JP2002510197A - ＨＭＧ−ＣｏＡリダクターゼ阻害剤の調製法 - Google Patents
ＨＭＧ−ＣｏＡリダクターゼ阻害剤の調製法Info
- Publication number
- JP2002510197A JP2002510197A JP54772598A JP54772598A JP2002510197A JP 2002510197 A JP2002510197 A JP 2002510197A JP 54772598 A JP54772598 A JP 54772598A JP 54772598 A JP54772598 A JP 54772598A JP 2002510197 A JP2002510197 A JP 2002510197A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- composition
- toluene
- carbon atoms
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims abstract description 69
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 title description 5
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 209
- 150000001875 compounds Chemical class 0.000 claims abstract description 95
- 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 claims abstract description 45
- 229920005989 resin Polymers 0.000 claims abstract description 45
- 239000011347 resin Substances 0.000 claims abstract description 45
- 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 claims abstract description 32
- 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 claims abstract description 32
- 229960004844 lovastatin Drugs 0.000 claims abstract description 32
- 239000000706 filtrate Substances 0.000 claims abstract description 28
- VGMFHMLQOYWYHN-UHFFFAOYSA-N Compactin Natural products OCC1OC(OC2C(O)C(O)C(CO)OC2Oc3cc(O)c4C(=O)C(=COc4c3)c5ccc(O)c(O)c5)C(O)C(O)C1O VGMFHMLQOYWYHN-UHFFFAOYSA-N 0.000 claims abstract description 5
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 claims abstract description 5
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims abstract description 5
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims abstract description 5
- 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 claims abstract description 4
- 238000002425 crystallisation Methods 0.000 claims abstract description 4
- 230000008025 crystallization Effects 0.000 claims abstract description 4
- 229960002965 pravastatin Drugs 0.000 claims abstract description 4
- 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 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 81
- 239000002904 solvent Substances 0.000 claims description 46
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 44
- 125000004432 carbon atom Chemical group C* 0.000 claims description 36
- 239000003125 aqueous solvent Substances 0.000 claims description 22
- 238000010438 heat treatment Methods 0.000 claims description 15
- 238000007273 lactonization reaction Methods 0.000 claims description 11
- 230000002209 hydrophobic effect Effects 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 238000010828 elution Methods 0.000 claims description 4
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- 229920005990 polystyrene resin Polymers 0.000 claims description 2
- 239000006228 supernatant Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 30
- 238000000855 fermentation Methods 0.000 abstract description 15
- 230000004151 fermentation Effects 0.000 abstract description 15
- 239000002243 precursor Substances 0.000 abstract description 13
- 239000003112 inhibitor Substances 0.000 abstract description 9
- 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 abstract description 8
- 238000001914 filtration Methods 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000002028 Biomass Substances 0.000 abstract description 4
- 230000002378 acidificating effect Effects 0.000 abstract description 3
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 230000000274 adsorptive effect Effects 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- 239000012071 phase Substances 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 14
- QLJODMDSTUBWDW-BXMDZJJMSA-N mevinolinic acid 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](C)C=C21 QLJODMDSTUBWDW-BXMDZJJMSA-N 0.000 description 13
- 244000005700 microbiome Species 0.000 description 13
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- 238000000605 extraction Methods 0.000 description 10
- 239000007788 liquid Substances 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 239000013078 crystal Substances 0.000 description 8
- 238000002955 isolation Methods 0.000 description 8
- 239000006227 byproduct Substances 0.000 description 7
- 239000003513 alkali Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 5
- 241001465318 Aspergillus terreus Species 0.000 description 4
- 229940123934 Reductase inhibitor Drugs 0.000 description 4
- 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 4
- 238000001816 cooling Methods 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 241000233866 Fungi Species 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000004316 Oxidoreductases Human genes 0.000 description 3
- 108090000854 Oxidoreductases Proteins 0.000 description 3
- 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 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 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 3
- 229960002855 simvastatin Drugs 0.000 description 3
- 238000001179 sorption measurement Methods 0.000 description 3
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical class OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 2
- -1 1-3N Chemical compound 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- 241000228143 Penicillium Species 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 150000002596 lactones Chemical class 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 238000004659 sterilization and disinfection Methods 0.000 description 2
- 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 description 2
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 241000228212 Aspergillus Species 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
- 241000283074 Equus asinus Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- 241000221929 Hypomyces Species 0.000 description 1
- 241000228347 Monascus <ascomycete fungus> Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241001236817 Paecilomyces <Clavicipitaceae> Species 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 241001503951 Phoma Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000222350 Pleurotus Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 241000223259 Trichoderma Species 0.000 description 1
- IFIFFBWHLKGTMO-SJIDJMGWSA-N [(1s,3s,4ar,7s,8s,8as)-8-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[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 IFIFFBWHLKGTMO-SJIDJMGWSA-N 0.000 description 1
- GZGUDHDMNATZDU-CRMSOXFQSA-N [(4r)-2-[2-[(1s,2s,6r,8s,8ar)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]ethyl]-6-oxooxan-4-yl] (3r,5r)-7-[(1s,2s,6r,8s,8ar)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydrox Chemical compound C([C@@H]1C)=CC2=C[C@H](C)C[C@H](OC(=O)[C@@H](C)CC)[C@@H]2[C@H]1CCC(OC(=O)C1)C[C@H]1OC(=O)C[C@H](O)C[C@H](O)CC[C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@H](OC(=O)[C@@H](C)CC)[C@H]12 GZGUDHDMNATZDU-CRMSOXFQSA-N 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000006103 coloring component Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 239000007854 depigmenting agent Substances 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 238000005805 hydroxylation reaction Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000002336 sorption--desorption measurement Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 235000013619 trace mineral Nutrition 0.000 description 1
- 239000011573 trace mineral Substances 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/62—Carboxylic acid esters
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/56—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/58—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/30—Oxygen atoms, e.g. delta-lactones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Genetics & Genomics (AREA)
- Animal Behavior & Ethology (AREA)
- General Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrane Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP97303111.5 | 1997-05-07 | ||
| EP97303111A EP0877089A1 (en) | 1997-05-07 | 1997-05-07 | HMG-CoA reductase inhibitor preparation process |
| PCT/EP1998/002616 WO1998050572A1 (en) | 1997-05-07 | 1998-05-04 | HMG-CoA REDUCTASE INHIBITOR PREPARATION PROCESS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002510197A true JP2002510197A (ja) | 2002-04-02 |
| JP2002510197A5 JP2002510197A5 (https=) | 2005-01-13 |
Family
ID=8229319
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP54772598A Ceased JP2002510197A (ja) | 1997-05-07 | 1998-05-04 | ＨＭＧ−ＣｏＡリダクターゼ阻害剤の調製法 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US6268186B1 (https=) |
| EP (2) | EP0877089A1 (https=) |
| JP (1) | JP2002510197A (https=) |
| AU (1) | AU7761398A (https=) |
| HU (1) | HUP0002103A3 (https=) |
| IL (1) | IL132786A0 (https=) |
| WO (1) | WO1998050572A1 (https=) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3422791B2 (ja) | 2002-08-06 | 2003-06-30 | 三共株式会社 | プラバスタチンの単離・精製方法 |
| JP3463881B2 (ja) | 2002-08-06 | 2003-11-05 | 三共株式会社 | プラバスタチン又はその薬理上許容される塩の単離・精製方法 |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0251582A (ja) * | 1988-08-12 | 1990-02-21 | Kyokado Eng Co Ltd | 地盤注入用薬液 |
| US7141602B2 (en) * | 1998-09-18 | 2006-11-28 | Lek Pharmaceuticals D.D. | Process for obtaining HMG-CoA reductase inhibitors of high purity |
| SI20072A (sl) * | 1998-09-18 | 2000-04-30 | LEK, tovarna farmacevtskih in kemi�nih izdelkov, d.d. | Postopek za pridobivanje inhibitorjev HMG-CoA reduktaze |
| US6372462B2 (en) | 1999-10-15 | 2002-04-16 | Medmyco Ltd. | Process for producing, methods and compositions of cholesterol lowering agents from higher basidiomycetes mushrooms |
| CN1468098A (zh) * | 2000-10-05 | 2004-01-14 | �ݰ¸Ƕ�ҩ������˾ | 基本上无普伐他汀内酯和表普伐他汀的普伐他汀钠和包含普伐他汀钠的组合物 |
| KR100379075B1 (en) * | 2002-03-07 | 2003-04-08 | Jinis Biopharmaceuticals Co | Method for producing low cholesterol animal food product and food product therefrom |
| US20050003499A1 (en) * | 2003-06-09 | 2005-01-06 | Vilmos Keri | Ion-exchange filtration of fermentation broth |
| ES2239533B1 (es) * | 2004-03-01 | 2006-12-16 | Ercros Industrial, S.A. | Procedimiento para la obtencion de compactina. |
| BRPI0418644A (pt) * | 2004-03-30 | 2007-05-29 | Lupin Ltd | processo para a preparação de um composto |
| US8080560B2 (en) | 2004-12-17 | 2011-12-20 | 3M Innovative Properties Company | Immune response modifier formulations containing oleic acid and methods |
| US8889154B2 (en) | 2005-09-15 | 2014-11-18 | Medicis Pharmaceutical Corporation | Packaging for 1-(2-methylpropyl)-1H-imidazo[4,5-c] quinolin-4-amine-containing formulation |
| CA2659733A1 (en) | 2006-07-31 | 2008-02-07 | 3M Innovative Properties Company | Sterilized topical compositions of 1-(2-methylpropyl)-1h-imidazo[4,5-c]quinolin-4-amine |
| EP2274267B1 (en) * | 2008-04-02 | 2012-01-04 | DSM IP Assets B.V. | Pravastatin extraction |
| RU2585234C2 (ru) * | 2013-12-27 | 2016-05-27 | Открытое акционерное общество "Красфарма" | Способ получения компактина |
| RU2585233C2 (ru) * | 2013-12-27 | 2016-05-27 | Открытое акционерное общество "Красфарма" | Промышленный способ получения компактина |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4294926A (en) * | 1979-06-15 | 1981-10-13 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| US4231938A (en) | 1979-06-15 | 1980-11-04 | Merck & Co., Inc. | Hypocholesteremic fermentation products and process of preparation |
| DK149080C (da) | 1980-06-06 | 1986-07-28 | Sankyo Co | Fremgangsmaade til fremstilling af derivater af ml-236b-carboxylsyre |
| US4940727A (en) * | 1986-06-23 | 1990-07-10 | Merck & Co., Inc. | Novel HMG-CoA reductase inhibitors |
| HU208997B (en) * | 1992-06-17 | 1994-02-28 | Gyogyszerkutato Intezet | Microbiological method for producing mevinoline |
| SI9300303A (en) * | 1993-06-08 | 1994-12-31 | Krka Tovarna Zdravil | Process for isolation of hypolipemic effective substance |
| US5989877A (en) * | 1995-08-03 | 1999-11-23 | Gist-Brocades B.V. | Selective process for the deacylation of acylated compounds |
| WO1997006128A1 (en) * | 1995-08-03 | 1997-02-20 | Gist-Brocades B.V. | Selective process for the deacylation of acylated compounds |
-
1997
- 1997-05-07 EP EP97303111A patent/EP0877089A1/en not_active Withdrawn
-
1998
- 1998-05-04 WO PCT/EP1998/002616 patent/WO1998050572A1/en not_active Ceased
- 1998-05-04 JP JP54772598A patent/JP2002510197A/ja not_active Ceased
- 1998-05-04 US US09/423,370 patent/US6268186B1/en not_active Expired - Fee Related
- 1998-05-04 EP EP98925525A patent/EP0980437A1/en not_active Withdrawn
- 1998-05-04 HU HU0002103A patent/HUP0002103A3/hu unknown
- 1998-05-04 IL IL13278698A patent/IL132786A0/xx unknown
- 1998-05-04 AU AU77613/98A patent/AU7761398A/en not_active Abandoned
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3422791B2 (ja) | 2002-08-06 | 2003-06-30 | 三共株式会社 | プラバスタチンの単離・精製方法 |
| JP3463881B2 (ja) | 2002-08-06 | 2003-11-05 | 三共株式会社 | プラバスタチン又はその薬理上許容される塩の単離・精製方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0002103A1 (hu) | 2000-10-28 |
| HUP0002103A3 (en) | 2001-10-29 |
| US6268186B1 (en) | 2001-07-31 |
| AU7761398A (en) | 1998-11-27 |
| EP0877089A1 (en) | 1998-11-11 |
| EP0980437A1 (en) | 2000-02-23 |
| WO1998050572A1 (en) | 1998-11-12 |
| IL132786A0 (en) | 2001-03-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2002510197A (ja) | ＨＭＧ−ＣｏＡリダクターゼ阻害剤の調製法 | |
| EP0702679B1 (en) | Process for the isolation of lovastatin | |
| WO1994029292A9 (en) | Process for the isolation of lovastatin | |
| RU2265665C2 (ru) | Способ очистки ферментационного бульона | |
| JP2002526467A (ja) | 新規のＨＭＧ−ＣｏＡレダクターゼインヒビターの塩 | |
| JP2005110693A (ja) | ＨＭＧ−ＣｏＡリダクターゼ阻害剤の精製方法、ＨＭＧ−ＣｏＡリダクターゼ阻害剤、および上記方法の使用 | |
| CA2243592C (en) | Method of production of lovastatin | |
| CA2412566A1 (en) | Process for the isolation of lovastatin | |
| RU2166506C2 (ru) | Способ получения и/или очистки клавулановой кислоты или ее фармацевтически приемлемой соли или эфира и способ ее отделения от содержащейся в отфильтрованном ферментационном бульоне примеси клавам-2-карбоновой кислоты | |
| EP0813536A1 (en) | Process for the preparation of pharmaceutically acceptable salts of clavulanic acid | |
| JPH11501218A (ja) | アシル化された化合物の脱アシル化の選択的方法 | |
| US7696363B2 (en) | Preparation of flavonoid compounds | |
| EP0937084A1 (en) | Process for the preparation of salts and esters of clavulanic acid | |
| EP1673361B1 (en) | A method for the manufacture of lovastatin | |
| JP4770032B2 (ja) | シアタン誘導体 | |
| WO1995011295A1 (en) | An improved process to recover an aqueous fermentation broth | |
| RU2522806C1 (ru) | Усовершенствованный способ очистки правастатина | |
| WO2004111255A1 (en) | Ion-exchange filtration of fermentation broth | |
| AU692091C (en) | Preparation of clavulanate salts | |
| WO1998042858A1 (en) | Process for the isolation of a pharmaceutically acceptable alkali metal salt of clavulanic acid | |
| JPS61247398A (ja) | サリノマイシン類の製法 | |
| JP2000236894A (ja) | ラディシコールの製造方法 | |
| SK3392001A3 (sk) | Spôsob izolácie vermikulínu | |
| JPH0625180B2 (ja) | 新規マクロサイクリック・ラクタム・ラクトン系物質及びその製造方法 | |
| BG60744B1 (bg) | метод за изолиране и пречистване на ловастатин |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040406 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040406 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20050111 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 19921220 |
|
| A313 | Final decision of rejection without a dissenting response from the applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A313 Effective date: 20050530 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20050705 |