IL142055A - SALTS OF HMG-CoA REDUCTASE INHIBITORS AND THEIR PREPARATION - Google Patents

SALTS OF HMG-CoA REDUCTASE INHIBITORS AND THEIR PREPARATION

Info

Publication number: IL142055A
Authority: IL; Israel
Prior art keywords: alkyl; group; hmg; substituted; coa reductase
Prior art date: 1998-09-18

Application number

IL14205599A

Other languages

English (en)

Other versions

IL142055A0 (en

Inventor

Zlatko Pflaum

Original Assignee

Lek Tovarna Farmacevtskih

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.)

1998-09-18

Filing date

1999-09-17

Publication date

2004-06-20

1999-09-17 Application filed by Lek Tovarna Farmacevtskih filed Critical Lek Tovarna Farmacevtskih

2002-03-10 Publication of IL142055A0 publication Critical patent/IL142055A0/xx

2004-06-20 Publication of IL142055A publication Critical patent/IL142055A/en

Links

229940121710 HMGCoA reductase inhibitor Drugs 0.000 title claims abstract description 104
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title claims abstract description 103
238000002360 preparation method Methods 0.000 title claims description 43
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title description 52
125000000217 alkyl group Chemical group 0.000 claims abstract description 55
150000001412 amines Chemical class 0.000 claims abstract description 54
150000003839 salts Chemical class 0.000 claims abstract description 54
-1 octahydronaphthalene oxime derivative of ML-236A Chemical class 0.000 claims abstract description 41
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 40
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 35
239000001257 hydrogen Substances 0.000 claims abstract description 35
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 35
125000003342 alkenyl group Chemical group 0.000 claims abstract description 30
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 25
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 24
125000003277 amino group Chemical group 0.000 claims abstract description 24
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 24
229960004844 lovastatin Drugs 0.000 claims abstract description 24
PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical group 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 24
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 24
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims abstract description 20
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims abstract description 19
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims abstract description 19
125000001424 substituent group Chemical group 0.000 claims abstract description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 10
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 10
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 10
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims abstract description 9
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims abstract description 9
NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 claims abstract description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 7
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 claims abstract description 6
SVYKKECYCPFKGB-UHFFFAOYSA-N N,N-dimethylcyclohexylamine Chemical compound CN(C)C1CCCCC1 SVYKKECYCPFKGB-UHFFFAOYSA-N 0.000 claims abstract description 6
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims abstract description 6
125000003118 aryl group Chemical group 0.000 claims abstract description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 claims abstract description 6
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
229910052736 halogen Inorganic materials 0.000 claims abstract description 6
150000002367 halogens Chemical class 0.000 claims abstract description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
239000001301 oxygen Substances 0.000 claims abstract description 6
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims abstract description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 5
125000004122 cyclic group Chemical group 0.000 claims abstract description 5
VXVVUHQULXCUPF-UHFFFAOYSA-N cycloheptanamine Chemical compound NC1CCCCCC1 VXVVUHQULXCUPF-UHFFFAOYSA-N 0.000 claims abstract description 5
125000005842 heteroatom Chemical group 0.000 claims abstract description 5
125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 5
125000000879 imine group Chemical group 0.000 claims abstract description 5
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
125000003107 substituted aryl group Chemical group 0.000 claims abstract description 5
125000005750 substituted cyclic group Chemical group 0.000 claims abstract description 5
QIJIUJYANDSEKG-UHFFFAOYSA-N 2,4,4-trimethylpentan-2-amine Chemical compound CC(C)(C)CC(C)(C)N QIJIUJYANDSEKG-UHFFFAOYSA-N 0.000 claims abstract description 4
AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 claims abstract description 3
RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 claims abstract description 3
LTHNHFOGQMKPOV-UHFFFAOYSA-N 2-ethylhexan-1-amine Chemical compound CCCCC(CC)CN LTHNHFOGQMKPOV-UHFFFAOYSA-N 0.000 claims abstract description 3
WGTASENVNYJZBK-UHFFFAOYSA-N 3,4,5-trimethoxyamphetamine Chemical compound COC1=CC(CC(C)N)=CC(OC)=C1OC WGTASENVNYJZBK-UHFFFAOYSA-N 0.000 claims abstract description 3
AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 claims abstract description 3
XXBDWLFCJWSEKW-UHFFFAOYSA-N dimethylbenzylamine Chemical compound CN(C)CC1=CC=CC=C1 XXBDWLFCJWSEKW-UHFFFAOYSA-N 0.000 claims abstract description 3
MXHTZQSKTCCMFG-UHFFFAOYSA-N n,n-dibenzyl-1-phenylmethanamine Chemical compound C=1C=CC=CC=1CN(CC=1C=CC=CC=1)CC1=CC=CC=C1 MXHTZQSKTCCMFG-UHFFFAOYSA-N 0.000 claims abstract description 3
ABRGFZIXRKAUJS-UHFFFAOYSA-N n-benzyl-n-methylethanamine Chemical compound CCN(C)CC1=CC=CC=C1 ABRGFZIXRKAUJS-UHFFFAOYSA-N 0.000 claims abstract description 3
VFPQRGMSTSEZFW-UHFFFAOYSA-N n-ethylcycloheptanamine Chemical compound CCNC1CCCCCC1 VFPQRGMSTSEZFW-UHFFFAOYSA-N 0.000 claims abstract description 3
AGVKXDPPPSLISR-UHFFFAOYSA-N n-ethylcyclohexanamine Chemical compound CCNC1CCCCC1 AGVKXDPPPSLISR-UHFFFAOYSA-N 0.000 claims abstract description 3
RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 claims abstract description 3
KKTBUCVHSCATGB-UHFFFAOYSA-N n-methylcyclopentanamine Chemical compound CNC1CCCC1 KKTBUCVHSCATGB-UHFFFAOYSA-N 0.000 claims abstract description 3
IOQPZZOEVPZRBK-UHFFFAOYSA-N octan-1-amine Chemical compound CCCCCCCCN IOQPZZOEVPZRBK-UHFFFAOYSA-N 0.000 claims abstract description 3
LXZBFUBRYYVRQJ-AXHZAXLDSA-M sodium;(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-dihydroxyheptanoate Chemical compound [Na+].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 LXZBFUBRYYVRQJ-AXHZAXLDSA-M 0.000 claims abstract description 3
229940123934 Reductase inhibitor Drugs 0.000 claims abstract 3
238000000034 method Methods 0.000 claims description 76
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 36
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 description 35
229960002965 pravastatin Drugs 0.000 claims description 35
239000013078 crystal Substances 0.000 claims description 33
239000000126 substance Substances 0.000 claims description 32
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 claims description 25
229960002855 simvastatin Drugs 0.000 claims description 25
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 24
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 description 24
238000000855 fermentation Methods 0.000 claims description 24
230000004151 fermentation Effects 0.000 claims description 24
229950009116 mevastatin Drugs 0.000 claims description 24
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 claims description 24
239000002253 acid Substances 0.000 claims description 23
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 description 23
238000002425 crystallisation Methods 0.000 claims description 19
150000002596 lactones Chemical group 0.000 claims description 18
159000000000 sodium salts Chemical group 0.000 claims description 17
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 claims description 16
JQVDAXLFBXTEQA-UHFFFAOYSA-N dibutylamine Chemical compound CCCCNCCCC JQVDAXLFBXTEQA-UHFFFAOYSA-N 0.000 claims description 16
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 claims description 15
229960005370 atorvastatin Drugs 0.000 claims description 15
238000002955 isolation Methods 0.000 claims description 13
XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 claims description 12
BHRZNVHARXXAHW-UHFFFAOYSA-N sec-butylamine Chemical compound CCC(C)N BHRZNVHARXXAHW-UHFFFAOYSA-N 0.000 claims description 11
238000004519 manufacturing process Methods 0.000 claims description 10
239000003960 organic solvent Substances 0.000 claims description 10
238000000746 purification Methods 0.000 claims description 10
GELMWIVBBPAMIO-UHFFFAOYSA-N 2-methylbutan-2-amine Chemical compound CCC(C)(C)N GELMWIVBBPAMIO-UHFFFAOYSA-N 0.000 claims description 9
238000012986 modification Methods 0.000 claims description 9
230000004048 modification Effects 0.000 claims description 9
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 description 9
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 claims description 8
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 8
229960003765 fluvastatin Drugs 0.000 claims description 8
239000003112 inhibitor Substances 0.000 claims description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 5
159000000007 calcium salts Chemical class 0.000 claims description 5
229910052751 metal Inorganic materials 0.000 claims description 5
239000002184 metal Substances 0.000 claims description 5
244000005700 microbiome Species 0.000 claims description 5
239000011541 reaction mixture Substances 0.000 claims description 5
XDIAMRVROCPPBK-UHFFFAOYSA-N 2,2-dimethylpropan-1-amine Chemical compound CC(C)(C)CN XDIAMRVROCPPBK-UHFFFAOYSA-N 0.000 claims description 4
DXSUORGKJZADET-UHFFFAOYSA-N 3,3-dimethylbutan-2-amine Chemical compound CC(N)C(C)(C)C DXSUORGKJZADET-UHFFFAOYSA-N 0.000 claims description 4
DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 4
229960003805 amantadine Drugs 0.000 claims description 4
KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 claims description 4
DTSDBGVDESRKKD-UHFFFAOYSA-N n'-(2-aminoethyl)propane-1,3-diamine Chemical compound NCCCNCCN DTSDBGVDESRKKD-UHFFFAOYSA-N 0.000 claims description 4
KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 claims description 4
MFIGJRRHGZYPDD-UHFFFAOYSA-N n,n'-di(propan-2-yl)ethane-1,2-diamine Chemical compound CC(C)NCCNC(C)C MFIGJRRHGZYPDD-UHFFFAOYSA-N 0.000 claims description 4
UYYCVBASZNFFRX-UHFFFAOYSA-N n-propan-2-ylcyclohexanamine Chemical compound CC(C)NC1CCCCC1 UYYCVBASZNFFRX-UHFFFAOYSA-N 0.000 claims description 4
102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 claims description 3
108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims description 3
239000006057 Non-nutritive feed additive Substances 0.000 claims description 3
239000005700 Putrescine Substances 0.000 claims description 3
238000007385 chemical modification Methods 0.000 claims description 3
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
238000011138 biotechnological process Methods 0.000 claims description 2
XRCAFTMYEHRXQO-UHFFFAOYSA-N cycloheptanamine;cyclohexanamine Chemical compound NC1CCCCC1.NC1CCCCCC1 XRCAFTMYEHRXQO-UHFFFAOYSA-N 0.000 claims description 2
238000001035 drying Methods 0.000 claims description 2
230000002255 enzymatic effect Effects 0.000 claims description 2
238000001914 filtration Methods 0.000 claims description 2
QHJABUZHRJTCAR-UHFFFAOYSA-N n'-methylpropane-1,3-diamine Chemical compound CNCCCN QHJABUZHRJTCAR-UHFFFAOYSA-N 0.000 claims description 2
238000006257 total synthesis reaction Methods 0.000 claims description 2
238000005406 washing Methods 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 15
MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical class CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 claims 1
KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 claims 1
TXXWBTOATXBWDR-UHFFFAOYSA-N n,n,n',n'-tetramethylhexane-1,6-diamine Chemical compound CN(C)CCCCCCN(C)C TXXWBTOATXBWDR-UHFFFAOYSA-N 0.000 claims 1
DPBLXKKOBLCELK-UHFFFAOYSA-N pentan-1-amine Chemical group CCCCCN DPBLXKKOBLCELK-UHFFFAOYSA-N 0.000 claims 1
ZEPRYRDSABELMO-UHFFFAOYSA-N n,n-diethylcycloheptanamine Chemical compound CCN(CC)C1CCCCCC1 ZEPRYRDSABELMO-UHFFFAOYSA-N 0.000 abstract description 2
ZEFLPHRHPMEVPM-UHFFFAOYSA-N n,n-dimethylcyclopentanamine Chemical compound CN(C)C1CCCC1 ZEFLPHRHPMEVPM-UHFFFAOYSA-N 0.000 abstract 1
ZWRDBWDXRLPESY-UHFFFAOYSA-N n-benzyl-n-ethylethanamine Chemical compound CCN(CC)CC1=CC=CC=C1 ZWRDBWDXRLPESY-UHFFFAOYSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
239000000243 solution Substances 0.000 description 29
TUZYXOIXSAXUGO-PZAWKZKUSA-M pravastatin(1-) 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-M 0.000 description 28
238000006243 chemical reaction Methods 0.000 description 18
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 12
238000004128 high performance liquid chromatography Methods 0.000 description 12
239000000047 product Substances 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
239000000203 mixture Substances 0.000 description 9
239000000543 intermediate Substances 0.000 description 8
239000012071 phase Substances 0.000 description 8
239000007864 aqueous solution Substances 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
229910000147 aluminium phosphate Inorganic materials 0.000 description 6
239000002024 ethyl acetate extract Substances 0.000 description 6
229920001817 Agar Polymers 0.000 description 5
239000008272 agar Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
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 4
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 4
239000002274 desiccant Substances 0.000 description 4
239000008103 glucose Substances 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000002994 raw material Substances 0.000 description 4
JOZZAIIGWFLONA-UHFFFAOYSA-N 3-methylbutan-2-amine Chemical compound CC(C)C(C)N JOZZAIIGWFLONA-UHFFFAOYSA-N 0.000 description 3
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000000284 extract Substances 0.000 description 3
238000000605 extraction Methods 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
244000068988 Glycine max Species 0.000 description 2
235000010469 Glycine max Nutrition 0.000 description 2
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AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
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235000001014 amino acid Nutrition 0.000 description 2
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
125000000962 organic group Chemical group 0.000 description 2
229960003104 ornithine Drugs 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000002243 precursor Substances 0.000 description 2
RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 2
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OJRHUICOVVSGSY-RXMQYKEDSA-N (2s)-2-chloro-3-methylbutan-1-ol Chemical class CC(C)[C@H](Cl)CO OJRHUICOVVSGSY-RXMQYKEDSA-N 0.000 description 1
CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical class 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 1
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
241000187643 Amycolatopsis Species 0.000 description 1
241000228212 Aspergillus Species 0.000 description 1
241001465318 Aspergillus terreus Species 0.000 description 1
239000002028 Biomass Substances 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
229930064664 L-arginine Natural products 0.000 description 1
235000014852 L-arginine Nutrition 0.000 description 1
241000228347 Monascus <ascomycete fungus> Species 0.000 description 1
241000235395 Mucor Species 0.000 description 1
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Natural products CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
241000187654 Nocardia Species 0.000 description 1
241000228143 Penicillium Species 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
125000003545 alkoxy group Chemical group 0.000 description 1
235000012538 ammonium bicarbonate Nutrition 0.000 description 1
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238000004458 analytical method Methods 0.000 description 1
229910052925 anhydrite Inorganic materials 0.000 description 1
239000002518 antifoaming agent Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
MSWZFWKMSRAUBD-QZABAPFNSA-N beta-D-glucosamine Chemical class N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-QZABAPFNSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 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
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
150000007942 carboxylates Chemical group 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
WWSNTLOVYSRDEL-DZSDEGEFSA-N compactin diol lactone Chemical compound C([C@@H]1[C@H]2[C@@H](O)CCC=C2C=C[C@@H]1C)C[C@@H]1C[C@@H](O)CC(=O)O1 WWSNTLOVYSRDEL-DZSDEGEFSA-N 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
WWSNTLOVYSRDEL-UHFFFAOYSA-N desmethylmonacolin J Natural products CC1C=CC2=CCCC(O)C2C1CCC1CC(O)CC(=O)O1 WWSNTLOVYSRDEL-UHFFFAOYSA-N 0.000 description 1
150000004985 diamines Chemical class 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
238000011031 large-scale manufacturing process Methods 0.000 description 1
239000007788 liquid Substances 0.000 description 1
231100000053 low toxicity Toxicity 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
230000002906 microbiologic effect Effects 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
238000010979 pH adjustment Methods 0.000 description 1
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
238000004904 shortening Methods 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C211/09—Diamines
- C07C211/10—Diaminoethanes
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C211/03—Monoamines
- C07C211/07—Monoamines containing one, two or three alkyl groups, each having the same number of carbon atoms in excess of three
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C211/09—Diamines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
- C07C211/02—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C211/14—Amines containing amino groups bound to at least two aminoalkyl groups, e.g. diethylenetriamines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
- C07C211/33—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C211/34—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton
- C07C211/35—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of rings other than six-membered aromatic rings of a saturated carbon skeleton containing only non-condensed rings
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrane Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Plural Heterocyclic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Pyrrole Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

IL14205599A 1998-09-18 1999-09-17 SALTS OF HMG-CoA REDUCTASE INHIBITORS AND THEIR PREPARATION IL142055A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SI9800240A SI20070A (sl)	1998-09-18	1998-09-18	Nove soli inhibitorjev HMG-CoA reduktaze
PCT/IB1999/001554 WO2000017150A1 (fr)	1998-09-18	1999-09-17	NOUVEAUX SELS D'INHIBITEURS DE LA HMG-CoA REDUCTASE

Publications (2)

Publication Number	Publication Date
IL142055A0 IL142055A0 (en)	2002-03-10
IL142055A true IL142055A (en)	2004-06-20

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US (4)	US6583295B1 (fr)
EP (2)	EP1114021B1 (fr)
JP (1)	JP3834203B2 (fr)
KR (1)	KR100699368B1 (fr)
CN (1)	CN1228304C (fr)
AT (1)	ATE271026T1 (fr)
AU (1)	AU765373C (fr)
CA (1)	CA2343646A1 (fr)
DE (1)	DE69918697T2 (fr)
HU (1)	HUP0103007A3 (fr)
IL (1)	IL142055A (fr)
IS (1)	IS2113B (fr)
NZ (1)	NZ509583A (fr)
SI (1)	SI20070A (fr)
WO (1)	WO2000017150A1 (fr)

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1998
- 1998-09-18 SI SI9800240A patent/SI20070A/sl not_active IP Right Cessation
1999
- 1999-09-17 JP JP2000574060A patent/JP3834203B2/ja not_active Expired - Lifetime
- 1999-09-17 CN CNB998110736A patent/CN1228304C/zh not_active Expired - Lifetime
- 1999-09-17 EP EP99941798A patent/EP1114021B1/fr not_active Expired - Lifetime
- 1999-09-17 WO PCT/IB1999/001554 patent/WO2000017150A1/fr not_active Ceased
- 1999-09-17 EP EP04011699A patent/EP1466886A3/fr not_active Withdrawn
- 1999-09-17 KR KR1020017000758A patent/KR100699368B1/ko not_active Expired - Fee Related
- 1999-09-17 AT AT99941798T patent/ATE271026T1/de active
- 1999-09-17 DE DE69918697T patent/DE69918697T2/de not_active Expired - Lifetime
- 1999-09-17 HU HU0103007A patent/HUP0103007A3/hu unknown
- 1999-09-17 IL IL14205599A patent/IL142055A/en not_active IP Right Cessation
- 1999-09-17 US US09/787,387 patent/US6583295B1/en not_active Expired - Lifetime
- 1999-09-17 NZ NZ509583A patent/NZ509583A/en not_active IP Right Cessation
- 1999-09-17 AU AU55285/99A patent/AU765373C/en not_active Expired
- 1999-09-17 CA CA002343646A patent/CA2343646A1/fr not_active Abandoned
2001
- 2001-03-15 IS IS5891A patent/IS2113B/is unknown
2002
- 2002-12-16 US US10/320,285 patent/US6838566B2/en not_active Expired - Lifetime
2004
- 2004-10-15 US US10/966,000 patent/US20050049422A1/en not_active Abandoned
2007
- 2007-09-18 US US11/901,634 patent/US20080188552A1/en not_active Abandoned

Also Published As

Publication number	Publication date
IL142055A0 (en)	2002-03-10
US20030120086A1 (en)	2003-06-26
KR100699368B1 (ko)	2007-03-27
KR20010071959A (ko)	2001-07-31
AU765373C (en)	2005-05-26
IS2113B (is)	2006-06-15
US20080188552A1 (en)	2008-08-07
US6583295B1 (en)	2003-06-24
CA2343646A1 (fr)	2000-03-30
SI20070A (sl)	2000-04-30
EP1466886A2 (fr)	2004-10-13
AU5528599A (en)	2000-04-10
CN1318046A (zh)	2001-10-17
IS5891A (is)	2001-03-15
ATE271026T1 (de)	2004-07-15
JP2002526467A (ja)	2002-08-20
EP1114021A1 (fr)	2001-07-11
NZ509583A (en)	2003-10-31
JP3834203B2 (ja)	2006-10-18
CN1228304C (zh)	2005-11-23
WO2000017150A1 (fr)	2000-03-30
HUP0103007A3 (en)	2003-10-28
EP1114021B1 (fr)	2004-07-14
US20050049422A1 (en)	2005-03-03
DE69918697D1 (de)	2004-08-19
EP1466886A3 (fr)	2009-02-25
DE69918697T2 (de)	2005-07-28
US6838566B2 (en)	2005-01-04
AU765373B2 (en)	2003-09-18
HUP0103007A2 (hu)	2002-05-29

Publication	Publication Date	Title
AU765373C (en)	2005-05-26	New salts of HMG-CoA reductase inhibitors
EP0702679B1 (fr)	1998-04-08	Procede d'isolement de lovastatine
EP0074222B1 (fr)	1985-04-10	Dérivés de MB-530B, leur préparation et compositions pharmaceutiques les contenant
LV11033B (en)	1996-06-20	Process for the lactonization of mevinic acids and analogs thereof
HUP0301423A2 (hu)	2003-08-28	Eljárás lovasztatin izolálására
EP0033537A2 (fr)	1981-08-12	Produits d'hydrogénation de mévinoline et de dihydromévinoline, procédé pour leur préparation et composition pharmaceutique à activité antihypercholestérolémique les contenant
JP2003525935A (ja)	2003-09-02	低下したレベルの二量体不純物を伴うロバスタチン及びシンバスタチンの精製方法
EP0570245B1 (fr)	1996-10-30	Dérivés d'octahydronaphthalène oxime pour l'inhibition de la biosynthèse de cholestérol, leur préparation et utilisation
JP2004520445A5 (fr)	2005-02-17
BG107477A (bg)	2004-01-30	Лактонизационен метод за получаване на симвастатин с висока чистота
MX2007009422A (es)	2007-10-05	Proceso para la elaboracion de simvastatina.

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2020-05-31	EXP	Patent expired