IL124097A - History of trans-avincaminic acid esters, their preparation, pharmaceutical preparations containing them and their use as medicines - Google Patents
History of trans-avincaminic acid esters, their preparation, pharmaceutical preparations containing them and their use as medicinesInfo
- Publication number
- IL124097A IL124097A IL12409796A IL12409796A IL124097A IL 124097 A IL124097 A IL 124097A IL 12409796 A IL12409796 A IL 12409796A IL 12409796 A IL12409796 A IL 12409796A IL 124097 A IL124097 A IL 124097A
- Authority
- IL
- Israel
- Prior art keywords
- formula
- preparation
- trans
- compound
- therapeutically acceptable
- Prior art date
Links
- -1 apovincaminic acid ester Chemical class 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims description 32
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 239000003814 drug Substances 0.000 title claims description 4
- 229940079593 drug Drugs 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 4
- 150000001875 compounds Chemical class 0.000 claims description 88
- 230000003859 lipid peroxidation Effects 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 17
- 239000000203 mixture Substances 0.000 claims description 17
- 150000002148 esters Chemical class 0.000 claims description 15
- 208000028867 ischemia Diseases 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 208000000044 Amnesia Diseases 0.000 claims description 5
- 208000031091 Amnestic disease Diseases 0.000 claims description 5
- 230000006986 amnesia Effects 0.000 claims description 5
- 230000004770 neurodegeneration Effects 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 239000004480 active ingredient Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 125000003710 aryl alkyl group Chemical group 0.000 abstract 1
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 46
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
- 230000003078 antioxidant effect Effects 0.000 description 19
- ZFCQLDAGNBFMJQ-QUCCMNQESA-N apovincaminic acid Chemical class C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C=C(C(O)=O)N5C2=C1 ZFCQLDAGNBFMJQ-QUCCMNQESA-N 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 239000003963 antioxidant agent Substances 0.000 description 11
- 235000006708 antioxidants Nutrition 0.000 description 11
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 10
- 230000002253 anti-ischaemic effect Effects 0.000 description 10
- 229940093499 ethyl acetate Drugs 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- JGPMMRGNQUBGND-UHFFFAOYSA-N idebenone Chemical compound COC1=C(OC)C(=O)C(CCCCCCCCCCO)=C(C)C1=O JGPMMRGNQUBGND-UHFFFAOYSA-N 0.000 description 10
- 229960004135 idebenone Drugs 0.000 description 10
- 230000003496 anti-amnesic effect Effects 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 8
- 210000004556 brain Anatomy 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 238000007912 intraperitoneal administration Methods 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000002274 desiccant Substances 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 230000006378 damage Effects 0.000 description 6
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- 238000000338 in vitro Methods 0.000 description 6
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 208000027418 Wounds and injury Diseases 0.000 description 5
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 5
- 229960003529 diazepam Drugs 0.000 description 5
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- 239000012071 phase Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 4
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- DDNCQMVWWZOMLN-IRLDBZIGSA-N Vinpocetine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C=C(C(=O)OCC)N5C2=C1 DDNCQMVWWZOMLN-IRLDBZIGSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 208000004793 anterograde amnesia Diseases 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 210000001715 carotid artery Anatomy 0.000 description 4
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- SEBFKMXJBCUCAI-HKTJVKLFSA-N silibinin Chemical compound C1=C(O)C(OC)=CC([C@@H]2[C@H](OC3=CC=C(C=C3O2)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)CO)=C1 SEBFKMXJBCUCAI-HKTJVKLFSA-N 0.000 description 4
- 229960000744 vinpocetine Drugs 0.000 description 4
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 3
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 3
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- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229930003427 Vitamin E Natural products 0.000 description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
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- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
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- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 235000017700 silymarin Nutrition 0.000 description 3
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- 238000003756 stirring Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000011709 vitamin E Substances 0.000 description 3
- 235000019165 vitamin E Nutrition 0.000 description 3
- 229940046009 vitamin E Drugs 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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- FAARLWTXUUQFSN-UHFFFAOYSA-N methylellagic acid Natural products O1C(=O)C2=CC(O)=C(O)C3=C2C2=C1C(OC)=C(O)C=C2C(=O)O3 FAARLWTXUUQFSN-UHFFFAOYSA-N 0.000 description 1
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- 231100000252 nontoxic Toxicity 0.000 description 1
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
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- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
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- 229960002752 progabide Drugs 0.000 description 1
- IBALRBWGSVJPAP-HEHNFIMWSA-N progabide Chemical compound C=1C(F)=CC=C(O)C=1C(=N/CCCC(=O)N)/C1=CC=C(Cl)C=C1 IBALRBWGSVJPAP-HEHNFIMWSA-N 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 201000009570 retrograde amnesia Diseases 0.000 description 1
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- 229920006395 saturated elastomer Polymers 0.000 description 1
- CYGIJEJDYJOUAN-JSGXPVSSSA-N silydianin Chemical compound C1=C(O)C(OC)=CC([C@H]2[C@H]3C=C([C@@H]4[C@@](C3=O)(O)OC[C@@H]42)[C@@H]2[C@H](C(=O)C3=C(O)C=C(O)C=C3O2)O)=C1 CYGIJEJDYJOUAN-JSGXPVSSSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
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- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
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- 230000002889 sympathetic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 230000001515 vagal effect Effects 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D461/00—Heterocyclic compounds containing indolo [3,2,1-d,e] pyrido [3,2,1,j] [1,5]-naphthyridine ring systems, e.g. vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
-
- 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
- A61P25/28—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
- A61P3/00—Drugs for disorders of the metabolism
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Vascular Medicine (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9503736A HU214600B (hu) | 1995-12-22 | 1995-12-22 | Transz-apovinkaminsav-észter-származékok, az azokat tartalmazó gyógyszerkészítmények és eljárás ezek előállítására |
| PCT/HU1996/000075 WO1997023481A1 (en) | 1995-12-22 | 1996-12-13 | Trans apovincaminic acid ester derivatives as drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL124097A true IL124097A (en) | 2001-12-23 |
Family
ID=10987512
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12409796A IL124097A (en) | 1995-12-22 | 1996-12-13 | History of trans-avincaminic acid esters, their preparation, pharmaceutical preparations containing them and their use as medicines |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6093720A (cs) |
| EP (1) | EP0876367B1 (cs) |
| JP (1) | JP2000502676A (cs) |
| KR (1) | KR19990076606A (cs) |
| CN (1) | CN1072670C (cs) |
| AR (1) | AR005182A1 (cs) |
| AT (1) | ATE223914T1 (cs) |
| AU (1) | AU1166997A (cs) |
| CA (1) | CA2238635A1 (cs) |
| CZ (1) | CZ290383B6 (cs) |
| DE (1) | DE69623656T2 (cs) |
| DK (1) | DK0876367T3 (cs) |
| ES (1) | ES2181926T3 (cs) |
| HU (1) | HU214600B (cs) |
| IL (1) | IL124097A (cs) |
| PL (1) | PL186626B1 (cs) |
| PT (1) | PT876367E (cs) |
| RU (1) | RU2161157C2 (cs) |
| TW (1) | TW366348B (cs) |
| UA (1) | UA61062C2 (cs) |
| WO (1) | WO1997023481A1 (cs) |
| ZA (1) | ZA9610646B (cs) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006054536A1 (ja) * | 2004-11-16 | 2006-05-26 | Nippon Shinyaku Co., Ltd. | 尿路結石症治療剤 |
| JP2008017734A (ja) * | 2006-07-11 | 2008-01-31 | Memory Secret Inc | 精神的機能を改善するための栄養補助及び栄養摂取食品用の口経投与組成物 |
| CN102485723A (zh) * | 2010-12-02 | 2012-06-06 | 江苏斯威森生物医药工程研究中心有限公司 | 一锅法半合成长春西汀及其水溶性盐制备 |
| CN114920743B (zh) * | 2022-05-09 | 2023-08-04 | 南京中医药大学 | 一种吲哚生物碱及其制备方法与应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2531108A1 (de) * | 1975-07-11 | 1977-02-03 | Synthelabo | Vincaminderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel |
| HU186891B (en) * | 1981-06-12 | 1985-10-28 | Richter Gedeon Vegyeszet | Process for producing esters of apovincaminic acid |
| IT1142026B (it) * | 1981-07-21 | 1986-10-08 | Ausonia Farma Srl | Nuovo composto ad attivita' eumetabolica cerebrale |
| HU187733B (en) * | 1982-06-30 | 1986-02-28 | Richter Gedeon Vegyeszeti Gyar Rt,Hu | Process for preparing apovincaminic acid derivatives |
| JPS60248688A (ja) * | 1984-05-24 | 1985-12-09 | Sanwa Kagaku Kenkyusho:Kk | 新規のアポビンカミン酸エステルおよびその酸付加塩並びにその製造方法 |
-
1995
- 1995-12-22 HU HU9503736A patent/HU214600B/hu not_active IP Right Cessation
-
1996
- 1996-12-13 JP JP09523441A patent/JP2000502676A/ja not_active Withdrawn
- 1996-12-13 CN CN96199131A patent/CN1072670C/zh not_active Expired - Fee Related
- 1996-12-13 WO PCT/HU1996/000075 patent/WO1997023481A1/en not_active Ceased
- 1996-12-13 IL IL12409796A patent/IL124097A/en not_active IP Right Cessation
- 1996-12-13 CZ CZ19981962A patent/CZ290383B6/cs not_active IP Right Cessation
- 1996-12-13 DK DK96942534T patent/DK0876367T3/da active
- 1996-12-13 EP EP96942534A patent/EP0876367B1/en not_active Expired - Lifetime
- 1996-12-13 ES ES96942534T patent/ES2181926T3/es not_active Expired - Lifetime
- 1996-12-13 CA CA002238635A patent/CA2238635A1/en not_active Abandoned
- 1996-12-13 PT PT96942534T patent/PT876367E/pt unknown
- 1996-12-13 UA UA98052781A patent/UA61062C2/uk unknown
- 1996-12-13 AT AT96942534T patent/ATE223914T1/de not_active IP Right Cessation
- 1996-12-13 RU RU98113854/04A patent/RU2161157C2/ru not_active IP Right Cessation
- 1996-12-13 AU AU11669/97A patent/AU1166997A/en not_active Abandoned
- 1996-12-13 US US09/091,260 patent/US6093720A/en not_active Expired - Fee Related
- 1996-12-13 KR KR1019980704700A patent/KR19990076606A/ko not_active Abandoned
- 1996-12-13 DE DE69623656T patent/DE69623656T2/de not_active Expired - Fee Related
- 1996-12-13 PL PL96328170A patent/PL186626B1/pl not_active IP Right Cessation
- 1996-12-16 TW TW085115515A patent/TW366348B/zh active
- 1996-12-18 ZA ZA9610646A patent/ZA9610646B/xx unknown
- 1996-12-20 AR ARP960105829A patent/AR005182A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DE69623656T2 (de) | 2003-05-22 |
| JP2000502676A (ja) | 2000-03-07 |
| HU214600B (hu) | 1998-04-28 |
| WO1997023481A1 (en) | 1997-07-03 |
| CZ290383B6 (cs) | 2002-07-17 |
| EP0876367A1 (en) | 1998-11-11 |
| HUT76555A (en) | 1997-09-29 |
| AR005182A1 (es) | 1999-04-14 |
| HU9503736D0 (en) | 1996-02-28 |
| CN1205701A (zh) | 1999-01-20 |
| KR19990076606A (ko) | 1999-10-15 |
| US6093720A (en) | 2000-07-25 |
| CZ196298A3 (cs) | 1998-10-14 |
| ATE223914T1 (de) | 2002-09-15 |
| PL186626B1 (pl) | 2004-02-27 |
| DK0876367T3 (da) | 2002-12-30 |
| PT876367E (pt) | 2003-01-31 |
| CN1072670C (zh) | 2001-10-10 |
| DE69623656D1 (en) | 2002-10-17 |
| CA2238635A1 (en) | 1997-07-03 |
| ES2181926T3 (es) | 2003-03-01 |
| AU1166997A (en) | 1997-07-17 |
| PL328170A1 (en) | 1999-01-18 |
| EP0876367B1 (en) | 2002-09-11 |
| ZA9610646B (en) | 1997-06-24 |
| TW366348B (en) | 1999-08-11 |
| RU2161157C2 (ru) | 2000-12-27 |
| UA61062C2 (en) | 2003-11-17 |
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| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |