SK1062003A3 - Substituted phthalides as anti-convulsive drugs - Google Patents
Substituted phthalides as anti-convulsive drugs Download PDFInfo
- Publication number
- SK1062003A3 SK1062003A3 SK106-2003A SK1062003A SK1062003A3 SK 1062003 A3 SK1062003 A3 SK 1062003A3 SK 1062003 A SK1062003 A SK 1062003A SK 1062003 A3 SK1062003 A3 SK 1062003A3
- Authority
- SK
- Slovakia
- Prior art keywords
- formula
- compound
- compounds
- defined above
- pharmaceutically acceptable
- Prior art date
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- 239000001961 anticonvulsive agent Substances 0.000 title description 4
- 125000005506 phthalide group Chemical group 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 191
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims abstract description 3
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 17
- 230000009471 action Effects 0.000 claims description 12
- 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 11
- 238000000034 method Methods 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- -1 hydroxy, carboxy Chemical group 0.000 claims description 7
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 206010008118 cerebral infarction Diseases 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 239000007858 starting material Substances 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- 201000006474 Brain Ischemia Diseases 0.000 claims description 4
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 4
- 230000004770 neurodegeneration Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- BWXSXZAIQQSFPW-UHFFFAOYSA-N 3,3-diethyl-6-nitro-2-benzofuran-1-one Chemical compound [O-][N+](=O)C1=CC=C2C(CC)(CC)OC(=O)C2=C1 BWXSXZAIQQSFPW-UHFFFAOYSA-N 0.000 claims description 3
- ASKLDELUMSEZPN-UHFFFAOYSA-N 3-butyl-6-(propan-2-ylamino)-3h-2-benzofuran-1-one Chemical compound CC(C)NC1=CC=C2C(CCCC)OC(=O)C2=C1 ASKLDELUMSEZPN-UHFFFAOYSA-N 0.000 claims description 3
- SWPWEPMPORVAHF-UHFFFAOYSA-N 6-amino-3,3-diethyl-2-benzofuran-1-one Chemical compound NC1=CC=C2C(CC)(CC)OC(=O)C2=C1 SWPWEPMPORVAHF-UHFFFAOYSA-N 0.000 claims description 3
- DQBGVUCLKLYTJM-UHFFFAOYSA-N 6-amino-3-butyl-3h-2-benzofuran-1-one Chemical compound NC1=CC=C2C(CCCC)OC(=O)C2=C1 DQBGVUCLKLYTJM-UHFFFAOYSA-N 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000006621 (C3-C8) cycloalkyl-(C1-C6) alkyl group Chemical group 0.000 claims description 2
- KQJFKERLWABNGU-UHFFFAOYSA-N 6-(dimethylamino)-3,3-dimethyl-2-benzofuran-1-one Chemical compound CN(C)C1=CC=C2C(C)(C)OC(=O)C2=C1 KQJFKERLWABNGU-UHFFFAOYSA-N 0.000 claims description 2
- YYDFTFDFORIGIP-UHFFFAOYSA-N 6-amino-3,3-dimethyl-2-benzofuran-1-one Chemical compound NC1=CC=C2C(C)(C)OC(=O)C2=C1 YYDFTFDFORIGIP-UHFFFAOYSA-N 0.000 claims description 2
- 208000024827 Alzheimer disease Diseases 0.000 claims description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 2
- 208000006264 Korsakoff syndrome Diseases 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 230000001149 cognitive effect Effects 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
- 230000007812 deficiency Effects 0.000 claims description 2
- 238000007336 electrophilic substitution reaction Methods 0.000 claims description 2
- 210000001652 frontal lobe Anatomy 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 claims description 2
- 230000015654 memory Effects 0.000 claims description 2
- GHOQWPSAWQMDAI-UHFFFAOYSA-N n-(1-butyl-3-oxo-1h-2-benzofuran-5-yl)formamide Chemical compound O=CNC1=CC=C2C(CCCC)OC(=O)C2=C1 GHOQWPSAWQMDAI-UHFFFAOYSA-N 0.000 claims description 2
- 238000006396 nitration reaction Methods 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 230000002739 subcortical effect Effects 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 70
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000004452 microanalysis Methods 0.000 description 30
- 239000000243 solution Substances 0.000 description 28
- 238000002844 melting Methods 0.000 description 25
- 230000008018 melting Effects 0.000 description 25
- 239000000203 mixture Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 239000000543 intermediate Substances 0.000 description 19
- 241000700159 Rattus Species 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 239000013078 crystal Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- 239000011777 magnesium Substances 0.000 description 7
- 229910052749 magnesium Inorganic materials 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 206010010904 Convulsion Diseases 0.000 description 5
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 229930195712 glutamate Natural products 0.000 description 5
- 230000000366 juvenile effect Effects 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 208000028867 ischemia Diseases 0.000 description 4
- 210000004129 prosencephalon Anatomy 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000007818 Grignard reagent Substances 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 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 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 3
- 150000008064 anhydrides Chemical class 0.000 description 3
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 3
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 150000004795 grignard reagents Chemical class 0.000 description 3
- 230000000324 neuroprotective effect Effects 0.000 description 3
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- 239000003208 petroleum Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 2
- DYNFCHNNOHNJFG-UHFFFAOYSA-N 2-formylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C=O DYNFCHNNOHNJFG-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- HJXMNVQARNZTEE-UHFFFAOYSA-N Butylphthalide Chemical compound C1=CC=C2C(CCCC)OC(=O)C2=C1 HJXMNVQARNZTEE-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 238000011785 NMRI mouse Methods 0.000 description 2
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001263 acyl chlorides Chemical class 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 230000003556 anti-epileptic effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
- 230000037411 cognitive enhancing Effects 0.000 description 2
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- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
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- 230000007246 mechanism Effects 0.000 description 2
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- JKNKNWJNCOJPLI-UHFFFAOYSA-N o-phthalaldehydic acid Chemical compound C1=CC=C2C(O)OC(=O)C2=C1 JKNKNWJNCOJPLI-UHFFFAOYSA-N 0.000 description 2
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- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
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- CNDHHGUSRIZDSL-UHFFFAOYSA-N 1-chlorooctane Chemical compound CCCCCCCCCl CNDHHGUSRIZDSL-UHFFFAOYSA-N 0.000 description 1
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- YEXOWHQZWLCHHD-UHFFFAOYSA-N 3,5-ditert-butyl-4-hydroxybenzoic acid Chemical compound CC(C)(C)C1=CC(C(O)=O)=CC(C(C)(C)C)=C1O YEXOWHQZWLCHHD-UHFFFAOYSA-N 0.000 description 1
- YZAZUDQLKAEAAT-UHFFFAOYSA-N 3-butyl-6-(cyclohexylamino)-3h-2-benzofuran-1-one Chemical compound C=1C=C2C(CCCC)OC(=O)C2=CC=1NC1CCCCC1 YZAZUDQLKAEAAT-UHFFFAOYSA-N 0.000 description 1
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- XHNYDLAEWCJRFU-UHFFFAOYSA-N n-(1-hexyl-3-oxo-1h-2-benzofuran-5-yl)acetamide Chemical compound CC(=O)NC1=CC=C2C(CCCCCC)OC(=O)C2=C1 XHNYDLAEWCJRFU-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Psychology (AREA)
- Psychiatry (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Indole Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB001193295A CN1182127C (zh) | 2000-06-28 | 2000-06-28 | 新的取代的2-苯并[c]呋喃酮化合物,其制备方法以及包含它们的药物组合物 |
| PCT/IB2001/001535 WO2002000638A2 (en) | 2000-06-28 | 2001-06-27 | Substituted phthalides as anti-convulsive drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK1062003A3 true SK1062003A3 (en) | 2003-05-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK106-2003A SK1062003A3 (en) | 2000-06-28 | 2001-06-27 | Substituted phthalides as anti-convulsive drugs |
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|---|---|
| US (1) | US6689808B2 (zh) |
| EP (1) | EP1320528A2 (zh) |
| JP (1) | JP2004501909A (zh) |
| KR (1) | KR20030024710A (zh) |
| CN (2) | CN1182127C (zh) |
| AR (1) | AR030239A1 (zh) |
| AU (1) | AU2001280004A1 (zh) |
| BR (1) | BR0112043A (zh) |
| CA (1) | CA2413752A1 (zh) |
| CZ (1) | CZ2003245A3 (zh) |
| EA (1) | EA200300044A1 (zh) |
| HU (1) | HUP0301567A3 (zh) |
| MX (1) | MXPA02012569A (zh) |
| NO (1) | NO20026154L (zh) |
| NZ (1) | NZ523174A (zh) |
| PL (1) | PL359373A1 (zh) |
| SK (1) | SK1062003A3 (zh) |
| WO (1) | WO2002000638A2 (zh) |
| ZA (1) | ZA200210004B (zh) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070082947A1 (en) | 2003-05-14 | 2007-04-12 | D Orazio Daniel | Use of phthalide derivatives for the treatment and prevention of diabetes mellitus |
| EP1662906A1 (en) | 2003-09-23 | 2006-06-07 | DSM IP Assets B.V. | Compositions for the treatment and prevention of diabetes mellitus |
| CN1605336A (zh) | 2003-10-10 | 2005-04-13 | 中国医学科学院药物研究所 | 左旋丁基苯酞在制备预防和治疗脑梗塞的药物中的应用 |
| US8552058B2 (en) * | 2004-06-18 | 2013-10-08 | CSPC Zhongqi Pharmaceutical Technology (Shijazhuang) Co., Ltd. | Application of L-n-butylphthalide in preventing and treating dementia |
| CN106074497A (zh) * | 2010-01-13 | 2016-11-09 | 石药集团恩必普药业有限公司 | 丁苯酞及其衍生物在制备治疗帕金森病的药物中的应用 |
| CN102260233A (zh) * | 2011-05-04 | 2011-11-30 | 武汉科技大学 | 3-丁基-1(3h)-异苯并呋喃酮衍生物及其制备方法 |
| CN105367526B (zh) * | 2015-10-14 | 2017-07-28 | 济南诚汇双达化工有限公司 | 一种高纯度正丁基苯酞的制备方法 |
| CN108727352B (zh) * | 2017-04-14 | 2021-04-23 | 四川大学 | 一类哌啶烷氨甲酰基苯酞类化合物、其制备方法和用途 |
| PL3845524T3 (pl) * | 2018-03-19 | 2022-10-24 | Henan Genuine Biotech Co., Ltd. | Związki kwasu benzoesowego i sposób ich wytwarzania oraz ich zastosowania |
| CN108752300B (zh) * | 2018-05-16 | 2022-03-25 | 中国科学院昆明植物研究所 | 苄烯叉苯肽类化合物及其药物组合物和其应用 |
| CN109111415B (zh) * | 2018-10-25 | 2022-08-23 | 安徽中医药大学 | 一类石斛生物碱衍生物、制备方法和医药用途 |
| CN112010837B (zh) * | 2019-05-28 | 2021-12-17 | 四川大学 | 一类吡啶甲胺基苯酞类化合物、其制备方法和用途 |
| CN112010827A (zh) * | 2019-05-28 | 2020-12-01 | 四川大学 | 一类苄胺基苯酞类化合物、其制备方法和用途 |
| CN110452203B (zh) * | 2019-08-29 | 2021-04-13 | 忻州师范学院 | 一种1-氧代-1,3-二氢-3-羟基苯并呋喃-5-甲酸的制备方法 |
| CN112794831B (zh) * | 2021-04-06 | 2021-07-27 | 北京理工大学 | 3-(3′-羟基丁基)异苯并呋喃-1(3h)-酮衍生物及其组合物、制备方法和用途 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1183053B (it) * | 1984-02-02 | 1987-10-05 | Farmaceutico Ct Lab | Derivati dell'alfa-amino-gamma-butirrolatton e, metodo per prepararli e composizioni farmaceutiche che li contengono |
| DE3615157A1 (de) * | 1986-05-05 | 1987-11-12 | Schwabe Willmar Gmbh & Co | 5-arylalkyl-4-alkoxy-2(5h)-furanone, zwischenprodukte und verfahren zu ihrer herstellung sowie ihre anwendung als therapeutische wirkstoffe |
| CA1330613C (en) * | 1988-05-06 | 1994-07-05 | Masanori Kawamura | Amino acid derivatives |
| TW270133B (zh) * | 1993-09-17 | 1996-02-11 | Ciba Geigy | |
| DE19618854A1 (de) * | 1996-05-10 | 1997-11-13 | Basf Ag | Verfahren zur Herstellung von Phthaliden |
| DE19626659A1 (de) * | 1996-07-03 | 1998-01-08 | Basf Ag | Verfahren zur Herstellung von Phthaliden |
-
2000
- 2000-06-28 CN CNB001193295A patent/CN1182127C/zh not_active Expired - Fee Related
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2001
- 2001-06-27 CZ CZ2003245A patent/CZ2003245A3/cs unknown
- 2001-06-27 AU AU2001280004A patent/AU2001280004A1/en not_active Abandoned
- 2001-06-27 EA EA200300044A patent/EA200300044A1/ru unknown
- 2001-06-27 KR KR1020027017839A patent/KR20030024710A/ko not_active Ceased
- 2001-06-27 BR BR0112043-3A patent/BR0112043A/pt not_active IP Right Cessation
- 2001-06-27 CA CA002413752A patent/CA2413752A1/en not_active Abandoned
- 2001-06-27 PL PL01359373A patent/PL359373A1/xx not_active Application Discontinuation
- 2001-06-27 SK SK106-2003A patent/SK1062003A3/sk unknown
- 2001-06-27 NZ NZ523174A patent/NZ523174A/en unknown
- 2001-06-27 US US10/312,650 patent/US6689808B2/en not_active Expired - Fee Related
- 2001-06-27 HU HU0301567A patent/HUP0301567A3/hu unknown
- 2001-06-27 CN CNB018120687A patent/CN100402515C/zh not_active Expired - Fee Related
- 2001-06-27 JP JP2002505386A patent/JP2004501909A/ja active Pending
- 2001-06-27 EP EP01958282A patent/EP1320528A2/en not_active Withdrawn
- 2001-06-27 MX MXPA02012569A patent/MXPA02012569A/es unknown
- 2001-06-27 WO PCT/IB2001/001535 patent/WO2002000638A2/en not_active Application Discontinuation
- 2001-06-27 AR ARP010103051A patent/AR030239A1/es not_active Application Discontinuation
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2002
- 2002-12-10 ZA ZA200210004A patent/ZA200210004B/en unknown
- 2002-12-20 NO NO20026154A patent/NO20026154L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NZ523174A (en) | 2004-06-25 |
| US20030220393A1 (en) | 2003-11-27 |
| JP2004501909A (ja) | 2004-01-22 |
| BR0112043A (pt) | 2003-10-28 |
| CN1182127C (zh) | 2004-12-29 |
| CN100402515C (zh) | 2008-07-16 |
| CN1330069A (zh) | 2002-01-09 |
| WO2002000638A3 (en) | 2002-05-23 |
| CA2413752A1 (en) | 2002-01-03 |
| AU2001280004A1 (en) | 2002-01-08 |
| NO20026154D0 (no) | 2002-12-20 |
| US6689808B2 (en) | 2004-02-10 |
| EA200300044A1 (ru) | 2003-06-26 |
| NO20026154L (no) | 2003-02-20 |
| MXPA02012569A (es) | 2004-05-17 |
| ZA200210004B (en) | 2003-12-10 |
| CN1440398A (zh) | 2003-09-03 |
| CZ2003245A3 (cs) | 2003-05-14 |
| PL359373A1 (en) | 2004-08-23 |
| WO2002000638A2 (en) | 2002-01-03 |
| EP1320528A2 (en) | 2003-06-25 |
| HUP0301567A3 (en) | 2005-08-29 |
| KR20030024710A (ko) | 2003-03-26 |
| WO2002000638A8 (en) | 2003-08-28 |
| HUP0301567A2 (hu) | 2003-09-29 |
| AR030239A1 (es) | 2003-08-13 |
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