NO312961B1 - 3-alkoksyisoksazol-4-yl-substituerte 2- aminokarboksylsyreforbindelser - Google Patents

3-alkoksyisoksazol-4-yl-substituerte 2- aminokarboksylsyreforbindelser Download PDF

Info

Publication number: NO312961B1
Authority: NO; Norway
Prior art keywords: group; alkyl; hydrogen; amino; mmol
Prior art date: 1996-10-04

Application number

NO19991561A

Other languages

English (en)

Norwegian (no)

Other versions

NO991561D0 (no

NO991561L (no

Inventor

Benny Bang-Andersen

Klaus Peter Boegesoe

Povl Krogsgaard-Larsen

Sibylle Moltzen Lenz

Original Assignee

Lundbeck & Co As H

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.)

1996-10-04

Filing date

1999-03-30

Publication date

2002-07-22

1999-03-30 Application filed by Lundbeck & Co As H filed Critical Lundbeck & Co As H

1999-03-30 Publication of NO991561D0 publication Critical patent/NO991561D0/no

1999-06-04 Publication of NO991561L publication Critical patent/NO991561L/no

2002-07-22 Publication of NO312961B1 publication Critical patent/NO312961B1/no

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
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230000003492 excitotoxic effect Effects 0.000 description 2
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
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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
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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
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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

NO19991561A 1996-10-04 1999-03-30 3-alkoksyisoksazol-4-yl-substituerte 2- aminokarboksylsyreforbindelser NO312961B1 (no)

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 (de)
EP (1)	EP0934286B1 (de)
JP (1)	JP2001501630A (de)
KR (1)	KR20000048908A (de)
CN (1)	CN1238766A (de)
AR (1)	AR008880A1 (de)
AT (1)	ATE230734T1 (de)
AU (1)	AU733004B2 (de)
BG (1)	BG103348A (de)
BR (1)	BR9712198A (de)
CA (1)	CA2268028C (de)
CZ (1)	CZ116899A3 (de)
DE (1)	DE69718338T2 (de)
EA (1)	EA001625B1 (de)
ES (1)	ES2189978T3 (de)
HU (1)	HUP0000084A3 (de)
IL (1)	IL129135A0 (de)
IS (1)	IS5009A (de)
NO (1)	NO312961B1 (de)
NZ (1)	NZ334798A (de)
PL (1)	PL332553A1 (de)
SK (1)	SK42899A3 (de)
TR (1)	TR199900724T2 (de)
UA (1)	UA52698C2 (de)
WO (1)	WO1998015542A1 (de)
ZA (1)	ZA978877B (de)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UA73749C2 (en) *	1999-11-01	2005-09-15		Diarylenines
HUP0302991A3 (en)	2000-09-15	2009-10-28	Vertex Pharma	Isoxazoles and their use as inhibitors of erk and pharmaceutical compositions containing the compounds
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
CA2521313A1 (en)	2003-04-09	2004-10-28	Wyeth	Derivatives of 2-(8,9-dioxo-2,6-diazabicyclo(5.2.o)non-1(7)-3n-2-yl)-al kyl phosphonic acid and their use as n-methyl-d-aspartate (nmda) recetor 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
WO2007042420A1 (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 (de)	2009-12-24	2011-06-29	Universidad del Pais Vasco	Verfahren und Zusammensetzung zur Behandlung von 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
RU2702121C1 (ru) *	2016-01-21	2019-10-04	Агро-Канесо Ко., Лтд.	Способ получения производного бензилового эфира 2-аминоникотиновой кислоты

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE69102816T2 (de)	1990-05-11	1995-03-16	Sankyo Co	Piperdinyloxy- und Chinindidinyloxy- isoxazol- Derivate, ihre Herstellung und ihre therapeutische Verwendung.
EP0665833B1 (de)	1992-10-23	1999-07-14	MERCK SHARP & DOHME LTD.	Dopamin rezeptor subtyp liganden
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 US US09/269,356 patent/US6200999B1/en not_active Expired - Fee Related
- 1997-10-03 EP EP97942821A patent/EP0934286B1/de not_active Expired - Lifetime
- 1997-10-03 KR KR1019990702938A patent/KR20000048908A/ko not_active Application Discontinuation
- 1997-10-03 AT AT97942821T patent/ATE230734T1/de not_active IP Right Cessation
- 1997-10-03 PL PL97332553A patent/PL332553A1/xx unknown
- 1997-10-03 IL IL12913597A patent/IL129135A0/xx unknown
- 1997-10-03 EA EA199900358A patent/EA001625B1/ru not_active IP Right Cessation
- 1997-10-03 ZA ZA9708877A patent/ZA978877B/xx unknown
- 1997-10-03 DE DE69718338T patent/DE69718338T2/de not_active Expired - Fee Related
- 1997-10-03 CN CN97180167A patent/CN1238766A/zh active Pending
- 1997-10-03 HU HU0000084A patent/HUP0000084A3/hu unknown
- 1997-10-03 WO PCT/DK1997/000426 patent/WO1998015542A1/en not_active Application Discontinuation
- 1997-10-03 CZ CZ991168A patent/CZ116899A3/cs unknown
- 1997-10-03 AU AU44517/97A patent/AU733004B2/en not_active Ceased
- 1997-10-03 NZ NZ334798A patent/NZ334798A/en unknown
- 1997-10-03 JP JP10517096A patent/JP2001501630A/ja active Pending
- 1997-10-03 BR BR9712198-3A patent/BR9712198A/pt unknown
- 1997-10-03 SK SK428-99A patent/SK42899A3/sk unknown
- 1997-10-03 ES ES97942821T patent/ES2189978T3/es not_active Expired - Lifetime
- 1997-10-03 TR TR1999/00724T patent/TR199900724T2/xx unknown
- 1997-10-03 CA CA002268028A patent/CA2268028C/en not_active Expired - Fee Related
- 1997-10-03 AR ARP970104586A patent/AR008880A1/es not_active Application Discontinuation
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
KR20000048908A (ko)	2000-07-25
AU733004B2 (en)	2001-05-03
BG103348A (en)	1999-11-30
CN1238766A (zh)	1999-12-15
BR9712198A (pt)	1999-08-31
ES2189978T3 (es)	2003-07-16
WO1998015542A1 (en)	1998-04-16
AR008880A1 (es)	2000-02-23
TR199900724T2 (xx)	1999-06-21
DE69718338T2 (de)	2003-10-16
AU4451797A (en)	1998-05-05
UA52698C2 (uk)	2003-01-15
CA2268028A1 (en)	1998-04-16
ATE230734T1 (de)	2003-01-15
JP2001501630A (ja)	2001-02-06
US6200999B1 (en)	2001-03-13
EP0934286A1 (de)	1999-08-11
EA199900358A1 (ru)	1999-10-28
IS5009A (is)	1999-03-23
CA2268028C (en)	2003-03-18
NZ334798A (en)	2000-06-23
ZA978877B (en)	1998-04-17
NO991561D0 (no)	1999-03-30
IL129135A0 (en)	2000-02-17
SK42899A3 (en)	1999-08-06
DE69718338D1 (de)	2003-02-13
EP0934286B1 (de)	2003-01-08
EA001625B1 (ru)	2001-06-25
PL332553A1 (en)	1999-09-13
HUP0000084A2 (hu)	2000-06-28
CZ116899A3 (cs)	1999-09-15
HUP0000084A3 (en)	2001-12-28
NO991561L (no)	1999-06-04

Legal Events

Date	Code	Title	Description
2004-10-18	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
JPH06507625A (ja)	1994-09-01	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)	2002-07-22	3-alkoksyisoksazol-4-yl-substituerte 2- aminokarboksylsyreforbindelser
KR101009554B1 (ko)	2011-01-18	Ｐｄｅ７ 억제제로서 스피로시클릭 퀴나졸린 유도체
JP2001520643A (ja)	2001-10-30	エンドテリン介在障害治療用のスルホンアミド類
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EP0884316B1 (de)	2002-09-04	Quinazolin-4-on AMPA Antagonisten
RU2138488C1 (ru)	1999-09-27	Соединения 2-аминокарбоновой кислоты, замещенной 5-арилизоксазол-4-илом, и фармацевтическая композиция на их основе
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JP2013519727A (ja)	2013-05-30	新規の５員複素環誘導体及びその製造方法
JP2001509507A (ja)	2001-07-24	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)	2018-10-04	アダマンタン誘導体およびその医薬としての使用
JP2837318B2 (ja)	1998-12-16	アンジオテンシンｉｉ拮抗性ピリジン誘導体
AU2003288077A1 (en)	2004-06-30	Indol derivatives and their use as 5-ht ligands
HUT73170A (en)	1996-06-28	Ureido-acetamide derivatives, preparation thereof and drugs containing same