UA81246C2 - Salts of mandelic acid derivatives - Google Patents
Salts of mandelic acid derivatives Download PDFInfo
- Publication number
- UA81246C2 UA81246C2 UA20041109441A UA20041109441A UA81246C2 UA 81246 C2 UA81246 C2 UA 81246C2 UA 20041109441 A UA20041109441 A UA 20041109441A UA 20041109441 A UA20041109441 A UA 20041109441A UA 81246 C2 UA81246 C2 UA 81246C2
- Authority
- UA
- Ukraine
- Prior art keywords
- acid
- compound
- salt according
- compounds
- addition salt
- Prior art date
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- 150000003839 salts Chemical class 0.000 title claims abstract description 120
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical class O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 203
- 239000002253 acid Substances 0.000 claims abstract description 47
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 108090000190 Thrombin Proteins 0.000 claims abstract description 11
- 229960004072 thrombin Drugs 0.000 claims abstract description 11
- 230000005764 inhibitory process Effects 0.000 claims abstract description 6
- 238000000034 method Methods 0.000 claims description 53
- 238000002425 crystallisation Methods 0.000 claims description 39
- 230000008025 crystallization Effects 0.000 claims description 39
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims description 29
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 claims description 18
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 17
- 229910052731 fluorine Inorganic materials 0.000 claims description 17
- 239000011737 fluorine Substances 0.000 claims description 17
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 claims description 13
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 13
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 13
- 229940077388 benzenesulfonate Drugs 0.000 claims description 10
- 238000002441 X-ray diffraction Methods 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 239000000843 powder Substances 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000002671 adjuvant Substances 0.000 claims description 4
- QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- XTEGVFVZDVNBPF-UHFFFAOYSA-N naphthalene-1,5-disulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-N 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000000654 additive Substances 0.000 claims 4
- 230000000996 additive effect Effects 0.000 claims 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 abstract description 5
- 239000003112 inhibitor Substances 0.000 abstract description 4
- 239000000651 prodrug Substances 0.000 abstract description 3
- 229940002612 prodrug Drugs 0.000 abstract description 3
- 102100027612 Kallikrein-11 Human genes 0.000 abstract description 2
- 101710152431 Trypsin-like protease Proteins 0.000 abstract description 2
- 230000002860 competitive effect Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 148
- 239000000243 solution Substances 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 65
- 239000000203 mixture Substances 0.000 description 63
- 229940126062 Compound A Drugs 0.000 description 58
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 58
- 239000002904 solvent Substances 0.000 description 58
- 235000019439 ethyl acetate Nutrition 0.000 description 53
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- 238000005481 NMR spectroscopy Methods 0.000 description 41
- 238000002360 preparation method Methods 0.000 description 38
- 239000013078 crystal Substances 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 229960004592 isopropanol Drugs 0.000 description 29
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 27
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 26
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 26
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 26
- 229910052938 sodium sulfate Inorganic materials 0.000 description 26
- 235000011152 sodium sulphate Nutrition 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000005859 coupling reaction Methods 0.000 description 24
- 238000010168 coupling process Methods 0.000 description 23
- 239000011541 reaction mixture Substances 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
- 239000000126 substance Substances 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 19
- -1 amidine compounds Chemical class 0.000 description 19
- 230000008878 coupling Effects 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 239000002002 slurry Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000012296 anti-solvent Substances 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 150000007513 acids Chemical class 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- 239000012267 brine Substances 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 238000000113 differential scanning calorimetry Methods 0.000 description 11
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 9
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 9
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 9
- 230000008018 melting Effects 0.000 description 9
- 238000002844 melting Methods 0.000 description 9
- 239000004472 Lysine Substances 0.000 description 8
- 229940011051 isopropyl acetate Drugs 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 229960003646 lysine Drugs 0.000 description 8
- 238000010899 nucleation Methods 0.000 description 8
- 239000012071 phase Substances 0.000 description 8
- 230000007958 sleep Effects 0.000 description 8
- 238000010561 standard procedure Methods 0.000 description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 7
- 230000008901 benefit Effects 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 239000012265 solid product Substances 0.000 description 7
- 238000002411 thermogravimetry Methods 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- QDHFHIQKOVNCNC-UHFFFAOYSA-M butane-1-sulfonate Chemical compound CCCCS([O-])(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-M 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- ZGLUKQQSWABKDH-UHFFFAOYSA-N 5-amino-1-methyl-3h-indol-2-one Chemical compound NC1=CC=C2N(C)C(=O)CC2=C1 ZGLUKQQSWABKDH-UHFFFAOYSA-N 0.000 description 5
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 5
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 5
- 229940022663 acetate Drugs 0.000 description 5
- 125000005233 alkylalcohol group Chemical group 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 239000004220 glutamic acid Substances 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
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- 239000000463 material Substances 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 238000000634 powder X-ray diffraction Methods 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 238000000859 sublimation Methods 0.000 description 5
- 230000008022 sublimation Effects 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 201000005665 thrombophilia Diseases 0.000 description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 238000012565 NMR experiment Methods 0.000 description 4
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
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- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 239000003146 anticoagulant agent Substances 0.000 description 4
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- 238000001816 cooling Methods 0.000 description 4
- 238000007429 general method Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- XTEGVFVZDVNBPF-UHFFFAOYSA-L naphthalene-1,5-disulfonate(2-) Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1S([O-])(=O)=O XTEGVFVZDVNBPF-UHFFFAOYSA-L 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 238000011321 prophylaxis Methods 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 239000003868 thrombin inhibitor Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 230000009466 transformation Effects 0.000 description 4
- BJENCCAVAIAGOF-UHFFFAOYSA-N 3-chloro-5-hydroxybenzaldehyde Chemical compound OC1=CC(Cl)=CC(C=O)=C1 BJENCCAVAIAGOF-UHFFFAOYSA-N 0.000 description 3
- SFWWGMKXCYLZEG-UHFFFAOYSA-N 3-methylmorpholine Chemical compound CC1COCCN1 SFWWGMKXCYLZEG-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 239000004475 Arginine Substances 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
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- 241000124008 Mammalia Species 0.000 description 3
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
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- 238000002399 angioplasty Methods 0.000 description 3
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- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 239000000174 gluconic acid Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229960005337 lysine hydrochloride Drugs 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- 239000001630 malic acid Substances 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
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- 238000001757 thermogravimetry curve Methods 0.000 description 3
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- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0201661A SE0201661D0 (sv) | 2002-05-31 | 2002-05-31 | New salts |
| PCT/SE2003/000859 WO2003101957A1 (en) | 2002-05-31 | 2003-05-27 | New salts |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA81246C2 true UA81246C2 (en) | 2007-12-25 |
Family
ID=20288039
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA20041109441A UA81246C2 (en) | 2002-05-31 | 2003-05-27 | Salts of mandelic acid derivatives |
Country Status (31)
| Country | Link |
|---|---|
| US (2) | US7273858B2 (de) |
| EP (2) | EP2055696A1 (de) |
| JP (1) | JP4541140B2 (de) |
| KR (1) | KR20050009726A (de) |
| CN (2) | CN101735131A (de) |
| AR (1) | AR039937A1 (de) |
| AT (1) | ATE425963T1 (de) |
| AU (1) | AU2003232871B2 (de) |
| BR (1) | BR0311365A (de) |
| CA (1) | CA2487509A1 (de) |
| CY (1) | CY1109085T1 (de) |
| DE (1) | DE60326720D1 (de) |
| DK (1) | DK1513806T3 (de) |
| ES (1) | ES2322048T3 (de) |
| HK (1) | HK1073102A1 (de) |
| IL (1) | IL165295A0 (de) |
| IS (1) | IS7598A (de) |
| MX (1) | MXPA04011912A (de) |
| MY (1) | MY133333A (de) |
| NO (1) | NO329064B1 (de) |
| NZ (2) | NZ554323A (de) |
| PL (1) | PL373794A1 (de) |
| PT (1) | PT1513806E (de) |
| RU (2) | RU2345064C2 (de) |
| SA (1) | SA03240440B1 (de) |
| SE (1) | SE0201661D0 (de) |
| SI (1) | SI1513806T1 (de) |
| TW (2) | TWI313173B (de) |
| UA (1) | UA81246C2 (de) |
| WO (1) | WO2003101957A1 (de) |
| ZA (1) | ZA200409228B (de) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR035216A1 (es) * | 2000-12-01 | 2004-05-05 | Astrazeneca Ab | Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios |
| AR034517A1 (es) | 2001-06-21 | 2004-02-25 | Astrazeneca Ab | Formulacion farmaceutica |
| SE0201659D0 (sv) | 2002-05-31 | 2002-05-31 | Astrazeneca Ab | Modified release pharmaceutical formulation |
| SE0201661D0 (sv) * | 2002-05-31 | 2002-05-31 | Astrazeneca Ab | New salts |
| US7781424B2 (en) * | 2003-05-27 | 2010-08-24 | Astrazeneca Ab | Modified release pharmaceutical formulation |
| EP1732932B1 (de) * | 2004-04-09 | 2012-03-21 | Hanmi Holdings Co., Ltd. | Kristallines clopidogrelnaphthalinsulfonat oder hydrat davon, verfahren zu dessen herstellung und pharmazeutische zusammensetzung, die dieses enthält |
| ZA200608035B (en) * | 2004-04-20 | 2008-07-30 | Sanofi Aventis | Clopidogrel salt and polymorphic forms thereof |
| TW200827336A (en) * | 2006-12-06 | 2008-07-01 | Astrazeneca Ab | New crystalline forms |
| TW200900033A (en) * | 2007-06-21 | 2009-01-01 | Wen-Qing Li | Automatic brewing machine |
| US20090061000A1 (en) * | 2007-08-31 | 2009-03-05 | Astrazeneca Ab | Pharmaceutical formulation use 030 |
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| SE0201659D0 (sv) * | 2002-05-31 | 2002-05-31 | Astrazeneca Ab | Modified release pharmaceutical formulation |
| US7781424B2 (en) * | 2003-05-27 | 2010-08-24 | Astrazeneca Ab | Modified release pharmaceutical formulation |
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-
2002
- 2002-05-31 SE SE0201661A patent/SE0201661D0/xx unknown
-
2003
- 2003-05-27 AT AT03728206T patent/ATE425963T1/de not_active IP Right Cessation
- 2003-05-27 BR BR0311365-5A patent/BR0311365A/pt not_active IP Right Cessation
- 2003-05-27 CN CN200910260483A patent/CN101735131A/zh active Pending
- 2003-05-27 KR KR10-2004-7019439A patent/KR20050009726A/ko not_active Application Discontinuation
- 2003-05-27 NZ NZ554323A patent/NZ554323A/en not_active IP Right Cessation
- 2003-05-27 MX MXPA04011912A patent/MXPA04011912A/es active IP Right Grant
- 2003-05-27 AU AU2003232871A patent/AU2003232871B2/en not_active Ceased
- 2003-05-27 EP EP09151657A patent/EP2055696A1/de not_active Withdrawn
- 2003-05-27 PL PL03373794A patent/PL373794A1/xx not_active Application Discontinuation
- 2003-05-27 PT PT03728206T patent/PT1513806E/pt unknown
- 2003-05-27 EP EP03728206A patent/EP1513806B1/de not_active Expired - Lifetime
- 2003-05-27 RU RU2004133388/04A patent/RU2345064C2/ru not_active IP Right Cessation
- 2003-05-27 NZ NZ536738A patent/NZ536738A/en not_active IP Right Cessation
- 2003-05-27 DE DE60326720T patent/DE60326720D1/de not_active Expired - Lifetime
- 2003-05-27 CA CA002487509A patent/CA2487509A1/en not_active Abandoned
- 2003-05-27 CN CNA038124912A patent/CN1656067A/zh active Pending
- 2003-05-27 UA UA20041109441A patent/UA81246C2/uk unknown
- 2003-05-27 US US10/516,422 patent/US7273858B2/en not_active Expired - Fee Related
- 2003-05-27 IL IL16529503A patent/IL165295A0/xx unknown
- 2003-05-27 ES ES03728206T patent/ES2322048T3/es not_active Expired - Lifetime
- 2003-05-27 JP JP2004509651A patent/JP4541140B2/ja not_active Expired - Fee Related
- 2003-05-27 SI SI200331578T patent/SI1513806T1/sl unknown
- 2003-05-27 WO PCT/SE2003/000859 patent/WO2003101957A1/en active Application Filing
- 2003-05-27 DK DK03728206T patent/DK1513806T3/da active
- 2003-05-29 MY MYPI20031981A patent/MY133333A/en unknown
- 2003-05-30 AR ARP030101935A patent/AR039937A1/es unknown
- 2003-05-30 TW TW092114807A patent/TWI313173B/zh active
- 2003-05-30 TW TW097151265A patent/TWI367754B/zh not_active IP Right Cessation
- 2003-12-10 SA SA3240440A patent/SA03240440B1/ar unknown
-
2004
- 2004-11-09 NO NO20044867A patent/NO329064B1/no not_active IP Right Cessation
- 2004-11-17 ZA ZA200409228A patent/ZA200409228B/en unknown
- 2004-12-15 IS IS7598A patent/IS7598A/is unknown
-
2005
- 2005-06-20 HK HK05105118.1A patent/HK1073102A1/xx not_active IP Right Cessation
-
2007
- 2007-08-16 US US11/839,842 patent/US7763597B2/en not_active Expired - Fee Related
-
2008
- 2008-07-09 RU RU2008127541/04A patent/RU2008127541A/ru not_active Application Discontinuation
-
2009
- 2009-05-20 CY CY20091100535T patent/CY1109085T1/el unknown
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