NO323770B1 - Krystallinske salter av 7-[4-(fluorfenyl)-6-isopropyl-2-[metyl(metylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroksyhept-6-ensyre, farmasoytisk blanding inneholdende disse, fremgangsmate for fremstilling samt anvendelse av disse for fremstilling av amorft kalsiumsalt og medikament. - Google Patents
Krystallinske salter av 7-[4-(fluorfenyl)-6-isopropyl-2-[metyl(metylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroksyhept-6-ensyre, farmasoytisk blanding inneholdende disse, fremgangsmate for fremstilling samt anvendelse av disse for fremstilling av amorft kalsiumsalt og medikament. Download PDFInfo
- Publication number
- NO323770B1 NO323770B1 NO20023853A NO20023853A NO323770B1 NO 323770 B1 NO323770 B1 NO 323770B1 NO 20023853 A NO20023853 A NO 20023853A NO 20023853 A NO20023853 A NO 20023853A NO 323770 B1 NO323770 B1 NO 323770B1
- Authority
- NO
- Norway
- Prior art keywords
- crystalline
- fluorophenyl
- amino
- dihydroxyhept
- isopropyl
- Prior art date
Links
- 150000003839 salts Chemical class 0.000 title claims description 51
- 159000000007 calcium salts Chemical class 0.000 title claims description 13
- 238000000034 method Methods 0.000 title claims description 8
- 238000002360 preparation method Methods 0.000 title claims description 8
- 239000003814 drug Substances 0.000 title claims description 4
- -1 7- [4- (fluorophenyl) -6-isopropyl-2- [methyl (methylsulfonyl) amino] pyrimidin-5-yl] - (3R, 5S) -3,5-dihydroxyhept-6-enoic acid Chemical class 0.000 title claims description 3
- 239000008194 pharmaceutical composition Chemical class 0.000 title claims description 3
- 229940079593 drug Drugs 0.000 title description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 66
- 239000000243 solution Substances 0.000 claims description 45
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 31
- 238000001228 spectrum Methods 0.000 claims description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 16
- 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 claims description 15
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical class NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 13
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 10
- 238000002441 X-ray diffraction Methods 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 8
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 claims description 6
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical class CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 5
- BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 claims description 5
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical class NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims description 5
- DRDCQJADRSJFFD-UHFFFAOYSA-N tris-hydroxymethyl-methyl-ammonium Chemical compound OC[N+](C)(CO)CO DRDCQJADRSJFFD-UHFFFAOYSA-N 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 150000003863 ammonium salts Chemical class 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 229910003002 lithium salt Inorganic materials 0.000 claims description 3
- 159000000002 lithium salts Chemical class 0.000 claims description 3
- 159000000003 magnesium salts Chemical class 0.000 claims description 3
- MMTXSCWTVRMIIY-UHFFFAOYSA-N 3,5-dihydroxyhept-6-enoic acid Chemical compound OC(=O)CC(O)CC(O)C=C MMTXSCWTVRMIIY-UHFFFAOYSA-N 0.000 claims description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-O benzylaminium Chemical compound [NH3+]CC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-O 0.000 claims description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-O ethylaminium Chemical compound CC[NH3+] QUSNBJAOOMFDIB-UHFFFAOYSA-O 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 229910052749 magnesium Inorganic materials 0.000 claims 1
- 239000011777 magnesium Substances 0.000 claims 1
- 239000008024 pharmaceutical diluent Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 62
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- 239000008346 aqueous phase Substances 0.000 description 12
- 239000013078 crystal Substances 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 7
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000012258 stirred mixture Substances 0.000 description 4
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 238000001816 cooling Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 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 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VHOQHIIPURUXMN-DHMAKVBVSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoic acid;methanamine Chemical compound NC.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 VHOQHIIPURUXMN-DHMAKVBVSA-N 0.000 description 2
- YURNCBVQZBJDAJ-UHFFFAOYSA-N 2-heptenoic acid Chemical compound CCCCC=CC(O)=O YURNCBVQZBJDAJ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- 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 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- CGRKYEALWSRNJS-UHFFFAOYSA-N sodium;2-methylbutan-2-olate Chemical compound [Na+].CCC(C)(C)[O-] CGRKYEALWSRNJS-UHFFFAOYSA-N 0.000 description 2
- BPRHUIZQVSMCRT-IAGOWNOFSA-N (3R,5S)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-yl-5-pyrimidinyl]-3,5-dihydroxy-6-heptenoic acid Chemical class CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1C=C[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-IAGOWNOFSA-N 0.000 description 1
- DARGBXLSUYBWAR-DHMAKVBVSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate;(4-methoxyphenyl)methylazanium Chemical compound COC1=CC=C(C[NH3+])C=C1.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 DARGBXLSUYBWAR-DHMAKVBVSA-N 0.000 description 1
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- WZEMSIKSCALWJZ-UHFFFAOYSA-N azane;ethanol Chemical compound N.CCO.CCO WZEMSIKSCALWJZ-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- MYLFPPBEZAVKTB-DHMAKVBVSA-N benzylazanium;(e,3r,5s)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate Chemical compound [NH3+]CC1=CC=CC=C1.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 MYLFPPBEZAVKTB-DHMAKVBVSA-N 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229960002713 calcium chloride Drugs 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 1
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- JCRCPEDXAHDCAJ-UHFFFAOYSA-N ethoxy(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(OCC)C1=CC=CC=C1 JCRCPEDXAHDCAJ-UHFFFAOYSA-N 0.000 description 1
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000001282 iso-butane Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
- 150000002680 magnesium Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- RCDJQJJKUZFBGO-BGRFNVSISA-L magnesium;(e,3r,5s)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate Chemical compound [Mg+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 RCDJQJJKUZFBGO-BGRFNVSISA-L 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- RMYXELUYVYVDAI-UHFFFAOYSA-N methyl 2-amino-4-(4-fluorophenyl)-6-propan-2-ylpyrimidine-5-carboxylate Chemical compound COC(=O)C1=C(C(C)C)N=C(N)N=C1C1=CC=C(F)C=C1 RMYXELUYVYVDAI-UHFFFAOYSA-N 0.000 description 1
- BYVHIGJQQZGFPU-UHFFFAOYSA-N methyl 4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidine-5-carboxylate Chemical compound COC(=O)C1=C(C(C)C)N=C(N(C)S(C)(=O)=O)N=C1C1=CC=C(F)C=C1 BYVHIGJQQZGFPU-UHFFFAOYSA-N 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- CVRDGWDBQZPJJI-UHFFFAOYSA-N n-[5-(diphenylphosphorylmethyl)-4-(4-fluorophenyl)-6-propan-2-ylpyrimidin-2-yl]-n-methylmethanesulfonamide Chemical compound C=1C=CC=CC=1P(=O)(C=1C=CC=CC=1)CC=1C(C(C)C)=NC(N(C)S(C)(=O)=O)=NC=1C1=CC=C(F)C=C1 CVRDGWDBQZPJJI-UHFFFAOYSA-N 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- RGEBGDYYHAFODH-DHMAKVBVSA-M sodium;(e,3r,5s)-7-[4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidin-5-yl]-3,5-dihydroxyhept-6-enoate Chemical compound [Na+].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 RGEBGDYYHAFODH-DHMAKVBVSA-M 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- JEFQIIXBSQLRTF-ZJUUUORDSA-N tert-butyl 2-[(4r,6s)-6-formyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate Chemical compound CC(C)(C)OC(=O)C[C@H]1C[C@@H](C=O)OC(C)(C)O1 JEFQIIXBSQLRTF-ZJUUUORDSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- 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)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0003305.0A GB0003305D0 (en) | 2000-02-15 | 2000-02-15 | Pyrimidine derivatives |
| PCT/GB2001/000574 WO2001060804A1 (en) | 2000-02-15 | 2001-02-12 | Crystalline salts of 7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3r,5s)-3,5-dihydroxyhept-6-enoic acid |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20023853L NO20023853L (no) | 2002-08-14 |
| NO20023853D0 NO20023853D0 (no) | 2002-08-14 |
| NO323770B1 true NO323770B1 (no) | 2007-07-02 |
Family
ID=9885517
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20023853A NO323770B1 (no) | 2000-02-15 | 2002-08-14 | Krystallinske salter av 7-[4-(fluorfenyl)-6-isopropyl-2-[metyl(metylsulfonyl)amino]pyrimidin-5-yl]-(3R,5S)-3,5-dihydroksyhept-6-ensyre, farmasoytisk blanding inneholdende disse, fremgangsmate for fremstilling samt anvendelse av disse for fremstilling av amorft kalsiumsalt og medikament. |
Country Status (36)
| Country | Link |
|---|---|
| US (2) | US6841554B2 (ja) |
| EP (2) | EP1873148B1 (ja) |
| JP (1) | JP4099333B2 (ja) |
| KR (1) | KR100708262B1 (ja) |
| CN (1) | CN1210266C (ja) |
| AR (1) | AR029228A1 (ja) |
| AT (2) | ATE449079T1 (ja) |
| AU (1) | AU775569B2 (ja) |
| BG (1) | BG65562B1 (ja) |
| BR (1) | BR0108378A (ja) |
| CA (1) | CA2397450C (ja) |
| CO (1) | CO5280213A1 (ja) |
| CY (2) | CY1107225T1 (ja) |
| CZ (1) | CZ302136B6 (ja) |
| DE (2) | DE60140581D1 (ja) |
| DK (2) | DK1263739T3 (ja) |
| EE (1) | EE05288B1 (ja) |
| ES (2) | ES2298214T3 (ja) |
| GB (1) | GB0003305D0 (ja) |
| HK (2) | HK1051532A1 (ja) |
| HU (1) | HU228422B1 (ja) |
| IL (2) | IL150807A0 (ja) |
| IS (1) | IS2592B (ja) |
| MX (1) | MXPA02007819A (ja) |
| MY (1) | MY129018A (ja) |
| NO (1) | NO323770B1 (ja) |
| NZ (1) | NZ520032A (ja) |
| PL (1) | PL206729B1 (ja) |
| PT (2) | PT1263739E (ja) |
| RU (1) | RU2265599C2 (ja) |
| SA (1) | SA01220166B1 (ja) |
| SI (2) | SI1873148T1 (ja) |
| SK (1) | SK287144B6 (ja) |
| UA (1) | UA74567C2 (ja) |
| WO (1) | WO2001060804A1 (ja) |
| ZA (1) | ZA200205331B (ja) |
Families Citing this family (56)
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|---|---|---|---|---|
| GB0003305D0 (en) | 2000-02-15 | 2000-04-05 | Zeneca Ltd | Pyrimidine derivatives |
| PL366831A1 (en) | 2001-07-13 | 2005-02-07 | Astrazeneca Uk Limited | Preparation of aminopyrimidine compounds |
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| CA2486557A1 (en) * | 2002-06-13 | 2003-12-24 | Novartis Ag | Calcium salts of indole derived statins |
| GB0218781D0 (en) | 2002-08-13 | 2002-09-18 | Astrazeneca Ab | Chemical process |
| NZ540722A (en) | 2002-12-16 | 2008-03-28 | Astrazeneca Uk Ltd | Process for the preparation of pyrimidine compounds and intermediates thereof |
| GB0312896D0 (en) * | 2003-06-05 | 2003-07-09 | Astrazeneca Ab | Chemical process |
| AU2003269478A1 (en) * | 2003-08-27 | 2005-03-16 | Hetero Drugs Limited | A novel process for amorphous rosuvastatin calcium |
| CA2537271A1 (en) | 2003-08-28 | 2005-03-17 | Teva Pharmaceutical Industries, Ltd. | Process for preparation of rosuvastatin calcium |
| UY28501A1 (es) * | 2003-09-10 | 2005-04-29 | Astrazeneca Uk Ltd | Compuestos químicos |
| GB0321827D0 (en) * | 2003-09-18 | 2003-10-15 | Astrazeneca Uk Ltd | Chemical compounds |
| GB0322552D0 (en) | 2003-09-26 | 2003-10-29 | Astrazeneca Uk Ltd | Therapeutic treatment |
| US20070191318A1 (en) * | 2003-10-22 | 2007-08-16 | Yatendra Kumar | Process for the preparation of amorphous rosuvastatin calcium |
| GB0324791D0 (en) | 2003-10-24 | 2003-11-26 | Astrazeneca Ab | Chemical process |
| WO2005051921A1 (en) * | 2003-11-24 | 2005-06-09 | Teva Pharmaceutical Industries Ltd. | Crystalline ammonium salts of rosuvastatin |
| ATE507209T1 (de) | 2003-12-02 | 2011-05-15 | Teva Pharma | Referenzstandard zur charakterisierung von rosuvastatin |
| EP1709008A1 (en) * | 2004-01-19 | 2006-10-11 | Ranbaxy Laboratories Limited | Salts of hmg-coa reductase inhibitors and use thereof |
| WO2005077917A1 (en) * | 2004-01-19 | 2005-08-25 | Ranbaxy Laboratories Limited | Amorphous salts of rosuvastatin |
| US7241800B2 (en) | 2004-03-17 | 2007-07-10 | Mai De Ltd. | Anhydrous amorphous form of fluvastatin sodium |
| GB0406757D0 (en) * | 2004-03-26 | 2004-04-28 | Avecia Ltd | Process and compounds |
| JP2007508379A (ja) | 2004-07-13 | 2007-04-05 | テバ ファーマシューティカル インダストリーズ リミティド | Ｔｅｍｐｏ媒介型酸化段階を包含するロスバスタチンの調製方法 |
| WO2006035277A2 (en) * | 2004-09-27 | 2006-04-06 | Ranbaxy Laboratories Limited | Novel processes for preparing amorphous rosuvastatin calcium and a novel polymorphic form of rosuvastatin sodium |
| GB0428328D0 (en) | 2004-12-24 | 2005-02-02 | Astrazeneca Uk Ltd | Chemical process |
| MX2007010138A (es) | 2005-02-22 | 2007-09-27 | Teva Pharma | Preparacion de rosuvastatina. |
| CA2499047A1 (en) * | 2005-03-01 | 2006-09-01 | Apotex Pharmachem Inc. | Process for producing atorvastatin hemicalcium |
| EP2508514B1 (en) | 2005-06-24 | 2017-10-18 | LEK Pharmaceuticals d.d. | Process for preparing amorphous rosuvastatin calcium free of impurities |
| US8207333B2 (en) | 2005-06-24 | 2012-06-26 | Lek Pharmaceuticals D. D. | Process for preparing pure amorphous rosuvastatin calcuim |
| EP1805148A2 (en) | 2005-08-16 | 2007-07-11 | Teva Pharmaceutical Industries Ltd. | Crystalline rosuvastatin intermediate |
| HU227696B1 (en) * | 2006-04-13 | 2011-12-28 | Egyt Gyogyszervegyeszeti Gyar | Zinc salt of rosuvastatin, process for its preparation and pharmaceutical compositions containing it |
| US8455640B2 (en) * | 2006-05-03 | 2013-06-04 | Msn Laboratories Limited | Process for statins and its pharmaceutically acceptable salts thereof |
| EP1948618A1 (en) | 2006-09-18 | 2008-07-30 | Teva Pharmaceutical Industries Ltd. | Crystalline rosuvastatin calcium |
| WO2008038132A1 (en) * | 2006-09-28 | 2008-04-03 | Aurobindo Pharma Limited | Crystalline diamine salts of rosuvastatin |
| EP2086945B1 (en) * | 2006-10-09 | 2016-01-06 | MSN Laboratories Private Limited | Novel process for the preparation of statins and their pharmaceutically acceptable salts thereof |
| WO2008067440A2 (en) * | 2006-11-29 | 2008-06-05 | Dr. Reddy's Laboratories Ltd. | Rosuvastatin dehydroabietylamine salt |
| HU230981B1 (hu) * | 2007-10-12 | 2019-08-28 | Egis Gyógyszergyár Nyilvánosan Működő Részvénytársaság | Eljárás rosuvastatin só előállítására |
| WO2009143776A1 (zh) | 2008-05-27 | 2009-12-03 | 常州制药厂有限公司 | 瑞舒伐他汀钙盐的制备方法及其中间体 |
| WO2010035284A2 (en) * | 2008-09-26 | 2010-04-01 | Matrix Laboratories Ltd | An improved process for the preparation of rosuvastatin calcium |
| EP2752407B1 (en) * | 2009-01-14 | 2015-09-23 | Krka Tovarna Zdravil, D.D., Novo Mesto | Crystalline rosuvastatin calcium trihydrate |
| WO2010082072A1 (en) | 2009-01-15 | 2010-07-22 | Egis Gyógyszergyár | Process for the preparation of rosuvastatin salts |
| WO2010089770A2 (en) | 2009-01-19 | 2010-08-12 | Msn Laboratories Limited | Improved process for the preparation of highly pure (3r,5s)-7-[2-cyclopropyl-4-(4-fluorophenyl) quinolin-3-yl]-3,5-dihydroxy-6(e)-heptenoic acid and pharmaceutically acceptable salts thereof |
| HUP0900285A2 (en) | 2009-05-07 | 2011-01-28 | Egis Gyogyszergyar Nyilvanosan Mukoedoe Reszvenytarsasag | Rosuvastatin salts and preparation thereof |
| WO2011086584A2 (en) | 2010-01-18 | 2011-07-21 | Msn Laboratories Limited | Improved process for the preparation of amide intermediates and their use thereof |
| CN101935304B (zh) * | 2010-06-22 | 2012-04-18 | 重庆博腾制药科技股份有限公司 | 瑞舒伐他汀甘氨酸叔丁酯盐及其制备方法 |
| WO2012063115A2 (en) | 2010-11-11 | 2012-05-18 | Jubilant Life Sciences Ltd. | Process for the preparation of rosuvastatin calcium via novel amine intermediate |
| HU230737B1 (hu) | 2010-11-16 | 2018-01-29 | EGIS Gyógyszergyár Nyrt | Eljárás rosuvastatin só előállítására |
| HU229260B1 (en) | 2010-11-29 | 2013-10-28 | Egis Gyogyszergyar Nyrt | Process for preparation of rosuvastatin salts |
| WO2012073256A1 (en) * | 2010-11-29 | 2012-06-07 | Cadila Healthcare Limited | Salts of rosuvastatin |
| HU230987B1 (hu) | 2010-11-29 | 2019-08-28 | Egis Gyógyszergyár Nyrt. | Eljárás nagy tisztaságú gyógyszeripari intermedierek előállítására |
| WO2012176218A1 (en) * | 2011-06-24 | 2012-12-27 | Ind-Swift Laboratories Limited | Process for preparing rosuvastatin calcium through novel amine salt |
| EP2602249B1 (en) * | 2011-12-06 | 2015-08-12 | F.I.S. Fabbrica Italiana Sintetici S.p.A. | Synthesis of rosuvastatin by means of co-crystals |
| US9695130B2 (en) | 2014-02-06 | 2017-07-04 | Api Corporation | Rosuvastatin calcium and process for producing intermediate thereof |
| CN106397335A (zh) * | 2016-08-31 | 2017-02-15 | 湖北祥云(集团)化工股份有限公司 | 瑞舒伐他汀中间体的制备方法 |
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| CN109651259B (zh) * | 2018-12-29 | 2020-05-19 | 浙江永太科技股份有限公司 | 一种瑞舒伐他汀钙关键中间体的纯化方法 |
| CN111454216B (zh) * | 2019-10-21 | 2021-06-29 | 山东理工职业学院 | HMG-CoA还原酶抑制剂及其中间体的制备方法 |
| CN115417824A (zh) * | 2022-09-21 | 2022-12-02 | 安徽美诺华药物化学有限公司 | 一种瑞舒伐他汀中间体的高纯度制备方法 |
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| GB0324791D0 (en) | 2003-10-24 | 2003-11-26 | Astrazeneca Ab | Chemical process |
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2000
- 2000-02-15 GB GBGB0003305.0A patent/GB0003305D0/en not_active Ceased
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2001
- 2001-02-12 ES ES01904167T patent/ES2298214T3/es not_active Expired - Lifetime
- 2001-02-12 MX MXPA02007819A patent/MXPA02007819A/es active IP Right Grant
- 2001-02-12 US US10/203,890 patent/US6841554B2/en not_active Expired - Lifetime
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- 2001-02-12 SK SK1174-2002A patent/SK287144B6/sk not_active IP Right Cessation
- 2001-02-12 DK DK01904167T patent/DK1263739T3/da active
- 2001-02-12 EE EEP200200445A patent/EE05288B1/xx not_active IP Right Cessation
- 2001-02-12 JP JP2001560189A patent/JP4099333B2/ja not_active Expired - Lifetime
- 2001-02-12 KR KR1020027010581A patent/KR100708262B1/ko not_active IP Right Cessation
- 2001-02-12 EP EP07118593A patent/EP1873148B1/en not_active Expired - Lifetime
- 2001-02-12 BR BR0108378-3A patent/BR0108378A/pt not_active Application Discontinuation
- 2001-02-12 AU AU32084/01A patent/AU775569B2/en not_active Ceased
- 2001-02-12 SI SI200130956T patent/SI1873148T1/sl unknown
- 2001-02-12 CZ CZ20022754A patent/CZ302136B6/cs not_active IP Right Cessation
- 2001-02-12 PT PT01904167T patent/PT1263739E/pt unknown
- 2001-02-12 EP EP01904167A patent/EP1263739B9/en not_active Expired - Lifetime
- 2001-02-12 AT AT07118593T patent/ATE449079T1/de active
- 2001-02-12 DE DE60140581T patent/DE60140581D1/de not_active Expired - Lifetime
- 2001-02-12 CA CA002397450A patent/CA2397450C/en not_active Expired - Fee Related
- 2001-02-12 SI SI200130805T patent/SI1263739T1/sl unknown
- 2001-02-12 AT AT01904167T patent/ATE382610T1/de active
- 2001-02-12 HU HU0204051A patent/HU228422B1/hu not_active IP Right Cessation
- 2001-02-12 CN CNB018050271A patent/CN1210266C/zh not_active Expired - Lifetime
- 2001-02-12 DE DE60132178T patent/DE60132178T2/de not_active Expired - Lifetime
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- 2001-02-12 RU RU2002124621/04A patent/RU2265599C2/ru not_active IP Right Cessation
- 2001-02-12 ES ES07118593T patent/ES2335542T3/es not_active Expired - Lifetime
- 2001-02-12 PT PT07118593T patent/PT1873148E/pt unknown
- 2001-02-12 IL IL15080701A patent/IL150807A0/xx active IP Right Grant
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- 2001-02-13 MY MYPI20010646A patent/MY129018A/en unknown
- 2001-02-14 CO CO01011529A patent/CO5280213A1/es not_active Application Discontinuation
- 2001-02-15 AR ARP010100696A patent/AR029228A1/es unknown
- 2001-06-23 SA SA01220166A patent/SA01220166B1/ar unknown
- 2001-12-02 UA UA2002097448A patent/UA74567C2/uk unknown
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2002
- 2002-07-03 ZA ZA200205331A patent/ZA200205331B/xx unknown
- 2002-07-18 IL IL150807A patent/IL150807A/en not_active IP Right Cessation
- 2002-07-31 BG BG106969A patent/BG65562B1/bg unknown
- 2002-08-09 IS IS6494A patent/IS2592B/is unknown
- 2002-08-14 NO NO20023853A patent/NO323770B1/no not_active IP Right Cessation
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2003
- 2003-05-26 HK HK03103705A patent/HK1051532A1/xx not_active IP Right Cessation
- 2003-11-12 HK HK03108229A patent/HK1055958A1/xx not_active IP Right Cessation
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2004
- 2004-11-10 US US10/985,019 patent/US7129352B2/en not_active Expired - Lifetime
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2008
- 2008-03-03 CY CY20081100245T patent/CY1107225T1/el unknown
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2010
- 2010-01-25 CY CY20101100075T patent/CY1109756T1/el unknown
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