CA1085827A - Derivatives of vincamine and apovincamine and related preparation process - Google Patents
Derivatives of vincamine and apovincamine and related preparation processInfo
- Publication number
- CA1085827A CA1085827A CA279,705A CA279705A CA1085827A CA 1085827 A CA1085827 A CA 1085827A CA 279705 A CA279705 A CA 279705A CA 1085827 A CA1085827 A CA 1085827A
- Authority
- CA
- Canada
- Prior art keywords
- apovincamine
- vincamine
- acid
- reacted
- glucose
- 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
Links
- RXPRRQLKFXBCSJ-GIVPXCGWSA-N vincamine Chemical class C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-GIVPXCGWSA-N 0.000 title claims abstract description 317
- 229950006936 apovincamine Drugs 0.000 title claims abstract description 146
- OZDNDGXASTWERN-UHFFFAOYSA-N apovincamine Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)C=C(C(=O)OC)N5C2=C1 OZDNDGXASTWERN-UHFFFAOYSA-N 0.000 title claims abstract description 146
- OZDNDGXASTWERN-CTNGQTDRSA-N Apovincamine Chemical compound C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C=C(C(=O)OC)N5C2=C1 OZDNDGXASTWERN-CTNGQTDRSA-N 0.000 title claims abstract description 143
- 238000002360 preparation method Methods 0.000 title abstract description 6
- RXPRRQLKFXBCSJ-UHFFFAOYSA-N dl-Vincamin Natural products C1=CC=C2C(CCN3CCC4)=C5C3C4(CC)CC(O)(C(=O)OC)N5C2=C1 RXPRRQLKFXBCSJ-UHFFFAOYSA-N 0.000 claims abstract description 160
- 229960002726 vincamine Drugs 0.000 claims abstract description 160
- 238000000034 method Methods 0.000 claims abstract description 95
- 150000001875 compounds Chemical class 0.000 claims abstract description 21
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 9
- 230000000694 effects Effects 0.000 claims abstract description 6
- 230000008569 process Effects 0.000 claims description 70
- 150000003839 salts Chemical class 0.000 claims description 62
- 239000000126 substance Substances 0.000 claims description 45
- 239000002253 acid Substances 0.000 claims description 23
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 17
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 claims description 15
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 claims description 15
- 239000001814 pectin Substances 0.000 claims description 13
- 229920001277 pectin Polymers 0.000 claims description 13
- 238000003756 stirring Methods 0.000 claims description 13
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 claims description 11
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 11
- 235000010987 pectin Nutrition 0.000 claims description 11
- 239000000725 suspension Substances 0.000 claims description 11
- 230000007935 neutral effect Effects 0.000 claims description 10
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 9
- 235000010443 alginic acid Nutrition 0.000 claims description 9
- 229920000615 alginic acid Polymers 0.000 claims description 9
- 229960004502 levodopa Drugs 0.000 claims description 9
- WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 claims description 8
- 229960004337 hydroquinone Drugs 0.000 claims description 8
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 8
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 7
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 7
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 claims description 7
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 7
- SODPIMGUZLOIPE-UHFFFAOYSA-N (4-chlorophenoxy)acetic acid Chemical compound OC(=O)COC1=CC=C(Cl)C=C1 SODPIMGUZLOIPE-UHFFFAOYSA-N 0.000 claims description 6
- UYEMGAFJOZZIFP-UHFFFAOYSA-N 3,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC(O)=C1 UYEMGAFJOZZIFP-UHFFFAOYSA-N 0.000 claims description 6
- UZTFMUBKZQVKLK-UHFFFAOYSA-N 4-acetamidobutanoic acid Chemical compound CC(=O)NCCCC(O)=O UZTFMUBKZQVKLK-UHFFFAOYSA-N 0.000 claims description 6
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 6
- 235000001968 nicotinic acid Nutrition 0.000 claims description 6
- 239000011664 nicotinic acid Substances 0.000 claims description 6
- UIAFKZKHHVMJGS-UHFFFAOYSA-N 2,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1O UIAFKZKHHVMJGS-UHFFFAOYSA-N 0.000 claims description 5
- HCYFGRCYSCXKNQ-UHFFFAOYSA-M 2-(1,3-dimethyl-2,6-dioxopurin-7-yl)acetate Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC([O-])=O)C=N2 HCYFGRCYSCXKNQ-UHFFFAOYSA-M 0.000 claims description 5
- 239000000783 alginic acid Substances 0.000 claims description 5
- 229960001126 alginic acid Drugs 0.000 claims description 5
- 150000004781 alginic acids Chemical class 0.000 claims description 5
- VQLXCAHGUGIEEL-FAOVPRGRSA-L disodium;[(2r,3r,4s,5r)-2,3,4,5-tetrahydroxy-6-oxohexyl] phosphate Chemical compound [Na+].[Na+].[O-]P(=O)([O-])OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O VQLXCAHGUGIEEL-FAOVPRGRSA-L 0.000 claims description 5
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 claims description 5
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 claims description 5
- 229950010765 pivalate Drugs 0.000 claims description 5
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 4
- 229920002253 Tannate Polymers 0.000 claims description 4
- 229940068372 acetyl salicylate Drugs 0.000 claims description 4
- 229940072056 alginate Drugs 0.000 claims description 4
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 claims description 4
- 229960001214 clofibrate Drugs 0.000 claims description 4
- GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 claims description 4
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 4
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 claims description 3
- HCYFGRCYSCXKNQ-UHFFFAOYSA-N 2-(1,3-dimethyl-2,6-dioxo-7-purinyl)acetic acid Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC(O)=O)C=N2 HCYFGRCYSCXKNQ-UHFFFAOYSA-N 0.000 claims description 3
- UIAFKZKHHVMJGS-UHFFFAOYSA-M 2-carboxy-5-hydroxyphenolate Chemical compound OC1=CC=C(C([O-])=O)C(O)=C1 UIAFKZKHHVMJGS-UHFFFAOYSA-M 0.000 claims description 3
- 239000001263 FEMA 3042 Substances 0.000 claims description 3
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 claims description 3
- TXCGAZHTZHNUAI-UHFFFAOYSA-N clofibric acid Chemical compound OC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 TXCGAZHTZHNUAI-UHFFFAOYSA-N 0.000 claims description 3
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 3
- 229960002510 mandelic acid Drugs 0.000 claims description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 3
- 229960001860 salicylate Drugs 0.000 claims description 3
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 3
- 229960004889 salicylic acid Drugs 0.000 claims description 3
- 229940033123 tannic acid Drugs 0.000 claims description 3
- 235000015523 tannic acid Nutrition 0.000 claims description 3
- 229920002258 tannic acid Polymers 0.000 claims description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
- 239000003315 2-(4-chlorophenoxy)-2-methylpropanoic acid Substances 0.000 claims description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 229950008441 clofibric acid Drugs 0.000 claims description 2
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims description 2
- 229960003512 nicotinic acid Drugs 0.000 claims description 2
- HXXFSFRBOHSIMQ-VFUOTHLCSA-N alpha-D-glucose 1-phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(O)=O)[C@H](O)[C@@H](O)[C@@H]1O HXXFSFRBOHSIMQ-VFUOTHLCSA-N 0.000 claims 10
- 229950010772 glucose-1-phosphate Drugs 0.000 claims 10
- 229940045189 glucose-6-phosphate Drugs 0.000 claims 10
- INXMOHFFQYLBED-CXWKFSMRSA-L disodium;[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate;tetrahydrate Chemical compound O.O.O.O.[Na+].[Na+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@@H]1O INXMOHFFQYLBED-CXWKFSMRSA-L 0.000 claims 6
- AKEUNCKRJATALU-UHFFFAOYSA-N 2,6-dihydroxybenzoic acid Chemical compound OC(=O)C1=C(O)C=CC=C1O AKEUNCKRJATALU-UHFFFAOYSA-N 0.000 claims 2
- 229940114055 beta-resorcylic acid Drugs 0.000 claims 2
- 229960000292 pectin Drugs 0.000 claims 2
- AKEUNCKRJATALU-UHFFFAOYSA-M 2,6-dihydroxybenzoate Chemical compound OC1=CC=CC(O)=C1C([O-])=O AKEUNCKRJATALU-UHFFFAOYSA-M 0.000 claims 1
- MIOPJNTWMNEORI-OMNKOJBGSA-N [(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methanesulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-OMNKOJBGSA-N 0.000 claims 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 claims 1
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 150000007524 organic acids Chemical class 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 85
- 235000019441 ethanol Nutrition 0.000 description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- 238000002844 melting Methods 0.000 description 43
- 230000008018 melting Effects 0.000 description 43
- 239000000047 product Substances 0.000 description 36
- 239000000203 mixture Substances 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- HXXFSFRBOHSIMQ-UHFFFAOYSA-N [3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] dihydrogen phosphate Chemical compound OCC1OC(OP(O)(O)=O)C(O)C(O)C1O HXXFSFRBOHSIMQ-UHFFFAOYSA-N 0.000 description 15
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 8
- 230000002490 cerebral effect Effects 0.000 description 7
- 238000001556 precipitation Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 229940071221 dihydroxybenzoate Drugs 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000009835 boiling Methods 0.000 description 4
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 4
- 229960004132 diethyl ether Drugs 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- -1 glucose-l-phosphate tetrahydrate Chemical class 0.000 description 4
- 239000012456 homogeneous solution Substances 0.000 description 4
- 230000002035 prolonged effect Effects 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- YGKAKNJJNTVSKB-YAFGAGFVSA-N vincamine hydrochloride Chemical compound Cl.C1=CC=C2C(CCN3CCC4)=C5[C@@H]3[C@]4(CC)C[C@](O)(C(=O)OC)N5C2=C1 YGKAKNJJNTVSKB-YAFGAGFVSA-N 0.000 description 3
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000008279 sol Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 230000000304 vasodilatating effect Effects 0.000 description 2
- NDVRKEKNSBMTAX-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O NDVRKEKNSBMTAX-BTVCFUMJSA-N 0.000 description 1
- GLDQAMYCGOIJDV-UHFFFAOYSA-N 2,3-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC(O)=C1O GLDQAMYCGOIJDV-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- 150000005166 2-hydroxybenzoic acids Chemical class 0.000 description 1
- YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
- 150000005178 3,5-dihydroxybenzoic acids Chemical class 0.000 description 1
- JXQCUCDXLSGQNZ-UHFFFAOYSA-N 3-tert-butyl-2-hydroxy-6-methylbenzoic acid Chemical compound CC1=CC=C(C(C)(C)C)C(O)=C1C(O)=O JXQCUCDXLSGQNZ-UHFFFAOYSA-N 0.000 description 1
- 150000005168 4-hydroxybenzoic acids Chemical class 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- RJUFJBKOKNCXHH-UHFFFAOYSA-N Methyl propionate Chemical compound CCC(=O)OC RJUFJBKOKNCXHH-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- 229940022682 acetone Drugs 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000003191 femoral vein Anatomy 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 201000005851 intracranial arteriosclerosis Diseases 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940017219 methyl propionate Drugs 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-N methyl sulfate Chemical compound COS(O)(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000010415 tropism Effects 0.000 description 1
- 210000002385 vertebral artery Anatomy 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
- 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH7039/76 | 1976-06-03 | ||
| CH703976A CH625240A5 (en) | 1976-06-03 | 1976-06-03 | Process for preparing novel derivatives of vincamine and apovincamine |
| CH704076A CH625241A5 (en) | 1976-06-03 | 1976-06-03 | Process for preparing novel salts of vincamine and apovincamine |
| CH7040/76 | 1976-06-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1085827A true CA1085827A (en) | 1980-09-16 |
Family
ID=25700616
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA279,705A Expired CA1085827A (en) | 1976-06-03 | 1977-06-02 | Derivatives of vincamine and apovincamine and related preparation process |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4122179A (en, 2012) |
| JP (1) | JPS52151715A (en, 2012) |
| AU (1) | AU514744B2 (en, 2012) |
| CA (1) | CA1085827A (en, 2012) |
| DE (1) | DE2725246A1 (en, 2012) |
| ES (1) | ES459423A1 (en, 2012) |
| FR (1) | FR2353551A1 (en, 2012) |
| GB (1) | GB1549501A (en, 2012) |
| IE (1) | IE790258L (en, 2012) |
| IT (1) | IT1074400B (en, 2012) |
| NL (1) | NL7706046A (en, 2012) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1117939A (en) * | 1978-02-15 | 1982-02-09 | Enrico C. Mora | Derivatives of eburnamomine and related method of manufacturing |
| US4362730A (en) * | 1980-08-25 | 1982-12-07 | Heinrich Mack Nachf. Chem-Pharm. Fabrik | Vincamine saccharinate and a pharmaceutical composition containing it dissolved therein |
| DE3113132A1 (de) * | 1981-04-01 | 1982-10-21 | Heinrich Mack Nachf., 7918 Illertissen | Vincamin-cyclamat, verfahren zu seiner herstellung und dieses enthaltende arzneimittel |
| EP0154756B2 (fr) * | 1984-02-29 | 1996-10-23 | Covex (S.A.) | Citrate de vinpocetine et son procédé de préparation |
| US5506210A (en) * | 1988-08-19 | 1996-04-09 | The Australian National University | Phosphosugar-based anti-inflammatory and/or immunosuppressive drugs |
| WO1990001938A1 (en) * | 1988-08-19 | 1990-03-08 | The Australian National University | Phosphosugar-based anti-inflammatory and/or immunosuppressive drugs |
| DE4011285A1 (de) * | 1990-04-06 | 1991-10-10 | Steigerwald Arzneimittelwerk | Arzneimittel zur behandlung von hyperlipidaemie und/oder atherosklerose |
| JP4485169B2 (ja) * | 2003-05-16 | 2010-06-16 | 花王株式会社 | 腸管ミネラル吸収能改善剤 |
| US20050003047A1 (en) * | 2003-05-16 | 2005-01-06 | Kao Corporation | Intestinal mineral absorption capacity improver |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3450814A (en) * | 1964-07-15 | 1969-06-17 | Chemway Corp | Ophthalmic compositions containing alginic acid salts of pilocarpine,atropine and physostigmine |
| FR2155889A1 (en) * | 1971-10-13 | 1973-05-25 | Buzas Andre | Vincamine theophyllinepropanesulphonate - with cerebral vasodilatory activity |
| BE790837A (fr) * | 1971-11-03 | 1973-02-15 | Richter Gedeon Vegeon Vegyesze | Nouveaux esters alcaloides utiles comme vasodilatateurs cerebraux et leur procede de preparation |
| FR2179538B1 (en, 2012) * | 1972-04-11 | 1975-04-25 | Merrell Toraude & Co | |
| FR2191891B1 (en, 2012) * | 1972-07-13 | 1975-08-08 | Roussel Uclaf | |
| FR2201898A1 (en) * | 1973-05-30 | 1974-05-03 | Sogeras | Vincamine arabogalactan sulphate - with prolonged activity for treating cerebrovascular disorders |
| FR2255885B1 (en, 2012) * | 1973-12-28 | 1977-09-09 | Centre Etd Ind Pharma | |
| CH585226A5 (en) * | 1974-03-08 | 1977-02-28 | Vifor Sa | Slightly soluble vincamine pamoates - with long duration of action as cerebral vasodilators |
| FR2274283A1 (fr) * | 1974-06-12 | 1976-01-09 | Castaigne Sa | Nouveau sel de vincamine |
| FR2283669A1 (fr) * | 1974-09-06 | 1976-04-02 | Elmu Sa | 2-cetoglutarate de vincamine et son procede de preparation |
| ES430059A1 (es) * | 1974-09-14 | 1976-10-16 | Roger Lab | Procedimiento para la obtencion de un nuevo derivado del a-cido nicotinico. |
-
1977
- 1977-05-27 US US05/801,209 patent/US4122179A/en not_active Expired - Lifetime
- 1977-05-27 GB GB22545/77A patent/GB1549501A/en not_active Expired
- 1977-06-02 ES ES459423A patent/ES459423A1/es not_active Expired
- 1977-06-02 NL NL7706046A patent/NL7706046A/xx not_active Application Discontinuation
- 1977-06-02 AU AU25797/77A patent/AU514744B2/en not_active Expired
- 1977-06-02 CA CA279,705A patent/CA1085827A/en not_active Expired
- 1977-06-03 JP JP6492477A patent/JPS52151715A/ja active Pending
- 1977-06-03 IT IT24384/77A patent/IT1074400B/it active
- 1977-06-03 FR FR7717086A patent/FR2353551A1/fr active Granted
- 1977-06-03 DE DE19772725246 patent/DE2725246A1/de active Granted
-
1979
- 1979-02-12 IE IE790258A patent/IE790258L/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2579777A (en) | 1978-12-07 |
| GB1549501A (en) | 1979-08-08 |
| FR2353551B1 (en, 2012) | 1980-12-12 |
| NL7706046A (nl) | 1977-12-06 |
| ES459423A1 (es) | 1978-11-01 |
| JPS52151715A (en) | 1977-12-16 |
| IT1074400B (it) | 1985-04-20 |
| FR2353551A1 (fr) | 1977-12-30 |
| US4122179A (en) | 1978-10-24 |
| AU514744B2 (en) | 1981-02-26 |
| IE790258L (en) | 1979-08-15 |
| DE2725246A1 (de) | 1977-12-22 |
| DE2725246C2 (en, 2012) | 1989-09-07 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |