CA2449189A1 - Naphtothiazine positive allosteric ampa receptor modulators (paarm) - Google Patents

Naphtothiazine positive allosteric ampa receptor modulators (paarm) Download PDF

Info

Publication number: CA2449189A1
Authority: CA; Canada
Prior art keywords: alkyl; nr6r7; different; halogen; halogen atoms
Prior art date: 2001-05-17
Legal status (The legal status 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 status listed.): Abandoned

Application number

CA002449189A

Other languages

English (en)

French (fr)

Inventor

Angelo Ceci

Klaus Klinder

Thomas Weiser

Karin Winter

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Boehringer Ingelheim Pharma GmbH and Co KG

Original Assignee

Individual

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.)

2001-05-17

Filing date

2002-05-15

Publication date

2002-12-19

2002-05-15 Application filed by Individual filed Critical Individual

2002-12-19 Publication of CA2449189A1 publication Critical patent/CA2449189A1/en

Status Abandoned legal-status Critical Current

Links

102000003678 AMPA Receptors Human genes 0.000 title abstract description 8
108090000078 AMPA Receptors Proteins 0.000 title abstract description 8
230000003281 allosteric effect Effects 0.000 title abstract description 5
238000000034 method Methods 0.000 claims abstract description 11
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
150000001875 compounds Chemical class 0.000 claims description 55
125000005843 halogen group Chemical group 0.000 claims description 36
229910052739 hydrogen Inorganic materials 0.000 claims description 27
239000001257 hydrogen Substances 0.000 claims description 27
229910052736 halogen Inorganic materials 0.000 claims description 26
150000002367 halogens Chemical class 0.000 claims description 26
150000003839 salts Chemical class 0.000 claims description 23
150000002431 hydrogen Chemical class 0.000 claims description 21
239000013543 active substance Substances 0.000 claims description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
-1 -SO2-NR6R7 Chemical group 0.000 claims description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
125000004093 cyano group Chemical group *C#N 0.000 claims description 13
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 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
239000000969 carrier Substances 0.000 claims description 6
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
206010008120 Cerebral ischaemia Diseases 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
206010012289 Dementia Diseases 0.000 claims description 3
208000026139 Memory disease Diseases 0.000 claims description 3
208000015122 neurodegenerative disease Diseases 0.000 claims description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
201000000980 schizophrenia Diseases 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 73
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 11
229910006069 SO3H Inorganic materials 0.000 claims 5
230000004770 neurodegeneration Effects 0.000 claims 2
230000002265 prevention Effects 0.000 claims 2
230000000324 neuroprotective effect Effects 0.000 claims 1
239000000825 pharmaceutical preparation Substances 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 25
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
239000000203 mixture Substances 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
239000000284 extract Substances 0.000 description 17
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
230000015572 biosynthetic process Effects 0.000 description 15
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
238000003786 synthesis reaction Methods 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
238000004587 chromatography analysis Methods 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
229910052938 sodium sulfate Inorganic materials 0.000 description 12
235000011152 sodium sulphate Nutrition 0.000 description 12
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 11
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 11
229910052731 fluorine Inorganic materials 0.000 description 11
239000011737 fluorine Substances 0.000 description 11
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
125000004432 carbon atom Chemical group C* 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
229910052801 chlorine Inorganic materials 0.000 description 9
239000005457 ice water Substances 0.000 description 9
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
238000001704 evaporation Methods 0.000 description 8
230000008020 evaporation Effects 0.000 description 8
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
229920002261 Corn starch Polymers 0.000 description 7
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 7
125000000217 alkyl group Chemical group 0.000 description 7
239000008101 lactose Substances 0.000 description 7
235000019359 magnesium stearate Nutrition 0.000 description 7
DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical class C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 7
BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
238000010992 reflux Methods 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000001117 sulphuric acid Substances 0.000 description 6
235000011149 sulphuric acid Nutrition 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
BHHQJJRGLTVYHF-UHFFFAOYSA-N 2-amino-2-naphthalen-1-ylsulfonylacetic acid Chemical class C1=CC=C2C(S(=O)(=O)C(C(O)=O)N)=CC=CC2=C1 BHHQJJRGLTVYHF-UHFFFAOYSA-N 0.000 description 5
229920002472 Starch Polymers 0.000 description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
229960001701 chloroform Drugs 0.000 description 5
238000010586 diagram Methods 0.000 description 5
229920000137 polyphosphoric acid Polymers 0.000 description 5
239000001267 polyvinylpyrrolidone Substances 0.000 description 5
229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
239000008107 starch Substances 0.000 description 5
235000019698 starch Nutrition 0.000 description 5
239000000454 talc Substances 0.000 description 5
235000012222 talc Nutrition 0.000 description 5
229910052623 talc Inorganic materials 0.000 description 5
SFCNHCQPKLXWBW-UHFFFAOYSA-N 2,3-dihydronaphtho[1,8-de][1,3]thiazine-1,1-dioxide Chemical compound C1=CC(S(=O)(=O)CN2)=C3C2=CC=CC3=C1 SFCNHCQPKLXWBW-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
235000019759 Maize starch Nutrition 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
229910052784 alkaline earth metal Inorganic materials 0.000 description 4
229910000147 aluminium phosphate Inorganic materials 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
239000003085 diluting agent Substances 0.000 description 4
230000000694 effects Effects 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 4
150000002790 naphthalenes Chemical class 0.000 description 4
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 4
238000002360 preparation method Methods 0.000 description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 description 3
GAGAICHLGQDUTL-UHFFFAOYSA-N 4h-thiazin-3-one Chemical compound O=C1CC=CSN1 GAGAICHLGQDUTL-UHFFFAOYSA-N 0.000 description 3
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 3
239000001828 Gelatine Substances 0.000 description 3
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical class NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
239000003513 alkali Substances 0.000 description 3
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 3
239000002775 capsule Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
239000013078 crystal Substances 0.000 description 3
229960004132 diethyl ether Drugs 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
238000001802 infusion Methods 0.000 description 3
238000002347 injection Methods 0.000 description 3
239000007924 injection Substances 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
238000002156 mixing Methods 0.000 description 3
ZFIFHAKCBWOSRN-UHFFFAOYSA-N naphthalene-1-sulfonamide Chemical class C1=CC=C2C(S(=O)(=O)N)=CC=CC2=C1 ZFIFHAKCBWOSRN-UHFFFAOYSA-N 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000012312 sodium hydride Substances 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical class OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
SCMTYCKLUSZRPQ-UHFFFAOYSA-N 5-acetamidonaphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(NC(=O)C)=CC=CC2=C1S(Cl)(=O)=O SCMTYCKLUSZRPQ-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-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
206010021143 Hypoxia Diseases 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
229930040373 Paraformaldehyde Natural products 0.000 description 2
208000028017 Psychotic disease Diseases 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
239000004141 Sodium laurylsulphate Substances 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000000654 additive Substances 0.000 description 2
239000000556 agonist Substances 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
229910000019 calcium carbonate Inorganic materials 0.000 description 2
239000001506 calcium phosphate Substances 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
230000002490 cerebral effect Effects 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
230000003111 delayed effect Effects 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
239000003995 emulsifying agent Substances 0.000 description 2
238000000605 extraction Methods 0.000 description 2
235000019264 food flavour enhancer Nutrition 0.000 description 2
238000009472 formulation Methods 0.000 description 2
230000006870 function Effects 0.000 description 2
239000008187 granular material Substances 0.000 description 2
150000004678 hydrides Chemical class 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
BMNHZXMZLUHLHU-UHFFFAOYSA-N n-[5-(methylsulfamoyl)naphthalen-1-yl]acetamide Chemical compound C1=CC=C2C(S(=O)(=O)NC)=CC=CC2=C1NC(C)=O BMNHZXMZLUHLHU-UHFFFAOYSA-N 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
229920002866 paraformaldehyde Polymers 0.000 description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000003755 preservative agent Substances 0.000 description 2
150000003141 primary amines Chemical class 0.000 description 2
239000000047 product Substances 0.000 description 2
235000015424 sodium Nutrition 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
239000007787 solid Substances 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
238000009492 tablet coating Methods 0.000 description 2
239000002700 tablet coating Substances 0.000 description 2
238000012360 testing method Methods 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
RAGSWDIQBBZLLL-UHFFFAOYSA-N 2-chloroethyl(diethyl)azanium;chloride Chemical compound Cl.CCN(CC)CCCl RAGSWDIQBBZLLL-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
VGPCCJBOHQGWLW-UHFFFAOYSA-N 5-acetamidonaphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(NC(=O)C)=CC=CC2=C1S(O)(=O)=O VGPCCJBOHQGWLW-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/02—1,2-Thiazines; Hydrogenated 1,2-thiazines
- 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
- A61P25/28—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
- 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

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Cardiology (AREA)
Psychiatry (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)

CA002449189A 2001-05-17 2002-05-15 Naphtothiazine positive allosteric ampa receptor modulators (paarm) Abandoned CA2449189A1 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE10123952.1		2001-05-17
DE10123952A DE10123952A1 (de)	2001-05-17	2001-05-17	Neue positive allosterische AMPA-Rezeptor Modulatoren (PAARM), Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel
PCT/EP2002/005338 WO2002100411A1 (en)	2001-05-17	2002-05-15	Naphtothiazine positive allosteric ampa receptor modulators (paarm)

Publications (1)

Publication Number	Publication Date
CA2449189A1 true CA2449189A1 (en)	2002-12-19

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ID=7685080

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002449189A Abandoned CA2449189A1 (en)	2001-05-17	2002-05-15	Naphtothiazine positive allosteric ampa receptor modulators (paarm)

Country Status (26)

Country	Link
EP (1)	EP1404340A1 (cs)
JP (1)	JP2004529980A (cs)
KR (1)	KR20040007572A (cs)
CN (1)	CN1533278A (cs)
AR (1)	AR036332A1 (cs)
BG (1)	BG108324A (cs)
BR (1)	BR0209796A (cs)
CA (1)	CA2449189A1 (cs)
CO (1)	CO5550460A2 (cs)
CZ (1)	CZ20033112A3 (cs)
DE (1)	DE10123952A1 (cs)
EA (1)	EA006608B1 (cs)
EC (1)	ECSP034852A (cs)
EE (1)	EE200300566A (cs)
HR (1)	HRP20030933A2 (cs)
HU (1)	HUP0401273A3 (cs)
IL (1)	IL158642A0 (cs)
MX (1)	MXPA03010373A (cs)
NO (1)	NO20035088D0 (cs)
NZ (1)	NZ530154A (cs)
PL (1)	PL364053A1 (cs)
SK (1)	SK14222003A3 (cs)
UY (1)	UY27290A1 (cs)
WO (1)	WO2002100411A1 (cs)
YU (1)	YU90403A (cs)
ZA (1)	ZA200308466B (cs)

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JP2010501597A (ja) *	2006-08-31	2010-01-21	ザガバナーズオブザユニバーシティーオブアルバータ	正のアロステリックａｍｐａ受容体モジュレーターを用いて呼吸抑制を阻害する方法
CN111518058B (zh) *	2020-05-29	2021-03-09	四川大学华西医院	一种噁噻嗪类化合物及其用途

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2001
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2002
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2003
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Publication number	Publication date
BR0209796A (pt)	2004-06-01
ZA200308466B (en)	2004-05-24
MXPA03010373A (es)	2004-03-16
KR20040007572A (ko)	2004-01-24
CO5550460A2 (es)	2005-08-31
YU90403A (sh)	2006-05-25
IL158642A0 (en)	2004-05-12
CN1533278A (zh)	2004-09-29
HUP0401273A2 (hu)	2004-10-28
PL364053A1 (en)	2004-12-13
CZ20033112A3 (en)	2004-03-17
UY27290A1 (es)	2002-12-31
NO20035088L (no)	2003-11-14
JP2004529980A (ja)	2004-09-30
NO20035088D0 (no)	2003-11-14
SK14222003A3 (sk)	2004-05-04
BG108324A (bg)	2004-12-30
HUP0401273A3 (en)	2006-11-28
AR036332A1 (es)	2004-09-01
DE10123952A1 (de)	2002-11-21
HRP20030933A2 (en)	2004-04-30
EA006608B1 (ru)	2006-02-24
ECSP034852A (es)	2003-12-24
WO2002100411A1 (en)	2002-12-19
EE200300566A (et)	2004-02-16
NZ530154A (en)	2005-09-30
EP1404340A1 (en)	2004-04-07
EA200301167A1 (ru)	2004-06-24

Legal Events

Date	Code	Title	Description
2007-05-15	FZDE	Discontinued

Publication	Publication Date	Title
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WO2007049532A1 (ja)	2007-05-03	アミノジヒドロチアジン誘導体
US20030199502A1 (en)	2003-10-23	Indoloquinazolinones
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US7026475B2 (en)	2006-04-11	Positive allosteric AMPA receptor modulators (PAARM), processes for preparing them, and their use as pharmaceutical compositions
WO1994013651A1 (de)	1994-06-23	Benzazepinon-derivate
CA2449189A1 (en)	2002-12-19	Naphtothiazine positive allosteric ampa receptor modulators (paarm)
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AU2002345759A1 (en)	2002-12-23	Naphtothiazine positive allosteric AMPA receptor modulators (PAARM)
AU762526B2 (en)	2003-06-26	Novel type condensed pyridazinone compounds
JP2967231B2 (ja)	1999-10-25	１，４―チアジン誘導体
KR19990021835A (ko)	1999-03-25	축합 벤조디아제피논 유도체 및 이의 의약 조성물
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WO2017149511A1 (en)	2017-09-08	Use of 2-oxo-2h-pyrrol-1(5h)-carboxamide derivatives as anti-hiv agents and process for the production thereof
JP2002519346A (ja)	2002-07-02	１−（ベンゾチアゾール−２−イル）−４−（１−フェニルメチル）ピペラジン：ドーパミン受容体サブタイプ特異リガンド
MXPA01007493A (en)	2002-03-26	Polycyclic thiazole-2-ylides amines, method for the production thereof and their utilization as medicaments