-N 4-(2-amino-2-carboxyethyl)-3-propan-2-yloxy-1,2-oxazole-5-carboxylic acid Chemical compound CC(C)OC1=NOC(C(O)=O)=C1CC(N)C(O)=O OHAFCSNDJBQSTL-UHFFFAOYSA-N 0.000 description 1
- VHWFNFITHSPBSR-UHFFFAOYSA-N 4-methyl-1,2-oxazole Chemical group CC=1C=NOC=1 VHWFNFITHSPBSR-UHFFFAOYSA-N 0.000 description 1
- QJTFZONAUNJXEC-UHFFFAOYSA-N 4-methyl-3-oxo-1,2-oxazole-5-carboxylic acid Chemical compound CC1=C(C(O)=O)ONC1=O QJTFZONAUNJXEC-UHFFFAOYSA-N 0.000 description 1
- FWTVMIDLZDRJTQ-UHFFFAOYSA-N 5-(4,4-dimethyl-5h-1,3-oxazol-2-yl)-3-ethoxy-4-methyl-1,2-oxazole Chemical compound CCOC1=NOC(C=2OCC(C)(C)N=2)=C1C FWTVMIDLZDRJTQ-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 229940124118 AMPA receptor agonist Drugs 0.000 description 1
- 239000000774 AMPA receptor agonist Substances 0.000 description 1
- 229940098747 AMPA receptor antagonist Drugs 0.000 description 1
- 101001006370 Actinobacillus suis Hemolysin Proteins 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 206010003497 Asphyxia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000005642 Gabriel synthesis reaction Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 101001090860 Homo sapiens Myeloblastin Proteins 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- 102000000079 Kainic Acid Receptors Human genes 0.000 description 1
- 108010069902 Kainic Acid Receptors Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102100034681 Myeloblastin Human genes 0.000 description 1
- 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 1
- 229940127523 NMDA Receptor Antagonists Drugs 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003194 amino acid receptor blocking agent Substances 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- GLGAUBPACOBAMV-DOFZRALJSA-N arachidonylcyclopropylamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NC1CC1 GLGAUBPACOBAMV-DOFZRALJSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 101150088806 atpA gene Proteins 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- PDAUZKJUHPGECB-UHFFFAOYSA-N benzyl 3-ethoxy-4-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxo-3-phenylmethoxypropyl]-1,2-oxazole-5-carboxylate Chemical compound C=1C=CC=CC=1COC(=O)C(NC(=O)OC(C)(C)C)CC=1C(OCC)=NOC=1C(=O)OCC1=CC=CC=C1 PDAUZKJUHPGECB-UHFFFAOYSA-N 0.000 description 1
- FTYPKKQRZFLQJT-UHFFFAOYSA-N benzyl 4-(2-amino-3-oxo-3-phenylmethoxypropyl)-3-ethoxy-1,2-oxazole-5-carboxylate;hydrochloride Chemical compound Cl.C=1C=CC=CC=1COC(=O)C(N)CC=1C(OCC)=NOC=1C(=O)OCC1=CC=CC=C1 FTYPKKQRZFLQJT-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- CGGDEQIMUHPVQL-UHFFFAOYSA-N diethyl 2-acetamido-2-[[3-ethoxy-5-(1-trityl-1,2,4-triazol-3-yl)-1,2-oxazol-4-yl]methyl]propanedioate Chemical compound CCOC1=NOC(C2=NN(C=N2)C(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1CC(C(=O)OCC)(NC(C)=O)C(=O)OCC CGGDEQIMUHPVQL-UHFFFAOYSA-N 0.000 description 1
- PRHRASQAOFVJNY-UHFFFAOYSA-N diethyl 2-acetamido-2-[[3-ethoxy-5-(2h-tetrazol-5-yl)-1,2-oxazol-4-yl]methyl]propanedioate Chemical compound CCOC1=NOC(C=2NN=NN=2)=C1CC(C(=O)OCC)(NC(C)=O)C(=O)OCC PRHRASQAOFVJNY-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- WBVITBVRWAECCJ-UHFFFAOYSA-N ethyl 4-(2-amino-3-ethoxy-3-oxopropyl)-3-oxo-1,2-oxazole-5-carboxylate Chemical compound CCOC(=O)C(N)CC=1C(O)=NOC=1C(=O)OCC WBVITBVRWAECCJ-UHFFFAOYSA-N 0.000 description 1
- UVSBZQVLQWZJDB-UHFFFAOYSA-N ethyl 4-(bromomethyl)-3-ethoxy-1,2-oxazole-5-carboxylate Chemical compound CCOC(=O)C=1ON=C(OCC)C=1CBr UVSBZQVLQWZJDB-UHFFFAOYSA-N 0.000 description 1
- UWLHHCGAUCRMGC-UHFFFAOYSA-N ethyl 4-(bromomethyl)-3-methoxy-1,2-oxazole-5-carboxylate Chemical compound CCOC(=O)C=1ON=C(OC)C=1CBr UWLHHCGAUCRMGC-UHFFFAOYSA-N 0.000 description 1
- CQQBVORPSUQHME-UHFFFAOYSA-N ethyl 4-[(1,3-dioxoisoindol-2-yl)methyl]-3-ethoxy-1,2-oxazole-5-carboxylate Chemical compound O1N=C(OCC)C(CN2C(C3=CC=CC=C3C2=O)=O)=C1C(=O)OCC CQQBVORPSUQHME-UHFFFAOYSA-N 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 239000000928 excitatory amino acid agonist Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 150000001469 hydantoins Chemical class 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
- 229950006874 kainic acid Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 102000006239 metabotropic receptors Human genes 0.000 description 1
- 108020004083 metabotropic receptors Proteins 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- RGUOJYYIMVSCNC-UHFFFAOYSA-N n,n-dimethylformamide;2-methylpropanoic acid Chemical compound CN(C)C=O.CC(C)C(O)=O RGUOJYYIMVSCNC-UHFFFAOYSA-N 0.000 description 1
- 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
- 230000001722 neurochemical effect Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 231100000501 nonneurotoxic Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 229940124606 potential therapeutic agent Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 150000005375 primary alkyl halides Chemical class 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- GYPZFDNQZCSGND-UHFFFAOYSA-N propanoic acid;hydrate Chemical compound O.CCC(O)=O GYPZFDNQZCSGND-UHFFFAOYSA-N 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000011160 research 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
- 238000000926 separation method Methods 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000008293 synaptic mechanism Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
- C07D275/03—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/12—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK109296 | 1996-10-04 | ||
PCT/DK1997/000426 WO1998015542A1 (en) | 1996-10-04 | 1997-10-03 | 3-alkoxyisoxazol-4-yl-substituted 2-amino carboxylic acid compounds |
Publications (3)
Publication Number | Publication Date |
---|---|
NO991561D0 NO991561D0 (no) | 1999-03-30 |
NO991561L NO991561L (no) | 1999-06-04 |
NO312961B1 true NO312961B1 (no) | 2002-07-22 |
Family
ID=8100908
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO19991561A NO312961B1 (no) | 1996-10-04 | 1999-03-30 | 3-alkoksyisoksazol-4-yl-substituerte 2- aminokarboksylsyreforbindelser |
Country Status (26)
Country | Link |
---|---|
US (1) | US6200999B1 (xx) |
EP (1) | EP0934286B1 (xx) |
JP (1) | JP2001501630A (xx) |
KR (1) | KR20000048908A (xx) |
CN (1) | CN1238766A (xx) |
AR (1) | AR008880A1 (xx) |
AT (1) | ATE230734T1 (xx) |
AU (1) | AU733004B2 (xx) |
BG (1) | BG103348A (xx) |
BR (1) | BR9712198A (xx) |
CA (1) | CA2268028C (xx) |
CZ (1) | CZ116899A3 (xx) |
DE (1) | DE69718338T2 (xx) |
EA (1) | EA001625B1 (xx) |
ES (1) | ES2189978T3 (xx) |
HU (1) | HUP0000084A3 (xx) |
IL (1) | IL129135A0 (xx) |
IS (1) | IS5009A (xx) |
NO (1) | NO312961B1 (xx) |
NZ (1) | NZ334798A (xx) |
PL (1) | PL332553A1 (xx) |
SK (1) | SK42899A3 (xx) |
TR (1) | TR199900724T2 (xx) |
UA (1) | UA52698C2 (xx) |
WO (1) | WO1998015542A1 (xx) |
ZA (1) | ZA978877B (xx) |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
UA73749C2 (en) * | 1999-11-01 | 2005-09-15 | Diarylenines | |
US6495582B1 (en) * | 2000-09-15 | 2002-12-17 | Vertex Pharmaceuticals Incorporated | Isoxazole compositions useful as inhibitors of ERK |
US20040106794A1 (en) * | 2001-04-16 | 2004-06-03 | Schering Corporation | 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands |
UA78529C2 (en) | 2001-10-10 | 2007-04-10 | Wyeth Corp | Derivatives of [[2-(amino-3,4-dioxo-1-cyclobutene-1-yl)amino]alkyl] acid for treating pain |
US20040152694A1 (en) * | 2003-02-04 | 2004-08-05 | Istvan Kurucz | Methods and compositions for treating inflammatory disorders of the airways |
AU2004230895B2 (en) | 2003-04-09 | 2010-09-09 | Wyeth | Derivatives of 2-(8,9-dioxo-2,6-diazabicyclo(5.2.0)non-1(7)-en-2-yl)alkyl phosphonic acid and their use as N-methyl-D-aspartate (NMDA) receptor antagonists |
TW200514775A (en) | 2003-10-22 | 2005-05-01 | Wyeth Corp | Methods for the preparation of {2-[(8,9)-dioxo-2,6-diaza-bicyclo[5.2.0]-non-1(7)-en-2-yl]ethyl} phosphonic acid and esters thereof |
CA2625301A1 (en) * | 2005-10-11 | 2007-04-19 | F. Hoffmann-La Roche Ag | Isoxazole derivatives |
CN102066345B (zh) * | 2008-01-16 | 2013-07-17 | 生物科技研究有限公司 | *唑烷衍生物作为nmda拮抗剂 |
EP2338492A1 (en) | 2009-12-24 | 2011-06-29 | Universidad del Pais Vasco | Methods and compositions for the treatment of alzheimer |
TW201609719A (zh) | 2014-05-28 | 2016-03-16 | 美國禮來大藥廠 | 作為TARP-γ8依賴性AMPA受體拮抗劑之6-經取代-3H-1,3-苯并噻唑-2-酮化合物 |
KR102157528B1 (ko) * | 2016-01-21 | 2020-09-21 | 아구로카네쇼 가부시키가이샤 | 2-아미노니코틴산 벤질에스테르 유도체의 제조 방법 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0456519B1 (en) | 1990-05-11 | 1994-07-13 | Sankyo Company Limited | Piperidyloxy- and quinuclidinyloxy- isoxazole derivatives, their preparation and their therapeutic use |
WO1994010145A1 (en) | 1992-10-23 | 1994-05-11 | Merck Sharp & Dohme Limited | Dopamine receptor subtype ligands |
DK124393D0 (da) * | 1993-11-03 | 1993-11-03 | Lundbeck & Co As H | Compounds |
-
1997
- 1997-03-10 UA UA99042300A patent/UA52698C2/uk unknown
- 1997-10-03 AT AT97942821T patent/ATE230734T1/de not_active IP Right Cessation
- 1997-10-03 BR BR9712198-3A patent/BR9712198A/pt unknown
- 1997-10-03 EA EA199900358A patent/EA001625B1/ru not_active IP Right Cessation
- 1997-10-03 DE DE69718338T patent/DE69718338T2/de not_active Expired - Fee Related
- 1997-10-03 AU AU44517/97A patent/AU733004B2/en not_active Ceased
- 1997-10-03 PL PL97332553A patent/PL332553A1/xx unknown
- 1997-10-03 HU HU0000084A patent/HUP0000084A3/hu unknown
- 1997-10-03 SK SK428-99A patent/SK42899A3/sk unknown
- 1997-10-03 EP EP97942821A patent/EP0934286B1/en not_active Expired - Lifetime
- 1997-10-03 NZ NZ334798A patent/NZ334798A/en unknown
- 1997-10-03 AR ARP970104586A patent/AR008880A1/es not_active Application Discontinuation
- 1997-10-03 CA CA002268028A patent/CA2268028C/en not_active Expired - Fee Related
- 1997-10-03 CN CN97180167A patent/CN1238766A/zh active Pending
- 1997-10-03 WO PCT/DK1997/000426 patent/WO1998015542A1/en not_active Application Discontinuation
- 1997-10-03 TR TR1999/00724T patent/TR199900724T2/xx unknown
- 1997-10-03 CZ CZ991168A patent/CZ116899A3/cs unknown
- 1997-10-03 IL IL12913597A patent/IL129135A0/xx unknown
- 1997-10-03 ZA ZA9708877A patent/ZA978877B/xx unknown
- 1997-10-03 JP JP10517096A patent/JP2001501630A/ja active Pending
- 1997-10-03 KR KR1019990702938A patent/KR20000048908A/ko not_active Application Discontinuation
- 1997-10-03 US US09/269,356 patent/US6200999B1/en not_active Expired - Fee Related
- 1997-10-03 ES ES97942821T patent/ES2189978T3/es not_active Expired - Lifetime
-
1999
- 1999-03-20 BG BG103348A patent/BG103348A/xx unknown
- 1999-03-23 IS IS5009A patent/IS5009A/is unknown
- 1999-03-30 NO NO19991561A patent/NO312961B1/no not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
EP0934286A1 (en) | 1999-08-11 |
IS5009A (is) | 1999-03-23 |
EP0934286B1 (en) | 2003-01-08 |
EA001625B1 (ru) | 2001-06-25 |
CN1238766A (zh) | 1999-12-15 |
US6200999B1 (en) | 2001-03-13 |
DE69718338D1 (de) | 2003-02-13 |
BG103348A (en) | 1999-11-30 |
AU4451797A (en) | 1998-05-05 |
JP2001501630A (ja) | 2001-02-06 |
KR20000048908A (ko) | 2000-07-25 |
CZ116899A3 (cs) | 1999-09-15 |
TR199900724T2 (xx) | 1999-06-21 |
WO1998015542A1 (en) | 1998-04-16 |
HUP0000084A3 (en) | 2001-12-28 |
IL129135A0 (en) | 2000-02-17 |
NO991561D0 (no) | 1999-03-30 |
ATE230734T1 (de) | 2003-01-15 |
AR008880A1 (es) | 2000-02-23 |
HUP0000084A2 (hu) | 2000-06-28 |
EA199900358A1 (ru) | 1999-10-28 |
NO991561L (no) | 1999-06-04 |
UA52698C2 (uk) | 2003-01-15 |
BR9712198A (pt) | 1999-08-31 |
PL332553A1 (en) | 1999-09-13 |
ZA978877B (en) | 1998-04-17 |
SK42899A3 (en) | 1999-08-06 |
AU733004B2 (en) | 2001-05-03 |
CA2268028A1 (en) | 1998-04-16 |
ES2189978T3 (es) | 2003-07-16 |
NZ334798A (en) | 2000-06-23 |
DE69718338T2 (de) | 2003-10-16 |
CA2268028C (en) | 2003-03-18 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPH06507625A (ja) | アンギオテンシンiiアンタゴニストとしての酸官能基を有する置換ピリミジノン | |
NO312961B1 (no) | 3-alkoksyisoksazol-4-yl-substituerte 2- aminokarboksylsyreforbindelser | |
KR101009554B1 (ko) | Pde7 억제제로서 스피로시클릭 퀴나졸린 유도체 | |
JP2001520643A (ja) | エンドテリン介在障害治療用のスルホンアミド類 | |
HUE029485T2 (en) | New cyclohexylamine derivatives with B2 adrenergic agonist and M3 muscarinic antagonist activity | |
AU5676898A (en) | Atropisomers of 3-aryl-4(3h)-quinazolinones and their use as ampa-receptor antagonists | |
EP0884316B1 (en) | Quinazoline-4-one AMPA antagonists | |
US5591866A (en) | (1H-indol-1-yl)-2-(amino)acetamide derivatives and preparation thereof | |
RU2138488C1 (ru) | Соединения 2-аминокарбоновой кислоты, замещенной 5-арилизоксазол-4-илом, и фармацевтическая композиция на их основе | |
CA2647163C (en) | Modified macrophage migration inhibitory factor inhibitors | |
JPH08507303A (ja) | 非競合的nmda受容体アンタゴニストとしての2h−1,2,4−ベンゾチアジアジン3(4h)−オン1,1ジオキシド誘導体の使用 | |
CN108794517A (zh) | 一种精氨酸酶抑制剂及其制备方法与用途 | |
KR20000052876A (ko) | 아미노산 수용체의 결합 부위에 친화력을 갖는 벤족사졸 유도체 | |
CN115466251A (zh) | 一类稠杂环化合物、及其制法和药物组合物与用途 | |
JP2013519727A (ja) | 新規の5員複素環誘導体及びその製造方法 | |
JP2001509507A (ja) | 5−(3−フェニル−3−オキソ−プロピル)−1h−テトラゾール誘導体 | |
WO2018179343A1 (ja) | アダマンタン誘導体およびその医薬としての使用 | |
AU2003288077A1 (en) | Indol derivatives and their use as 5-ht ligands | |
HUT73170A (en) | Ureido-acetamide derivatives, preparation thereof and drugs containing same |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |