DE69530706T2 - Huperzin-derivate, ihre herstellung und ihre verwendung - Google Patents
Huperzin-derivate, ihre herstellung und ihre verwendung Download PDFInfo
- Publication number
- DE69530706T2 DE69530706T2 DE69530706T DE69530706T DE69530706T2 DE 69530706 T2 DE69530706 T2 DE 69530706T2 DE 69530706 T DE69530706 T DE 69530706T DE 69530706 T DE69530706 T DE 69530706T DE 69530706 T2 DE69530706 T2 DE 69530706T2
- Authority
- DE
- Germany
- Prior art keywords
- huperzine
- alkyl
- group
- derivative
- hydrogen
- Prior art date
- 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.)
- Expired - Fee Related
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 10
- ZQPQGKQTIZYFEF-WCVJEAGWSA-N Huperzine Natural products C1([C@H]2[C@H](O)C(=O)N[C@H]2[C@@H](O)C=2C=CC=CC=2)=CC=CC=C1 ZQPQGKQTIZYFEF-WCVJEAGWSA-N 0.000 title description 2
- ZRJBHWIHUMBLCN-YQEJDHNASA-N huperzine A Chemical class N1C(=O)C=CC2=C1C[C@H]1\C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-YQEJDHNASA-N 0.000 claims abstract description 35
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- -1 hydroxy, amino Chemical group 0.000 claims abstract description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
- 125000002541 furyl group Chemical group 0.000 claims abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical group 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- 125000005942 tetrahydropyridyl group Chemical group 0.000 claims abstract description 5
- 125000004925 dihydropyridyl group Chemical group N1(CC=CC=C1)* 0.000 claims abstract description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 18
- ZRJBHWIHUMBLCN-SEQYCRGISA-N Huperzine A Natural products N1C(=O)C=CC2=C1C[C@H]1/C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-SEQYCRGISA-N 0.000 claims description 11
- ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 claims description 11
- ZRJBHWIHUMBLCN-BMIGLBTASA-N rac-huperzine A Natural products N1C(=O)C=CC2=C1C[C@@H]1C(=CC)[C@@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-BMIGLBTASA-N 0.000 claims description 11
- 150000002431 hydrogen Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- 206010012289 Dementia Diseases 0.000 claims description 3
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 150000008065 acid anhydrides Chemical class 0.000 claims description 2
- 150000001263 acyl chlorides Chemical class 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 206010036631 Presenile dementia Diseases 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 239000000544 cholinesterase inhibitor Substances 0.000 abstract description 3
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 description 16
- 150000001875 compounds Chemical class 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 108090000371 Esterases Proteins 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 108090000790 Enzymes Proteins 0.000 description 7
- 102000004190 Enzymes Human genes 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 6
- 229960004373 acetylcholine Drugs 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229960001231 choline Drugs 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 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
- 229930013930 alkaloid Natural products 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000006993 memory improvement Effects 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102100032404 Cholinesterase Human genes 0.000 description 2
- 101710083761 Cholinesterase Proteins 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241001090156 Huperzia serrata Species 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 2
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 238000004737 colorimetric analysis Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 206010027175 memory impairment Diseases 0.000 description 2
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 2
- 229960002646 scopolamine Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- SMBBQHHYSLHDHF-UHFFFAOYSA-M 2-acetyloxyethyl(trimethyl)azanium;iodide Chemical compound [I-].CC(=O)OCC[N+](C)(C)C SMBBQHHYSLHDHF-UHFFFAOYSA-M 0.000 description 1
- GALNBQVDMJRFGJ-UHFFFAOYSA-M 2-butanoyloxyethyl(trimethyl)azanium;iodide Chemical compound [I-].CCCC(=O)OCC[N+](C)(C)C GALNBQVDMJRFGJ-UHFFFAOYSA-M 0.000 description 1
- FQRQWPNYJOFDLO-UHFFFAOYSA-N 2-hydroxy-4,6-dimethoxybenzaldehyde Chemical compound COC1=CC(O)=C(C=O)C(OC)=C1 FQRQWPNYJOFDLO-UHFFFAOYSA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- MJUHIAWSJRKXSH-UHFFFAOYSA-N 2-pyridin-3-ylacetaldehyde Chemical compound O=CCC1=CC=CN=C1 MJUHIAWSJRKXSH-UHFFFAOYSA-N 0.000 description 1
- HPOIPOPJGBKXIR-UHFFFAOYSA-N 3,6-dimethoxy-10-methyl-galantham-1-ene Natural products O1C(C(=CC=2)OC)=C3C=2CN(C)CCC23C1CC(OC)C=C2 HPOIPOPJGBKXIR-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 229940122601 Esterase inhibitor Drugs 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 238000012850 discrimination method Methods 0.000 description 1
- 210000003617 erythrocyte membrane Anatomy 0.000 description 1
- 239000002329 esterase inhibitor Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000009191 jumping Effects 0.000 description 1
- IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000018791 negative regulation of catalytic activity Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960001697 physostigmine Drugs 0.000 description 1
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular 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
- A61P25/28—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN94114057 | 1994-12-28 | ||
| CN94114057A CN1125725A (zh) | 1994-12-28 | 1994-12-28 | 一类海克林碱衍生物及它的用途 |
| PCT/CN1995/000100 WO1996020176A1 (fr) | 1994-12-28 | 1995-12-26 | Derives d'huperzine a, leur preparation et leur emploi |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69530706D1 DE69530706D1 (de) | 2003-06-12 |
| DE69530706T2 true DE69530706T2 (de) | 2004-03-25 |
Family
ID=5037011
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69530706T Expired - Fee Related DE69530706T2 (de) | 1994-12-28 | 1995-12-26 | Huperzin-derivate, ihre herstellung und ihre verwendung |
Country Status (11)
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100210590A1 (en) * | 1995-09-27 | 2010-08-19 | Northwestern University | Compositions and treatments for seizure-related disorders |
| NL1009437C2 (nl) * | 1998-06-18 | 1999-12-21 | Xenobiosis | Extractiewerkwijze. |
| EP1891954A3 (en) | 1998-09-30 | 2009-01-14 | Takeda Pharmaceutical Company Limited | Acetylcholinesterase inhibitors for improving excretory potency of urinary bladder |
| US6159986A (en) * | 1999-11-02 | 2000-12-12 | Altman; David A. | Compounds and therapy for resisting memory loss in humans |
| US6436972B1 (en) | 2000-04-10 | 2002-08-20 | Dalhousie University | Pyridones and their use as modulators of serine hydrolase enzymes |
| CA2408148A1 (en) * | 2000-05-05 | 2001-11-15 | United States Army Medical Research And Materiel Command | Assay for detecting, measuring and monitoring the activities and concentrations of proteins and methods of use thereof |
| US6369052B1 (en) | 2000-08-07 | 2002-04-09 | Georgetown University | Combination of huperzine and nicotinic compounds as a neuroprotective agent |
| KR100390777B1 (ko) * | 2000-12-19 | 2003-07-10 | 한국화학연구원 | 피리돈 유도체의 제조방법 |
| DE10144041B9 (de) * | 2001-09-07 | 2012-07-26 | Leica Mikrosysteme Gmbh | Gerät zum selbsttätigen Zuführen von Objektträgern zu einem Eindeckautomaten |
| CN100398093C (zh) * | 2003-03-14 | 2008-07-02 | 德比欧药物研究有限公司 | 皮下给药系统、其制备方法及其治疗胆碱能缺乏障碍的用途 |
| BRPI0407818A (pt) * | 2003-03-14 | 2006-02-14 | Debio Rech Pharma Sa | sistema de distribuição subcutánea, processo para a preparação do mesmo e uso do mesmo para o tratamento das doenças da deficiência colinérgica |
| CN1308312C (zh) * | 2003-11-13 | 2007-04-04 | 中国科学院上海药物研究所 | 石杉碱乙双分子和双功能团衍生物、制备方法及它的用途 |
| US20050222123A1 (en) | 2004-01-27 | 2005-10-06 | North Shore-Long Island Jewish Research Institute | Cholinesterase inhibitors for treating inflammation |
| WO2006050359A2 (en) * | 2004-11-02 | 2006-05-11 | Northwestern University | Pyridazine compounds and methods |
| EP3056200B1 (en) | 2005-05-23 | 2023-09-06 | President and Fellows of Harvard College | Huperzine for use in treating seizure |
| US20070179123A1 (en) * | 2005-11-08 | 2007-08-02 | Chiang Peter K | Methods and compositions for treating diseases associated with pathogenic proteins |
| CA2650711A1 (en) * | 2006-04-28 | 2007-11-08 | Northwestern University | Compositions and treatments using pyridazine compounds and cholinesterase inhibitors |
| US8097726B2 (en) * | 2006-05-17 | 2012-01-17 | Industrial Technology Research Institute | Huperzine a compound for treatment of alzheimer's disease |
| EP2044937A4 (en) * | 2006-07-05 | 2010-10-27 | Tianjin Hemay Bio Tech Co Ltd | ANALGESIC DERIVATIVES 5,9 - METHANOCYCLO OCTA (B) PYRIDINE - 2 (1H) - ONE, PROCESS FOR PREPARING SAME AND USE THEREOF |
| CN100528844C (zh) * | 2007-04-20 | 2009-08-19 | 中国科学院昆明植物研究所 | 石杉碱甲衍生物,其制备方法和其应用 |
| TWI404531B (zh) * | 2007-05-17 | 2013-08-11 | Ind Tech Res Inst | 石杉鹼甲化合物及包含此化合物之醫藥組合物 |
| WO2010028134A2 (en) * | 2008-09-04 | 2010-03-11 | President And Fellows Of Harvard College | Treatment of neurological disorders using huperzine |
| CN101797223B (zh) * | 2009-02-06 | 2012-05-23 | 上海交通大学医学院 | 石杉碱甲眼用制剂及其应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5177082A (en) * | 1985-11-05 | 1993-01-05 | Yu Chao Mei | Huperzines and analogs |
| US4968672A (en) * | 1987-01-02 | 1990-11-06 | The United States Of America As Represented By The Department Of Health And Human Services | Adenosine receptor prodrugs |
| US4929731A (en) * | 1989-02-21 | 1990-05-29 | University Of Pittsburgh | Method for the synthesis of huperzine A and analogs thereof and compounds useful therein |
| US5104880A (en) * | 1991-05-01 | 1992-04-14 | Mayo Foundation For Medical Education And Research | Huperzine a analogs as acetylcholinesterase inhibitors |
| US5684018A (en) * | 1994-12-13 | 1997-11-04 | Merck & Co., Inc. | Acyloxyisopropyl carbamates as prodrugs for amine drugs |
-
1994
- 1994-12-28 CN CN94114057A patent/CN1125725A/zh active Pending
-
1995
- 1995-12-26 PT PT95941572T patent/PT806416E/pt unknown
- 1995-12-26 AT AT95941572T patent/ATE239708T1/de not_active IP Right Cessation
- 1995-12-26 JP JP52010296A patent/JP3545416B2/ja not_active Expired - Fee Related
- 1995-12-26 ES ES95941572T patent/ES2199259T3/es not_active Expired - Lifetime
- 1995-12-26 AU AU42966/96A patent/AU4296696A/en not_active Abandoned
- 1995-12-26 WO PCT/CN1995/000100 patent/WO1996020176A1/zh active IP Right Grant
- 1995-12-26 US US08/860,524 patent/US5929084A/en not_active Ceased
- 1995-12-26 EP EP95941572A patent/EP0806416B1/en not_active Expired - Lifetime
- 1995-12-26 DE DE69530706T patent/DE69530706T2/de not_active Expired - Fee Related
- 1995-12-26 DK DK95941572T patent/DK0806416T3/da active
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2003
- 2003-05-26 JP JP2003148129A patent/JP4105592B2/ja not_active Expired - Fee Related
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2007
- 2007-07-02 JP JP2007174592A patent/JP2007246545A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| ES2199259T3 (es) | 2004-02-16 |
| DE69530706D1 (de) | 2003-06-12 |
| AU4296696A (en) | 1996-07-19 |
| PT806416E (pt) | 2003-09-30 |
| EP0806416A1 (en) | 1997-11-12 |
| JP2007246545A (ja) | 2007-09-27 |
| DK0806416T3 (da) | 2003-09-01 |
| CN1125725A (zh) | 1996-07-03 |
| JP4105592B2 (ja) | 2008-06-25 |
| US5929084A (en) | 1999-07-27 |
| WO1996020176A1 (fr) | 1996-07-04 |
| EP0806416B1 (en) | 2003-05-07 |
| ATE239708T1 (de) | 2003-05-15 |
| JPH10511651A (ja) | 1998-11-10 |
| JP3545416B2 (ja) | 2004-07-21 |
| JP2003306481A (ja) | 2003-10-28 |
| EP0806416A4 (en) | 1998-04-15 |
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