NO325764B1 - Benzoksazin-forbindelser for forandring av synaptisk respons - Google Patents

Benzoksazin-forbindelser for forandring av synaptisk respons Download PDF

Info

Publication number: NO325764B1
Authority: NO; Norway
Prior art keywords: compound; accordance; alkyl; compounds; fluoroalkyl
Prior art date: 1997-12-24

Application number

NO20003166A

Other languages

English (en)

Norwegian (no)

Other versions

NO20003166D0 (no

NO20003166L (no

Inventor

Gary A Rogers

Christopher M Marrs

Original Assignee

Univ California

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.)

1997-12-24

Filing date

2000-06-19

Publication date

2008-07-14

2000-06-19 Application filed by Univ California filed Critical Univ California

2000-06-19 Publication of NO20003166D0 publication Critical patent/NO20003166D0/no

2000-08-07 Publication of NO20003166L publication Critical patent/NO20003166L/no

2008-07-14 Publication of NO325764B1 publication Critical patent/NO325764B1/no

Links

230000009782 synaptic response Effects 0.000 title claims abstract description 8
150000005130 benzoxazines Chemical class 0.000 title description 7
230000008859 change Effects 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 120
108090000078 AMPA Receptors Proteins 0.000 claims abstract description 28
102000003678 AMPA Receptors Human genes 0.000 claims abstract description 27
238000000034 method Methods 0.000 claims abstract description 24
230000001404 mediated effect Effects 0.000 claims abstract description 10
125000003709 fluoroalkyl group Chemical group 0.000 claims description 26
-1 cyano, hydroxy Chemical group 0.000 claims description 21
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
125000004093 cyano group Chemical group *C#N 0.000 claims description 13
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 12
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
230000001965 increasing effect Effects 0.000 claims description 12
230000001149 cognitive effect Effects 0.000 claims description 10
125000003118 aryl group Chemical group 0.000 claims description 8
230000006399 behavior Effects 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
230000001953 sensory effect Effects 0.000 claims description 8
201000000980 schizophrenia Diseases 0.000 claims description 6
150000003573 thiols Chemical class 0.000 claims description 6
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 4
238000010828 elution Methods 0.000 claims description 4
125000004428 fluoroalkoxy group Chemical group 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
UZOWWWGTPXDAAB-UHFFFAOYSA-N 2,4,12,14-tetraoxa-7-azatetracyclo[7.7.0.03,7.011,15]hexadeca-1(16),5,9,11(15)-tetraen-8-one Chemical compound O1C2=CC=3OCOC=3C=C2C(=O)N2C1OC=C2 UZOWWWGTPXDAAB-UHFFFAOYSA-N 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 3
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
230000000698 schizophrenic effect Effects 0.000 claims description 3
230000001419 dependent effect Effects 0.000 claims description 2
230000009467 reduction Effects 0.000 claims description 2
239000000825 pharmaceutical preparation Substances 0.000 claims 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
125000001072 heteroaryl group Chemical group 0.000 claims 1
125000005114 heteroarylalkoxy group Chemical group 0.000 claims 1
238000005728 strengthening Methods 0.000 claims 1
210000004556 brain Anatomy 0.000 abstract description 14
210000000225 synapse Anatomy 0.000 abstract description 13
230000002964 excitative effect Effects 0.000 abstract description 9
230000002708 enhancing effect Effects 0.000 abstract description 5
CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical group C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 abstract description 4
239000002243 precursor Substances 0.000 abstract description 2
230000001771 impaired effect Effects 0.000 abstract 2
230000036992 cognitive tasks Effects 0.000 abstract 1
230000007812 deficiency Effects 0.000 abstract 1
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 26
QUTYKIXIUDQOLK-PRJMDXOYSA-N 5-O-(1-carboxyvinyl)-3-phosphoshikimic acid Chemical compound O[C@H]1[C@H](OC(=C)C(O)=O)CC(C(O)=O)=C[C@H]1OP(O)(O)=O QUTYKIXIUDQOLK-PRJMDXOYSA-N 0.000 description 24
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
230000000694 effects Effects 0.000 description 20
230000004044 response Effects 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
238000012360 testing method Methods 0.000 description 15
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 14
125000000217 alkyl group Chemical group 0.000 description 14
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
229940125904 compound 1 Drugs 0.000 description 12
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
239000007787 solid Substances 0.000 description 12
239000000243 solution Substances 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 11
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 11
229910052760 oxygen Inorganic materials 0.000 description 11
102000005962 receptors Human genes 0.000 description 11
108020003175 receptors Proteins 0.000 description 11
239000010409 thin film Substances 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
229940079593 drug Drugs 0.000 description 10
239000003814 drug Substances 0.000 description 10
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 10
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 9
210000001320 hippocampus Anatomy 0.000 description 9
239000000203 mixture Substances 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 9
238000006467 substitution reaction Methods 0.000 description 9
125000003545 alkoxy group Chemical group 0.000 description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 8
229910052799 carbon Inorganic materials 0.000 description 8
239000001301 oxygen Substances 0.000 description 8
230000000946 synaptic effect Effects 0.000 description 8
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 8
241000700159 Rattus Species 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
ZXNRTKGTQJPIJK-UHFFFAOYSA-N aniracetam Chemical compound C1=CC(OC)=CC=C1C(=O)N1C(=O)CCC1 ZXNRTKGTQJPIJK-UHFFFAOYSA-N 0.000 description 7
229960000793 aniracetam Drugs 0.000 description 7
125000004432 carbon atom Chemical group C* 0.000 description 7
239000001569 carbon dioxide Substances 0.000 description 7
229910002092 carbon dioxide Inorganic materials 0.000 description 7
230000027928 long-term synaptic potentiation Effects 0.000 description 7
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 7
229910052717 sulfur Inorganic materials 0.000 description 7
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
239000002775 capsule Substances 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
125000005842 heteroatom Chemical group 0.000 description 6
210000000653 nervous system Anatomy 0.000 description 6
230000010412 perfusion Effects 0.000 description 6
239000000047 product Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
ZTARHDAAHPNGMF-UHFFFAOYSA-N 6-hydroxy-1,3-benzodioxole-5-carboxylic acid Chemical compound C1=C(O)C(C(=O)O)=CC2=C1OCO2 ZTARHDAAHPNGMF-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
239000002253 acid Substances 0.000 description 5
150000001408 amides Chemical class 0.000 description 5
230000009286 beneficial effect Effects 0.000 description 5
230000004071 biological effect Effects 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
231100000673 dose–response relationship Toxicity 0.000 description 5
238000003818 flash chromatography Methods 0.000 description 5
238000009472 formulation Methods 0.000 description 5
230000006870 function Effects 0.000 description 5
125000004356 hydroxy functional group Chemical group O* 0.000 description 5
239000011593 sulfur Substances 0.000 description 5
101000768857 Arabidopsis thaliana 3-phosphoshikimate 1-carboxyvinyltransferase, chloroplastic Proteins 0.000 description 4
230000005526 G1 to G0 transition Effects 0.000 description 4
208000028017 Psychotic disease Diseases 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
230000008901 benefit Effects 0.000 description 4
125000004663 dialkyl amino group Chemical group 0.000 description 4
201000010099 disease Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
229910052731 fluorine Inorganic materials 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
230000000971 hippocampal effect Effects 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
230000036734 inhibitory postsynaptic potential Effects 0.000 description 4
239000000463 material Substances 0.000 description 4
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
230000001242 postsynaptic effect Effects 0.000 description 4
238000010791 quenching Methods 0.000 description 4
238000010992 reflux Methods 0.000 description 4
229960004889 salicylic acid Drugs 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
230000000638 stimulation Effects 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
UIOFUWFRIANQPC-JKIFEVAISA-N Floxacillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C1=C(C)ON=C1C1=C(F)C=CC=C1Cl UIOFUWFRIANQPC-JKIFEVAISA-N 0.000 description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
LUSZGTFNYDARNI-UHFFFAOYSA-N Sesamol Natural products OC1=CC=C2OCOC2=C1 LUSZGTFNYDARNI-UHFFFAOYSA-N 0.000 description 3
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000003342 alkenyl group Chemical group 0.000 description 3
125000000304 alkynyl group Chemical group 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229960003692 gamma aminobutyric acid Drugs 0.000 description 3
230000006872 improvement Effects 0.000 description 3
239000010410 layer Substances 0.000 description 3
230000014759 maintenance of location Effects 0.000 description 3
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125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
238000000746 purification Methods 0.000 description 3
239000000376 reactant Substances 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
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230000004936 stimulating effect Effects 0.000 description 3
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SBMAXSKHTYXTKD-UHFFFAOYSA-N 4-hydroxy-1,3-benzodioxole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2OCOC2=C1O SBMAXSKHTYXTKD-UHFFFAOYSA-N 0.000 description 2
IKCKXQPXYWBQSB-UHFFFAOYSA-N 6-hydroxy-2,3-dihydro-1,4-benzodioxine-7-carboxylic acid Chemical compound O1CCOC2=C1C=C(C(=O)O)C(O)=C2 IKCKXQPXYWBQSB-UHFFFAOYSA-N 0.000 description 2
BFMWEDBWKJDHSM-UHFFFAOYSA-N 6-hydroxy-n-(1-hydroxypropan-2-yl)-1,3-benzodioxole-5-carboxamide Chemical compound C1=C(O)C(C(=O)NC(CO)C)=CC2=C1OCO2 BFMWEDBWKJDHSM-UHFFFAOYSA-N 0.000 description 2
AWFBYYUTQBAEQR-UHFFFAOYSA-N 6-hydroxy-n-(2-hydroxypropyl)-1,3-benzodioxole-5-carboxamide Chemical compound C1=C(O)C(C(=O)NCC(O)C)=CC2=C1OCO2 AWFBYYUTQBAEQR-UHFFFAOYSA-N 0.000 description 2
DIAYOCALEBSCET-UHFFFAOYSA-N 6-hydroxy-n-(3-hydroxypropyl)-1,3-benzodioxole-5-carboxamide Chemical compound C1=C(O)C(C(=O)NCCCO)=CC2=C1OCO2 DIAYOCALEBSCET-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
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
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229910004298 SiO 2 Inorganic materials 0.000 description 2
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-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
230000004913 activation Effects 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 2
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125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
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210000001175 cerebrospinal fluid Anatomy 0.000 description 2
125000004122 cyclic group Chemical group 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
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BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
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VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
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UUDAMDVQRQNNHZ-UHFFFAOYSA-N (S)-AMPA Chemical compound CC=1ONC(=O)C=1CC(N)C(O)=O UUDAMDVQRQNNHZ-UHFFFAOYSA-N 0.000 description 1
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KDZFTYMGINYVLP-UHFFFAOYSA-N 2,2-dimethyl-1,3-benzodioxol-5-ol Chemical compound C1=C(O)C=C2OC(C)(C)OC2=C1 KDZFTYMGINYVLP-UHFFFAOYSA-N 0.000 description 1
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- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
- 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
- A61P25/18—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Epidemiology (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)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO20003166A 1997-12-24 2000-06-19 Benzoksazin-forbindelser for forandring av synaptisk respons NO325764B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/998,300 US5985871A (en)	1997-12-24	1997-12-24	Benzoxazine compounds for enhancing synaptic response
PCT/US1998/027027 WO1999033469A1 (en)	1997-12-24	1998-12-16	Benzoxazine compounds for enhancing synaptic response

Publications (3)

Publication Number	Publication Date
NO20003166D0 NO20003166D0 (no)	2000-06-19
NO20003166L NO20003166L (no)	2000-08-07
NO325764B1 true NO325764B1 (no)	2008-07-14

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NO20003166A NO325764B1 (no)	1997-12-24	2000-06-19	Benzoksazin-forbindelser for forandring av synaptisk respons

Country Status (22)

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US (1)	US5985871A (da)
EP (1)	EP1054673B1 (da)
JP (1)	JP4620244B2 (da)
KR (1)	KR100561049B1 (da)
CN (1)	CN1160360C (da)
AT (1)	ATE261306T1 (da)
AU (1)	AU746971B2 (da)
BR (1)	BR9814478A (da)
CA (1)	CA2316356C (da)
DE (1)	DE69822344T2 (da)
DK (1)	DK1054673T3 (da)
ES (1)	ES2217615T3 (da)
HU (1)	HUP0102056A3 (da)
IL (1)	IL136783A (da)
MX (1)	MXPA00006155A (da)
NO (1)	NO325764B1 (da)
NZ (1)	NZ505212A (da)
PL (1)	PL194905B1 (da)
PT (1)	PT1054673E (da)
RU (1)	RU2246497C2 (da)
TR (1)	TR200001971T2 (da)
WO (1)	WO1999033469A1 (da)

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US6110935A (en)	1997-02-13	2000-08-29	The Regents Of The University Of California	Benzofurazan compounds for enhancing glutamatergic synaptic responses
US6124278A (en) *	1998-04-03	2000-09-26	The Regents Of The University Of California	Acylbenzoxazines for enhancing synaptic response
DE10004572A1 (de) *	2000-02-02	2001-08-09	Boehringer Ingelheim Pharma	Neue positive allosterische AMPA-Rezeptor Modulatoren (PAARM), Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
TWI232863B (en) *	2001-06-11	2005-05-21	Akzo Nobel Nv	Benzoxazepine derivatives
NZ529671A (en)	2001-06-14	2005-10-28	Akzo Nobel Nv	(Pyrido/thieno)-[f]-oxazepin-5-one derivatives
EA200501117A1 (ru)	2003-01-13	2006-02-24	Кортекс Фармасеутикалс, Инк.	Способ лечения снижения когнитивной способности вследствие лишения сна и стресса
WO2006034196A1 (en) *	2004-09-17	2006-03-30	Lifelike Biomatic Inc.	Compositions for enhancing memory and methods therefor
PL2144506T3 (pl) *	2007-01-03	2012-04-30	Servier Lab	3-podstawiony-[1,2,3]-benzotriazynon jako związek do wzmacniania odpowiedzi glutaminianergicznych
EA200900937A1 (ru) *	2007-01-03	2009-12-30	Кортекс Фармасеутикалс, Инк.	Соединения 3-замещенного-[1,2,3]бензотриазинона для усиления глутаматергических синаптических ответов
KR101599661B1 (ko)	2007-05-17	2016-03-03	코텍스 파마슈티칼스, 인크.	글루타메이트에 의한 시냅스 반응을 향상시키기 위한 이치환된 아미드 화합물
US8119632B2 (en)	2007-08-10	2012-02-21	Cortex Pharmaceuticals, Inc.	Bicyclic amide derivatives for enhancing glutamatergic synaptic responses
BRPI0823262A2 (pt)	2007-08-10	2013-09-24	Cortex Pharma Inc	mÉtodo de tratamento de depressço respiratària e uso de um composto na fabricaÇço de um medicamento para o tratamento de depressço respiratària
US20110218190A1 (en) *	2008-11-10	2011-09-08	The Regents Of The University Of California	Therapeutic uses of ampa receptor modulators for treatment of motor dysfunction
WO2011109398A2 (en)	2010-03-02	2011-09-09	President And Fellows Of Harvard College	Methods and compositions for treatment of angelman syndrome and autism spectrum disorders
AU2012225784B2 (en)	2011-03-04	2016-03-17	The Regents Of The University Of California	Locally released growth factors to mediate motor recovery after stroke
SG193327A1 (en) *	2011-04-06	2013-10-30	Taiho Pharmaceutical Co Ltd	Novel imidazo-oxazine compound or salt thereof
AU2014277952A1 (en)	2013-06-13	2016-01-28	Veroscience Llc	Compositions and methods for treating metabolic disorders

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NZ255097A (en) *	1992-07-24	2001-04-27	Univ California	Heterocyclic derivatives (such as 1-(1,4-bgenzodioxan-5-ylcarbonyl)-1,2,3,6-tetrahydropyridine) and medicaments that enhance synaptic responses
JPH0943929A (ja) *	1995-05-19	1997-02-14	Matsushita Electric Ind Co Ltd	電子写真複写装置
US5650409A (en) *	1995-06-02	1997-07-22	Cortex Pharmaceuticals, Inc.	Benzoyl piperidines/pyrrolidines for enhancing synaptic response
US5736543A (en) *	1996-04-03	1998-04-07	The Regents Of The University Of California	Benzoxazines for enhancing synaptic response

1997
- 1997-12-24 US US08/998,300 patent/US5985871A/en not_active Expired - Fee Related
1998
- 1998-12-16 HU HU0102056A patent/HUP0102056A3/hu unknown
- 1998-12-16 KR KR1020007007128A patent/KR100561049B1/ko not_active IP Right Cessation
- 1998-12-16 PL PL341427A patent/PL194905B1/pl not_active IP Right Cessation
- 1998-12-16 PT PT98964112T patent/PT1054673E/pt unknown
- 1998-12-16 EP EP98964112A patent/EP1054673B1/en not_active Expired - Lifetime
- 1998-12-16 IL IL13678398A patent/IL136783A/xx not_active IP Right Cessation
- 1998-12-16 BR BR9814478-2A patent/BR9814478A/pt not_active Application Discontinuation
- 1998-12-16 AU AU19305/99A patent/AU746971B2/en not_active Ceased
- 1998-12-16 RU RU2000119735/04A patent/RU2246497C2/ru not_active IP Right Cessation
- 1998-12-16 CN CNB988125390A patent/CN1160360C/zh not_active Expired - Fee Related
- 1998-12-16 AT AT98964112T patent/ATE261306T1/de active
- 1998-12-16 WO PCT/US1998/027027 patent/WO1999033469A1/en not_active Application Discontinuation
- 1998-12-16 JP JP2000526226A patent/JP4620244B2/ja not_active Expired - Fee Related
- 1998-12-16 DK DK98964112T patent/DK1054673T3/da active
- 1998-12-16 ES ES98964112T patent/ES2217615T3/es not_active Expired - Lifetime
- 1998-12-16 TR TR2000/01971T patent/TR200001971T2/xx unknown
- 1998-12-16 CA CA002316356A patent/CA2316356C/en not_active Expired - Fee Related
- 1998-12-16 MX MXPA00006155A patent/MXPA00006155A/es not_active IP Right Cessation
- 1998-12-16 DE DE69822344T patent/DE69822344T2/de not_active Expired - Lifetime
2000
- 2000-06-16 NZ NZ505212A patent/NZ505212A/xx unknown
- 2000-06-19 NO NO20003166A patent/NO325764B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
KR20010033615A (ko)	2001-04-25
BR9814478A (pt)	2000-10-10
TR200001971T2 (tr)	2001-01-22
WO1999033469A1 (en)	1999-07-08
MXPA00006155A (es)	2002-04-24
CA2316356A1 (en)	1999-07-08
RU2246497C2 (ru)	2005-02-20
CN1283114A (zh)	2001-02-07
JP4620244B2 (ja)	2011-01-26
ES2217615T3 (es)	2004-11-01
NZ505212A (en)	2003-02-28
CN1160360C (zh)	2004-08-04
DE69822344T2 (de)	2005-02-17
NO20003166D0 (no)	2000-06-19
ATE261306T1 (de)	2004-03-15
EP1054673A1 (en)	2000-11-29
CA2316356C (en)	2009-11-03
PL341427A1 (en)	2001-04-09
HUP0102056A3 (en)	2003-03-28
DK1054673T3 (da)	2004-07-05
IL136783A (en)	2005-11-20
EP1054673A4 (en)	2001-07-18
PL194905B1 (pl)	2007-07-31
EP1054673B1 (en)	2004-03-10
NO20003166L (no)	2000-08-07
US5985871A (en)	1999-11-16
PT1054673E (pt)	2004-08-31
KR100561049B1 (ko)	2006-03-16
IL136783A0 (en)	2001-06-14
AU746971B2 (en)	2002-05-09
DE69822344D1 (de)	2004-04-15
JP2001527045A (ja)	2001-12-25
AU1930599A (en)	1999-07-19
HUP0102056A2 (hu)	2001-11-28

Legal Events

Date	Code	Title	Description
2012-07-23	MM1K	Lapsed by not paying the annual fees

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