CA2680604C - Forme triol de rosuvastatine - Google Patents

Forme triol de rosuvastatine Download PDF

Info

Publication number: CA2680604C
Authority: CA; Canada
Prior art keywords: rosuvastatin; triol; ester; calcium; diol
Prior art date: 2007-03-13
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2680604A

Other languages

English (en)

Other versions

CA2680604A1 (fr

Inventor

Valerie Niddam-Hildesheim

Anna Balanov

Irena Veinberg

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Teva Pharmaceutical Industries Ltd

Original Assignee

Teva Pharmaceutical Industries Ltd

Priority date (The priority date 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 date listed.)

2007-03-13

Filing date

2008-03-13

Publication date

2012-08-07

2008-03-13 Application filed by Teva Pharmaceutical Industries Ltd filed Critical Teva Pharmaceutical Industries Ltd

2008-09-18 Publication of CA2680604A1 publication Critical patent/CA2680604A1/fr

2012-08-07 Application granted granted Critical

2012-08-07 Publication of CA2680604C publication Critical patent/CA2680604C/fr

Status Expired - Fee Related legal-status Critical Current

2028-03-13 Anticipated expiration legal-status Critical

Links

229960000672 rosuvastatin Drugs 0.000 title claims abstract description 274
BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 title claims abstract description 160
150000004072 triols Chemical group 0.000 title claims description 5
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical compound ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 claims abstract description 134
-1 rosuvastatin diol Chemical class 0.000 claims description 139
239000011575 calcium Substances 0.000 claims description 64
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 62
229910052791 calcium Inorganic materials 0.000 claims description 61
238000000034 method Methods 0.000 claims description 57
230000014759 maintenance of location Effects 0.000 claims description 56
239000002253 acid Substances 0.000 claims description 53
238000004128 high performance liquid chromatography Methods 0.000 claims description 49
150000002148 esters Chemical group 0.000 claims description 48
239000000203 mixture Substances 0.000 claims description 37
239000012535 impurity Substances 0.000 claims description 35
230000008569 process Effects 0.000 claims description 32
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 29
238000012360 testing method Methods 0.000 claims description 28
150000001875 compounds Chemical class 0.000 claims description 27
239000003550 marker Substances 0.000 claims description 27
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 25
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
239000003960 organic solvent Substances 0.000 claims description 20
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
150000002009 diols Chemical class 0.000 claims description 19
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 18
150000002596 lactones Chemical group 0.000 claims description 17
239000011541 reaction mixture Substances 0.000 claims description 17
LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical group [Ca+2].CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O.CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 claims description 17
229960004796 rosuvastatin calcium Drugs 0.000 claims description 15
238000004519 manufacturing process Methods 0.000 claims description 14
150000003839 salts Chemical group 0.000 claims description 14
239000002585 base Substances 0.000 claims description 13
150000001342 alkaline earth metals Chemical class 0.000 claims description 11
229910000085 borane Inorganic materials 0.000 claims description 11
159000000007 calcium salts Chemical class 0.000 claims description 11
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
150000001768 cations Chemical class 0.000 claims description 9
239000008194 pharmaceutical composition Substances 0.000 claims description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
239000003513 alkali Substances 0.000 claims description 8
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
239000001110 calcium chloride Substances 0.000 claims description 6
229910001628 calcium chloride Inorganic materials 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
230000003301 hydrolyzing effect Effects 0.000 claims description 6
229910052751 metal Inorganic materials 0.000 claims description 6
239000002184 metal Substances 0.000 claims description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical group OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 5
229910052783 alkali metal Inorganic materials 0.000 claims description 5
150000001340 alkali metals Chemical class 0.000 claims description 5
150000007529 inorganic bases Chemical class 0.000 claims description 5
150000002978 peroxides Chemical class 0.000 claims description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical group [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 4
BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 4
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 4
235000011114 ammonium hydroxide Nutrition 0.000 claims description 4
229910001424 calcium ion Inorganic materials 0.000 claims description 4
FODOUIXGKGNSMR-UHFFFAOYSA-L magnesium;2-oxidooxycarbonylbenzoate;hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[O-]OC(=O)C1=CC=CC=C1C([O-])=O FODOUIXGKGNSMR-UHFFFAOYSA-L 0.000 claims description 4
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical group CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 claims description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
SOEGVMSNJOCVHT-VEUZHWNKSA-N Rosuvastatin lactone Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC(N(C)S(C)(=O)=O)=NC=1C1=CC=C(F)C=C1 SOEGVMSNJOCVHT-VEUZHWNKSA-N 0.000 claims description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
230000001590 oxidative effect Effects 0.000 claims description 3
150000002500 ions Chemical class 0.000 claims description 2
235000011149 sulphuric acid Nutrition 0.000 claims description 2
238000000746 purification Methods 0.000 claims 5
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 claims 3
239000000725 suspension Substances 0.000 claims 1
238000004458 analytical method Methods 0.000 abstract description 2
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
239000003480 eluent Substances 0.000 description 20
239000000243 solution Substances 0.000 description 20
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
239000006227 byproduct Substances 0.000 description 7
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 6
239000012071 phase Substances 0.000 description 6
238000004451 qualitative analysis Methods 0.000 description 6
230000004044 response Effects 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
108010007622 LDL Lipoproteins Proteins 0.000 description 5
102000007330 LDL Lipoproteins Human genes 0.000 description 5
235000011148 calcium chloride Nutrition 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
159000000000 sodium salts Chemical class 0.000 description 5
238000003756 stirring Methods 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
239000008186 active pharmaceutical agent Substances 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
230000009467 reduction Effects 0.000 description 4
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
238000004809 thin layer chromatography Methods 0.000 description 4
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 3
239000012267 brine Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
235000012000 cholesterol Nutrition 0.000 description 3
239000003814 drug Substances 0.000 description 3
239000007789 gas Substances 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
239000000463 material Substances 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
238000004445 quantitative analysis Methods 0.000 description 3
238000000926 separation method Methods 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000000126 substance Substances 0.000 description 3
238000000825 ultraviolet detection Methods 0.000 description 3
ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 2
CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 2
XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 2
208000035150 Hypercholesterolemia Diseases 0.000 description 2
208000031226 Hyperlipidaemia Diseases 0.000 description 2
PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 2
RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
239000000908 ammonium hydroxide Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
229960005370 atorvastatin Drugs 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
229960005110 cerivastatin Drugs 0.000 description 2
SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 2
229940066901 crestor Drugs 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000001035 drying Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
229960003765 fluvastatin Drugs 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
229960004844 lovastatin Drugs 0.000 description 2
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 2
QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
239000002245 particle Substances 0.000 description 2
229960002965 pravastatin Drugs 0.000 description 2
TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
238000012545 processing Methods 0.000 description 2
238000011002 quantification Methods 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229960002855 simvastatin Drugs 0.000 description 2
RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
235000010265 sodium sulphite Nutrition 0.000 description 2
KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 1
IKAACYWAXDLDPM-UHFFFAOYSA-N 1,2,3,4,4a,5-hexahydronaphthalene Chemical group C1=CCC2CCCCC2=C1 IKAACYWAXDLDPM-UHFFFAOYSA-N 0.000 description 1
FFRUQSUMDFNBLG-UHFFFAOYSA-N 2-(2,4,5-trichlorophenoxy)ethyl 2,2,2-trichloroacetate Chemical compound ClC1=CC(Cl)=C(OCCOC(=O)C(Cl)(Cl)Cl)C=C1Cl FFRUQSUMDFNBLG-UHFFFAOYSA-N 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
208000024172 Cardiovascular disease Diseases 0.000 description 1
KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 1
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
108010028554 LDL Cholesterol Proteins 0.000 description 1
102000000853 LDL receptors Human genes 0.000 description 1
108010001831 LDL receptors Proteins 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
208000021642 Muscular disease Diseases 0.000 description 1
201000009623 Myopathy Diseases 0.000 description 1
108090000854 Oxidoreductases Proteins 0.000 description 1
102000004316 Oxidoreductases Human genes 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
238000013459 approach Methods 0.000 description 1
230000008901 benefit Effects 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
230000007073 chemical hydrolysis Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
208000029078 coronary artery disease Diseases 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000001514 detection method Methods 0.000 description 1
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
FESAXEDIWWXCNG-UHFFFAOYSA-N diethyl(methoxy)borane Chemical compound CCB(CC)OC FESAXEDIWWXCNG-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000007071 enzymatic hydrolysis Effects 0.000 description 1
238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
238000013213 extrapolation Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
229910000040 hydrogen fluoride Inorganic materials 0.000 description 1
150000001261 hydroxy acids Chemical class 0.000 description 1
208000020346 hyperlipoproteinemia Diseases 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
238000007273 lactonization reaction Methods 0.000 description 1
230000003902 lesion Effects 0.000 description 1
150000002632 lipids Chemical class 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
WOCOTUDOVSLFOB-UHFFFAOYSA-N n-[4-(4-fluorophenyl)-5-formyl-6-propan-2-ylpyrimidin-2-yl]-n-methylmethanesulfonamide Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1C=O WOCOTUDOVSLFOB-UHFFFAOYSA-N 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
238000000053 physical method Methods 0.000 description 1
229960002797 pitavastatin Drugs 0.000 description 1
VGYFMXBACGZSIL-MCBHFWOFSA-N pitavastatin Chemical compound OC(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 VGYFMXBACGZSIL-MCBHFWOFSA-N 0.000 description 1
238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
238000009790 rate-determining step (RDS) Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000001448 refractive index detection Methods 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
239000007787 solid Substances 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
238000000357 thermal conductivity detection Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Hematology (AREA)
Diabetes (AREA)
Obesity (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Investigating Or Analysing Biological Materials (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Plural Heterocyclic Compounds (AREA)

CA2680604A 2007-03-13 2008-03-13 Forme triol de rosuvastatine Expired - Fee Related CA2680604C (fr)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US90691407P	2007-03-13	2007-03-13
US60/906,914		2007-03-13
US91846607P	2007-03-15	2007-03-15
US60/918,466		2007-03-15
PCT/US2008/003470 WO2008112317A2 (fr)	2007-03-13	2008-03-13	Forme triol de rosuvastatine

Publications (2)

Publication Number	Publication Date
CA2680604A1 CA2680604A1 (fr)	2008-09-18
CA2680604C true CA2680604C (fr)	2012-08-07

Family

ID=39650560

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2680604A Expired - Fee Related CA2680604C (fr)	2007-03-13	2008-03-13	Forme triol de rosuvastatine

Country Status (8)

Country	Link
EP (1)	EP2121631A2 (fr)
JP (1)	JP5330225B2 (fr)
KR (1)	KR100945760B1 (fr)
BR (1)	BRPI0803085A2 (fr)
CA (1)	CA2680604C (fr)
IL (1)	IL200449A0 (fr)
MX (1)	MX2008014552A (fr)
WO (1)	WO2008112317A2 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP2576518B1 (fr) *	2010-06-07	2016-08-10	Pharmathen S.A.	Procédé amélioré pour la préparation d'intermédiaire propénal et dérivés de celui-ci
CN112782333B (zh) *	2020-12-25	2022-07-12	石家庄四药有限公司	一种匹伐他汀异丙基叔丁酯非对映异构体的hplc检测方法

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN1894221B (zh) *	2003-12-02	2012-08-08	特瓦制药工业有限公司	用于表征罗苏伐他汀的参照标准品

2008
- 2008-03-13 JP JP2009504512A patent/JP5330225B2/ja not_active Expired - Fee Related
- 2008-03-13 BR BRPI0803085-5A patent/BRPI0803085A2/pt not_active IP Right Cessation
- 2008-03-13 MX MX2008014552A patent/MX2008014552A/es active IP Right Grant
- 2008-03-13 WO PCT/US2008/003470 patent/WO2008112317A2/fr not_active Ceased
- 2008-03-13 KR KR1020087027688A patent/KR100945760B1/ko not_active Expired - Fee Related
- 2008-03-13 CA CA2680604A patent/CA2680604C/fr not_active Expired - Fee Related
- 2008-03-13 EP EP08726880A patent/EP2121631A2/fr not_active Withdrawn
2009
- 2009-08-18 IL IL200449A patent/IL200449A0/en unknown

Also Published As

Publication number	Publication date
EP2121631A2 (fr)	2009-11-25
WO2008112317A2 (fr)	2008-09-18
KR20090010195A (ko)	2009-01-29
CA2680604A1 (fr)	2008-09-18
KR100945760B1 (ko)	2010-03-08
WO2008112317A3 (fr)	2008-11-06
JP2009519353A (ja)	2009-05-14
IL200449A0 (en)	2010-04-29
JP5330225B2 (ja)	2013-10-30
BRPI0803085A2 (pt)	2011-08-30
MX2008014552A (es)	2009-03-09

Legal Events

Date	Code	Title	Description
2009-09-11	EEER	Examination request
2015-04-25	MKLA	Lapsed	Effective date: 20150313

Publication	Publication Date	Title
US7741482B2 (en)	2010-06-22	Reference standard for characterization of rosuvastatin
US7566782B2 (en)	2009-07-28	Process for the preparation of rosuvastatin
JP4996786B2 (ja)	2012-08-08	結晶質の化合物ビス［（ｅ）−７−［４−（４−フルオロフェニル）−６−イソプロピル−２−［メチル（メチルスルホニル）アミノ］ピリミジン−５−イル］（３ｒ，５ｓ）−３，５−ジヒドロキシ−６−ヘプテン酸］カルシウム塩
MX2007010138A (es)	2007-09-27	Preparacion de rosuvastatina.
US20070037979A1 (en)	2007-02-15	Preparation of rosuvastatin
CA2680604C (fr)	2012-08-07	Forme triol de rosuvastatine
CA2725052C (fr)	2014-09-16	Procede de preparation de la rosuvastatine calcique et de ses intermediaires
US7851624B2 (en)	2010-12-14	Triol form of rosuvastatin and synthesis of rosuvastatin
JP2010501643A (ja)	2010-01-21	薄膜蒸発及び化学的手法によるロスバスタチン中間体の精製
WO2010029561A1 (fr)	2010-03-18	Procédé de préparation d’acétonide de rosuvastatine calcique
CN101631777A (zh)	2010-01-20	罗苏伐他汀的三醇形式
CN107382875A (zh)	2017-11-24	一种瑞舒伐他汀钙手性异构体杂质的合成方法
Schneider et al.	1989	Determination of the new monoamine oxidase inhibitor brofaromine and its major metabolite in biological material by gas chromatography with electron-capture detection