JP5265691B2 - リグストラジン芳香族酸エーテル類化合物、生成方法と薬物化合物及び応用 - Google Patents
リグストラジン芳香族酸エーテル類化合物、生成方法と薬物化合物及び応用 Download PDFInfo
- Publication number
- JP5265691B2 JP5265691B2 JP2010530261A JP2010530261A JP5265691B2 JP 5265691 B2 JP5265691 B2 JP 5265691B2 JP 2010530261 A JP2010530261 A JP 2010530261A JP 2010530261 A JP2010530261 A JP 2010530261A JP 5265691 B2 JP5265691 B2 JP 5265691B2
- Authority
- JP
- Japan
- Prior art keywords
- acid
- compound
- trimethylpyrazine
- salt
- ligustrazine
- 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.)
- Active
Links
- FINHMKGKINIASC-UHFFFAOYSA-N tetramethyl-pyrazine Natural products CC1=NC(C)=C(C)N=C1C FINHMKGKINIASC-UHFFFAOYSA-N 0.000 title claims abstract description 54
- -1 Ligustrazine aromatic acid ether compound Chemical class 0.000 title claims abstract description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 title claims description 50
- 239000003814 drug Substances 0.000 title claims description 28
- 150000001875 compounds Chemical class 0.000 title claims description 27
- 229940079593 drug Drugs 0.000 title claims description 24
- 238000004519 manufacturing process Methods 0.000 title claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- 238000006243 chemical reaction Methods 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- 239000000047 product Substances 0.000 claims description 22
- 239000007787 solid Substances 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- HOPVUIZLMIEGMJ-UHFFFAOYSA-N 2-(bromomethyl)-3,5,6-trimethylpyrazine Chemical compound CC1=NC(C)=C(CBr)N=C1C HOPVUIZLMIEGMJ-UHFFFAOYSA-N 0.000 claims description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 18
- 239000003960 organic solvent Substances 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 15
- 239000003513 alkali Substances 0.000 claims description 13
- 239000000706 filtrate Substances 0.000 claims description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 10
- 238000000926 separation method Methods 0.000 claims description 9
- SWGJCIMEBVHMTA-UHFFFAOYSA-K trisodium;6-oxido-4-sulfo-5-[(4-sulfonatonaphthalen-1-yl)diazenyl]naphthalene-2-sulfonate Chemical compound [Na+].[Na+].[Na+].C1=CC=C2C(N=NC3=C4C(=CC(=CC4=CC=C3O)S([O-])(=O)=O)S([O-])(=O)=O)=CC=C(S([O-])(=O)=O)C2=C1 SWGJCIMEBVHMTA-UHFFFAOYSA-K 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 208000001435 Thromboembolism Diseases 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 238000000746 purification Methods 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims description 5
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- GKIIUOKTDCNMFK-SOFGYWHQSA-N (e)-3-[3-methoxy-4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]phenyl]prop-2-enoic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1OCC1=NC(C)=C(C)N=C1C GKIIUOKTDCNMFK-SOFGYWHQSA-N 0.000 claims description 3
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 3
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 3
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 3
- 238000006460 hydrolysis reaction Methods 0.000 claims description 3
- IAEGWXHKWJGQAZ-UHFFFAOYSA-N trimethylpyrazine Chemical compound CC1=CN=C(C)C(C)=N1 IAEGWXHKWJGQAZ-UHFFFAOYSA-N 0.000 claims description 3
- TYZVLOKXCAMNQF-UHFFFAOYSA-N 4-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoic acid Chemical compound N1=C(C)C(C)=NC(C)=C1COC1=CC=C(C(O)=O)C=C1 TYZVLOKXCAMNQF-UHFFFAOYSA-N 0.000 claims description 2
- POSNCTVMUZDYGJ-UHFFFAOYSA-N 4-methoxy-3-[(3,5,6-trimethylpyrazin-2-yl)methoxy]benzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1OCC1=NC(C)=C(C)N=C1C POSNCTVMUZDYGJ-UHFFFAOYSA-N 0.000 claims description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- PCSMJKASWLYICJ-UHFFFAOYSA-N Succinic aldehyde Chemical compound O=CCCC=O PCSMJKASWLYICJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical group 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- 230000003197 catalytic effect Effects 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical group [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 2
- 239000001294 propane Substances 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims description 2
- 159000000000 sodium salts Chemical class 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 238000005292 vacuum distillation Methods 0.000 claims description 2
- 150000002148 esters Chemical group 0.000 claims 3
- 238000010992 reflux Methods 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 2
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 238000002360 preparation method Methods 0.000 abstract 1
- 125000005504 styryl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
- KFHRMMHGGBCRIV-UHFFFAOYSA-N 2-azaniumyl-4-methoxybutanoate Chemical compound COCCC(N)C(O)=O KFHRMMHGGBCRIV-UHFFFAOYSA-N 0.000 description 34
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 29
- 230000015572 biosynthetic process Effects 0.000 description 28
- 238000005481 NMR spectroscopy Methods 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 22
- 239000003795 chemical substances by application Substances 0.000 description 16
- 238000011084 recovery Methods 0.000 description 15
- 239000003208 petroleum Substances 0.000 description 14
- 239000002994 raw material Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 208000007536 Thrombosis Diseases 0.000 description 11
- 239000003146 anticoagulant agent Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- 239000005711 Benzoic acid Substances 0.000 description 9
- 230000002776 aggregation Effects 0.000 description 9
- 238000004220 aggregation Methods 0.000 description 9
- 235000010233 benzoic acid Nutrition 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- SHZKQBHERIJWAO-AATRIKPKSA-N ozagrel Chemical compound C1=CC(/C=C/C(=O)O)=CC=C1CN1C=NC=C1 SHZKQBHERIJWAO-AATRIKPKSA-N 0.000 description 8
- 229950003837 ozagrel Drugs 0.000 description 8
- 230000000702 anti-platelet effect Effects 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 238000007689 inspection Methods 0.000 description 7
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 5
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 5
- 230000009471 action Effects 0.000 description 5
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 5
- 210000004623 platelet-rich plasma Anatomy 0.000 description 5
- 229910052710 silicon Inorganic materials 0.000 description 5
- 239000010703 silicon Substances 0.000 description 5
- KSEBMYQBYZTDHS-HWKANZROSA-M (E)-Ferulic acid Natural products COC1=CC(\C=C\C([O-])=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-M 0.000 description 4
- 229940127219 anticoagulant drug Drugs 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 4
- KSEBMYQBYZTDHS-HWKANZROSA-N ferulic acid Chemical compound COC1=CC(\C=C\C(O)=O)=CC=C1O KSEBMYQBYZTDHS-HWKANZROSA-N 0.000 description 4
- 229940114124 ferulic acid Drugs 0.000 description 4
- 235000001785 ferulic acid Nutrition 0.000 description 4
- KSEBMYQBYZTDHS-UHFFFAOYSA-N ferulic acid Natural products COC1=CC(C=CC(O)=O)=CC=C1O KSEBMYQBYZTDHS-UHFFFAOYSA-N 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QURCVMIEKCOAJU-UHFFFAOYSA-N trans-isoferulic acid Natural products COC1=CC=C(C=CC(O)=O)C=C1O QURCVMIEKCOAJU-UHFFFAOYSA-N 0.000 description 4
- 240000008067 Cucumis sativus Species 0.000 description 3
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 3
- 229940127218 antiplatelet drug Drugs 0.000 description 3
- 230000000740 bleeding effect Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 206010008118 cerebral infarction Diseases 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- RQKFOGXUTRDQPB-UHFFFAOYSA-N hydron;2,3,5,6-tetramethylpyrazine;chloride Chemical compound Cl.CC1=NC(C)=C(C)N=C1C RQKFOGXUTRDQPB-UHFFFAOYSA-N 0.000 description 3
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 3
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 2
- IWPZKOJSYQZABD-UHFFFAOYSA-N 3,5-dimethoxybenzoic acid Chemical compound COC1=CC(OC)=CC(C(O)=O)=C1 IWPZKOJSYQZABD-UHFFFAOYSA-N 0.000 description 2
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 2
- 108010003541 Platelet Activating Factor Proteins 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 208000029078 coronary artery disease Diseases 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003527 fibrinolytic agent Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- BVWTXUYLKBHMOX-UHFFFAOYSA-N methyl vanillate Chemical compound COC(=O)C1=CC=C(O)C(OC)=C1 BVWTXUYLKBHMOX-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 125000003011 styrenyl group Chemical group [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- PECUPOXPPBBFLU-UHFFFAOYSA-N 1-ethenyl-3-methoxybenzene Chemical compound COC1=CC=CC(C=C)=C1 PECUPOXPPBBFLU-UHFFFAOYSA-N 0.000 description 1
- DUAYDERMVQWIJD-UHFFFAOYSA-N 2-n,2-n,6-trimethyl-1,3,5-triazine-2,4-diamine Chemical compound CN(C)C1=NC(C)=NC(N)=N1 DUAYDERMVQWIJD-UHFFFAOYSA-N 0.000 description 1
- QQOMQLYQAXGHSU-UHFFFAOYSA-N 236TMPh Natural products CC1=CC=C(C)C(O)=C1C QQOMQLYQAXGHSU-UHFFFAOYSA-N 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 240000007087 Apium graveolens Species 0.000 description 1
- 235000015849 Apium graveolens Dulce Group Nutrition 0.000 description 1
- 235000010591 Appio Nutrition 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 201000006474 Brain Ischemia Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 206010059109 Cerebral vasoconstriction Diseases 0.000 description 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- KBEBGUQPQBELIU-CMDGGOBGSA-N Ethyl cinnamate Chemical compound CCOC(=O)\C=C\C1=CC=CC=C1 KBEBGUQPQBELIU-CMDGGOBGSA-N 0.000 description 1
- 108010074860 Factor Xa Proteins 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 1
- 101710149643 Integrin alpha-IIb Proteins 0.000 description 1
- 241000112528 Ligusticum striatum Species 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 206010050661 Platelet aggregation inhibition Diseases 0.000 description 1
- 206010036790 Productive cough Diseases 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- IGWHDMPTQKSDTL-JXOAFFINSA-N TMP Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(O)=O)O1 IGWHDMPTQKSDTL-JXOAFFINSA-N 0.000 description 1
- 108010069102 Thromboxane-A synthase Proteins 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 208000007814 Unstable Angina Diseases 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 229960000446 abciximab Drugs 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 102000011759 adducin Human genes 0.000 description 1
- 108010076723 adducin Proteins 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- KXNPVXPOPUZYGB-XYVMCAHJSA-N argatroban Chemical compound OC(=O)[C@H]1C[C@H](C)CCN1C(=O)[C@H](CCCN=C(N)N)NS(=O)(=O)C1=CC=CC2=C1NC[C@H](C)C2 KXNPVXPOPUZYGB-XYVMCAHJSA-N 0.000 description 1
- 229960003856 argatroban Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- KYZHGEFMXZOSJN-UHFFFAOYSA-N benzoic acid isobutyl ester Natural products CC(C)COC(=O)C1=CC=CC=C1 KYZHGEFMXZOSJN-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
- 108010055460 bivalirudin Proteins 0.000 description 1
- 229960001500 bivalirudin Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- KBEBGUQPQBELIU-UHFFFAOYSA-N cinnamic acid ethyl ester Natural products CCOC(=O)C=CC1=CC=CC=C1 KBEBGUQPQBELIU-UHFFFAOYSA-N 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 108010055222 clotting enzyme Proteins 0.000 description 1
- 208000002528 coronary thrombosis Diseases 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- ATJVZXXHKSYELS-FNORWQNLSA-N ethyl (e)-3-(4-hydroxy-3-methoxyphenyl)prop-2-enoate Chemical compound CCOC(=O)\C=C\C1=CC=C(O)C(OC)=C1 ATJVZXXHKSYELS-FNORWQNLSA-N 0.000 description 1
- WKUVKFZZCHINKG-UHFFFAOYSA-N ethyl 4-hydroxy-3,5-dimethoxybenzoate Chemical compound CCOC(=O)C1=CC(OC)=C(O)C(OC)=C1 WKUVKFZZCHINKG-UHFFFAOYSA-N 0.000 description 1
- 229940027504 ethyl ferulate Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- ATJVZXXHKSYELS-UHFFFAOYSA-N ferulic acid ethyl ester Natural products CCOC(=O)C=CC1=CC=C(O)C(OC)=C1 ATJVZXXHKSYELS-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960001008 heparin sodium Drugs 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- WQPDUTSPKFMPDP-OUMQNGNKSA-N hirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(OS(O)(=O)=O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@@H]2CSSC[C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N2)=O)CSSC1)C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)CSSC1)C(C)C)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 WQPDUTSPKFMPDP-OUMQNGNKSA-N 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 208000001286 intracranial vasospasm Diseases 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000003055 low molecular weight heparin Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229940127215 low-molecular weight heparin Drugs 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 108010075698 monteplase Proteins 0.000 description 1
- 229950005805 monteplase Drugs 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102220047090 rs6152 Human genes 0.000 description 1
- FFYNAVGJSYHHFO-UHFFFAOYSA-N sarpogrelate Chemical compound COC1=CC=CC(CCC=2C(=CC=CC=2)OCC(CN(C)C)OC(=O)CCC(O)=O)=C1 FFYNAVGJSYHHFO-UHFFFAOYSA-N 0.000 description 1
- 229950005789 sarpogrelate Drugs 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 210000003802 sputum Anatomy 0.000 description 1
- 208000024794 sputum Diseases 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 150000003440 styrenes Chemical group 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 description 1
- COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 description 1
- 229960003425 tirofiban Drugs 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229940126680 traditional chinese medicines Drugs 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000036448 vitalisation Effects 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101634771A CN101143851B (zh) | 2007-10-26 | 2007-10-26 | 川芎嗪芳酸醚类衍生物、制备方法和药物组合物与应用 |
| CN200710163477.1 | 2007-10-26 | ||
| PCT/CN2008/072840 WO2009056070A1 (en) | 2007-10-26 | 2008-10-27 | Ligustrazine aromatic acid ether derivative, its preparation method, pharmaceutical composition, and application |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011500736A JP2011500736A (ja) | 2011-01-06 |
| JP2011500736A5 JP2011500736A5 (https=) | 2013-05-02 |
| JP5265691B2 true JP5265691B2 (ja) | 2013-08-14 |
Family
ID=39206606
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2010530261A Active JP5265691B2 (ja) | 2007-10-26 | 2008-10-27 | リグストラジン芳香族酸エーテル類化合物、生成方法と薬物化合物及び応用 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8350033B2 (https=) |
| EP (1) | EP2213666B1 (https=) |
| JP (1) | JP5265691B2 (https=) |
| CN (1) | CN101143851B (https=) |
| AT (1) | ATE545634T1 (https=) |
| ES (1) | ES2382979T3 (https=) |
| WO (1) | WO2009056070A1 (https=) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101143851B (zh) * | 2007-10-26 | 2010-07-21 | 李家明 | 川芎嗪芳酸醚类衍生物、制备方法和药物组合物与应用 |
| CN101812025B (zh) * | 2010-04-15 | 2011-12-07 | 李家明 | 吡嗪芳酸醚类化合物、制备方法和医药应用 |
| CN101851209B (zh) * | 2010-06-21 | 2012-09-19 | 合肥医工医药有限公司 | 咪唑乙基香草酸醚、其制备方法及其医药用途 |
| CN102675401B (zh) * | 2011-03-09 | 2014-08-13 | 雷海民 | 抗肿瘤药物lqc-y的制备及其应用 |
| CN104151388B (zh) * | 2011-03-09 | 2016-08-31 | 思路迪（北京）医药科技有限公司 | 抗肿瘤药物lqc-y的制备及其应用 |
| CN102675228B (zh) | 2011-03-16 | 2014-08-13 | 雷海民 | 一种治疗缺血性脑损伤中风及其后遗症的药物与制备方法 |
| CN103467383B (zh) * | 2013-09-13 | 2015-07-15 | 上海海虹实业(集团)巢湖今辰药业有限公司 | 一种丹皮酚与奥扎格雷偶联物及其药物组合物、医药用途 |
| CN104513207B (zh) * | 2013-10-08 | 2017-06-20 | 昆药集团股份有限公司 | 一种苄醇醚类化合物及其制备方法、制剂与应用 |
| CN104557740B (zh) * | 2013-10-17 | 2018-01-02 | 雷海民 | 具有神经保护活性的川芎嗪取代苯甲酸类衍生物(lqc‑a)及其应用 |
| CN103864768B (zh) * | 2014-03-04 | 2016-04-06 | 广西师范大学 | 川芎嗪茋类衍生物及其制备方法与应用 |
| CN105801496B (zh) * | 2014-12-31 | 2018-03-13 | 广州喜鹊医药有限公司 | 三氟乙酰肼类化合物及其制备方法和在制药中的应用 |
| CN105017165B (zh) * | 2015-07-07 | 2018-04-03 | 广州喜鹊医药有限公司 | 一种新的吡嗪衍生物及其制备方法和医药应用 |
| CN108456179B (zh) * | 2017-02-20 | 2021-09-28 | 雷鹏程 | 具有神经保护作用的化合物tva-x及其制备方法和应用 |
| CN107556251B (zh) * | 2017-08-23 | 2018-06-22 | 广东昊邦医药健康有限责任公司 | 一种磷酸川芎嗪衍生化合物及其药物组合物 |
| CN112028875B (zh) * | 2019-06-04 | 2023-08-15 | 南昌弘益科技有限公司 | 一类pgi2蛋白激动剂、txa2蛋白抑制剂的酸酐类化合物 |
| CN110749679B (zh) * | 2019-11-08 | 2022-11-01 | 华熙生物科技股份有限公司 | 一种三甲基吡嗪残留的检测方法 |
| CN111825664B (zh) * | 2020-08-01 | 2023-01-17 | 泰州学院 | 一种川芎嗪衍生物、制备方法和医药用途 |
| CN114805224B (zh) * | 2022-04-01 | 2024-03-22 | 山东大学 | 一种川芎嗪查尔酮衍生物及其制备方法与应用 |
| CN115201372B (zh) * | 2022-07-14 | 2023-11-10 | 四川新绿色药业科技发展有限公司 | 一种同时检测川芎和水蛭的薄层色谱方法 |
| CN116063237B (zh) * | 2023-02-20 | 2025-11-21 | 武汉科技大学 | 一类no供体型川芎嗪衍生物、制备方法、组合物及用途 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1184209C (zh) * | 2002-12-20 | 2005-01-12 | 山东大学 | 川芎醇酯类衍生物及其制备方法和含有川芎醇酯类衍生物的药物组合物与应用 |
| CN101012201B (zh) * | 2007-02-05 | 2010-07-28 | 中国药科大学 | 川芎嗪衍生物、其制备方法及其医药用途 |
| CN101143851B (zh) * | 2007-10-26 | 2010-07-21 | 李家明 | 川芎嗪芳酸醚类衍生物、制备方法和药物组合物与应用 |
-
2007
- 2007-10-26 CN CN2007101634771A patent/CN101143851B/zh active Active
-
2008
- 2008-10-27 ES ES08843800T patent/ES2382979T3/es active Active
- 2008-10-27 AT AT08843800T patent/ATE545634T1/de active
- 2008-10-27 WO PCT/CN2008/072840 patent/WO2009056070A1/zh not_active Ceased
- 2008-10-27 US US12/681,623 patent/US8350033B2/en active Active - Reinstated
- 2008-10-27 EP EP08843800A patent/EP2213666B1/en active Active
- 2008-10-27 JP JP2010530261A patent/JP5265691B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN101143851A (zh) | 2008-03-19 |
| EP2213666A1 (en) | 2010-08-04 |
| EP2213666A4 (en) | 2010-11-17 |
| ATE545634T1 (de) | 2012-03-15 |
| WO2009056070A1 (en) | 2009-05-07 |
| US8350033B2 (en) | 2013-01-08 |
| JP2011500736A (ja) | 2011-01-06 |
| CN101143851B (zh) | 2010-07-21 |
| EP2213666B1 (en) | 2012-02-15 |
| US20100228029A1 (en) | 2010-09-09 |
| ES2382979T3 (es) | 2012-06-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5265691B2 (ja) | リグストラジン芳香族酸エーテル類化合物、生成方法と薬物化合物及び応用 | |
| CA2584507C (en) | Flavanoids and isoflavanoids for the prevention and treatment of cardiovascular diseases | |
| JP5236664B2 (ja) | 心血管疾患を予防および治療するための化合物 | |
| JP2011500736A5 (https=) | ||
| CN116082303A (zh) | 新型氧代吡啶类化合物及其中间体和应用 | |
| KR20210082466A (ko) | 샤페론-매개 자가포식작용 조절제로서 유용한 벤족사졸 및 관련된 화합물 | |
| CN111518031A (zh) | 一种含有异羟肟酸的化合物及其制备方法、应用 | |
| CN100586937C (zh) | 川芎嗪茋类衍生物、制备方法和药物组合物与应用 | |
| AU2016317968B2 (en) | Compound having effect of inhibiting platelet aggregation and salt thereof, and composition for preventing or treating thrombotic diseases, containing same | |
| US20060058346A1 (en) | Novel enantiomers of etrahydroisoquinoline derivatives and theirpharmaceutically acceptable salts, their preparations and pharmaceutical compositions | |
| CN106146413B (zh) | 2,4-(1h,3h)-喹唑啉二酮衍生物及其合成方法和用途 | |
| CN101851209B (zh) | 咪唑乙基香草酸醚、其制备方法及其医药用途 | |
| JPH03218346A (ja) | テトラヒドロナフタレン誘導体、その製法並びにその合成中間体 | |
| CN101812025B (zh) | 吡嗪芳酸醚类化合物、制备方法和医药应用 | |
| CN102250099B (zh) | 一类非肽类抗凝血酶抑制剂、其制法以及医药用途 | |
| CN102786484B (zh) | 川芎嗪甲酰氧基肉桂酸类衍生物及其制备方法与应用 | |
| CN101541780A (zh) | 贝特羧酸酯类化合物及其制备方法和用途 | |
| Du et al. | Synthesis and biological evaluation of 2, 2-dimethylbenzopyran derivatives as potent neuroprotection agents | |
| US20130059882A1 (en) | 8-Phenylisoquinolines And Pharmaceutical Composition Used In Treatment For Sepsis | |
| CN106831437B (zh) | 含硝基乙烯基的酯类化合物及其制备方法和应用 | |
| CN107162913B (zh) | 一类新型氘代苯丙酸衍生物、其制备方法及其作为药物的用途 | |
| JP3220225B2 (ja) | グアニジノフェノール誘導体 | |
| CN103539760B (zh) | 苯氧苯乙酸类内皮素拮抗剂及其制备方法与应用 | |
| US7456205B2 (en) | Benzopyran compounds, process for preparing the same and their use | |
| KR820001449B1 (ko) | 퀴나졸린 유도체의 제조방법 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20120821 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20121121 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130212 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20130314 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20130409 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20130501 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5265691 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |