ZA200210004B - Substituted phthalides as anti-convulsive drugs. - Google Patents
Substituted phthalides as anti-convulsive drugs. Download PDFInfo
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- ZA200210004B ZA200210004B ZA200210004A ZA200210004A ZA200210004B ZA 200210004 B ZA200210004 B ZA 200210004B ZA 200210004 A ZA200210004 A ZA 200210004A ZA 200210004 A ZA200210004 A ZA 200210004A ZA 200210004 B ZA200210004 B ZA 200210004B
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- South Africa
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- compound
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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 description 108
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 18
- 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
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 238000000034 method Methods 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
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 5
- -1 hydroxy, carboxy Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 206010015037 epilepsy Diseases 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
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- DQBGVUCLKLYTJM-LLVKDONJSA-N (3r)-6-amino-3-butyl-3h-2-benzofuran-1-one Chemical compound NC1=CC=C2[C@@H](CCCC)OC(=O)C2=C1 DQBGVUCLKLYTJM-LLVKDONJSA-N 0.000 claims description 2
- 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 2
- 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 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
- 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 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
- 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 2
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 230000032683 aging Effects 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 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
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 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
- 125000002887 hydroxy group Chemical group [H]O* 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
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 206010010904 Convulsion Diseases 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-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
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 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
- HJXMNVQARNZTEE-UHFFFAOYSA-N Butylphthalide Chemical compound C1=CC=C2C(CCCC)OC(=O)C2=C1 HJXMNVQARNZTEE-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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 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
- 230000002411 adverse Effects 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 230000003556 anti-epileptic effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 230000000324 neuroprotective effect Effects 0.000 description 2
- JKNKNWJNCOJPLI-UHFFFAOYSA-N o-phthalaldehydic acid Chemical compound C1=CC=C2C(O)OC(=O)C2=C1 JKNKNWJNCOJPLI-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000009877 rendering Methods 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 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
- OBVFNDZOAJBXJM-UHFFFAOYSA-N 1,3-dimethyl-10-[2-(4-methylpiperazin-1-yl)acetyl]-5h-pyrazolo[3,4-c][1,5]benzodiazepin-4-one Chemical compound C1CN(C)CCN1CC(=O)N1C2=CC=CC=C2NC(=O)C2=C1C(C)=NN2C OBVFNDZOAJBXJM-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- DYNFCHNNOHNJFG-UHFFFAOYSA-N 2-formylbenzoic acid Chemical compound OC(=O)C1=CC=CC=C1C=O DYNFCHNNOHNJFG-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
- VMTZKGPXYYJUAR-UHFFFAOYSA-N 3-ethyl-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(CC)OC(=O)C2=C1 VMTZKGPXYYJUAR-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 208000006264 Korsakoff syndrome Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- VQASKUSHBVDKGU-UHFFFAOYSA-N Paramethadione Chemical compound CCC1(C)OC(=O)N(C)C1=O VQASKUSHBVDKGU-UHFFFAOYSA-N 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960002767 ethosuximide Drugs 0.000 description 1
- HAPOVYFOVVWLRS-UHFFFAOYSA-N ethosuximide Chemical compound CCC1(C)CC(=O)NC1=O HAPOVYFOVVWLRS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 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 description 1
- 238000012153 long-term therapy Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229960003274 paramethadione Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 229950004963 zolenzepine Drugs 0.000 description 1
Classifications
-
- 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
-
- 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)
- General Chemical & Material Sciences (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)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (1)
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200210004B true ZA200210004B (en) | 2003-12-10 |
Family
ID=4587601
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200210004A ZA200210004B (en) | 2000-06-28 | 2002-12-10 | Substituted phthalides as anti-convulsive drugs. |
Country Status (19)
| Country | Link |
|---|---|
| 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 |
|---|---|---|---|---|
| JP4804353B2 (ja) * | 2003-05-14 | 2011-11-02 | ディーエスエム アイピー アセッツ ビー．ブイ． | 糖尿病の治療及び予防のためのフタリド誘導体の使用 |
| 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 |
| JP2008502607A (ja) * | 2004-06-18 | 2008-01-31 | 石薬集団中奇制薬技術（石家庄）有限公司 | 痴呆の予防および治療におけるＬ−ｎ−ブチルフタリドの適用 |
| 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 |
| 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 |
| 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 |
| 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 |
| JPH02209861A (ja) * | 1988-05-06 | 1990-08-21 | Ono Pharmaceut Co Ltd | アミノ酸誘導体及び該誘導体を有効成分として含有するエンケファリナーゼ阻害剤 |
| 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
-
2001
- 2001-06-27 WO PCT/IB2001/001535 patent/WO2002000638A2/en not_active Application Discontinuation
- 2001-06-27 NZ NZ523174A patent/NZ523174A/en unknown
- 2001-06-27 EP EP01958282A patent/EP1320528A2/en not_active Withdrawn
- 2001-06-27 EA EA200300044A patent/EA200300044A1/ru unknown
- 2001-06-27 BR BR0112043-3A patent/BR0112043A/pt not_active IP Right Cessation
- 2001-06-27 KR KR1020027017839A patent/KR20030024710A/ko not_active Application Discontinuation
- 2001-06-27 CN CNB018120687A patent/CN100402515C/zh not_active Expired - Fee Related
- 2001-06-27 CA CA002413752A patent/CA2413752A1/en not_active Abandoned
- 2001-06-27 CZ CZ2003245A patent/CZ2003245A3/cs unknown
- 2001-06-27 HU HU0301567A patent/HUP0301567A3/hu unknown
- 2001-06-27 AR ARP010103051A patent/AR030239A1/es not_active Application Discontinuation
- 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 US US10/312,650 patent/US6689808B2/en not_active Expired - Fee Related
- 2001-06-27 AU AU2001280004A patent/AU2001280004A1/en not_active Abandoned
- 2001-06-27 JP JP2002505386A patent/JP2004501909A/ja active Pending
- 2001-06-27 MX MXPA02012569A patent/MXPA02012569A/es unknown
-
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 |
|---|---|
| EA200300044A1 (ru) | 2003-06-26 |
| PL359373A1 (en) | 2004-08-23 |
| SK1062003A3 (en) | 2003-05-02 |
| HUP0301567A3 (en) | 2005-08-29 |
| MXPA02012569A (es) | 2004-05-17 |
| EP1320528A2 (en) | 2003-06-25 |
| JP2004501909A (ja) | 2004-01-22 |
| CZ2003245A3 (cs) | 2003-05-14 |
| CA2413752A1 (en) | 2002-01-03 |
| WO2002000638A2 (en) | 2002-01-03 |
| CN1182127C (zh) | 2004-12-29 |
| WO2002000638A3 (en) | 2002-05-23 |
| NO20026154D0 (no) | 2002-12-20 |
| US6689808B2 (en) | 2004-02-10 |
| KR20030024710A (ko) | 2003-03-26 |
| NO20026154L (no) | 2003-02-20 |
| AR030239A1 (es) | 2003-08-13 |
| AU2001280004A1 (en) | 2002-01-08 |
| BR0112043A (pt) | 2003-10-28 |
| NZ523174A (en) | 2004-06-25 |
| WO2002000638A8 (en) | 2003-08-28 |
| CN100402515C (zh) | 2008-07-16 |
| CN1330069A (zh) | 2002-01-09 |
| CN1440398A (zh) | 2003-09-03 |
| US20030220393A1 (en) | 2003-11-27 |
| HUP0301567A2 (hu) | 2003-09-29 |
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