SK579789A3 - Erythro-(e)-3,5-dihydroxy-7-[3'-(4''-fluorophenyl)-1'-(1''- -methylethyl)indol-2'-yl]-hept-6-enoic acid and process for preparing thereof - Google Patents

Erythro-(e)-3,5-dihydroxy-7-[3'-(4''-fluorophenyl)-1'-(1''- -methylethyl)indol-2'-yl]-hept-6-enoic acid and process for preparing thereof Download PDF

Info

Publication number: SK579789A3
Authority: SK; Slovakia
Prior art keywords: formula; compound; ester; compounds; racemic
Prior art date: 1988-10-13

Application number

SK5797-89A

Other languages

English (en)

Slovak (sk)

Other versions

SK280845B6 (sk

Inventor

Kau-Ming Chen

Prasad Koteswara Kapa

George T Lee

Oljan Repic

Petr Hess

Michel Crevoisier

Original Assignee

Novartis Ag

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.)

1988-10-13

Filing date

1989-10-12

Publication date

2000-08-14

Family has litigation

First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26945992&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SK579789(A3) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.

1989-10-12 Application filed by Novartis Ag filed Critical Novartis Ag

2000-08-14 Publication of SK280845B6 publication Critical patent/SK280845B6/sk

2000-08-14 Publication of SK579789A3 publication Critical patent/SK579789A3/sk

Links

FJLGEFLZQAZZCD-JUFISIKESA-N (3S,5R)-fluvastatin Chemical compound 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 FJLGEFLZQAZZCD-JUFISIKESA-N 0.000 title 1
238000004519 manufacturing process Methods 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 137
238000000034 method Methods 0.000 claims abstract description 39
150000002148 esters Chemical class 0.000 claims abstract description 31
-1 triphenylmethyl (trityl) Chemical group 0.000 claims abstract description 24
238000006243 chemical reaction Methods 0.000 claims abstract description 23
239000002253 acid Substances 0.000 claims abstract description 21
150000003839 salts Chemical class 0.000 claims abstract description 19
238000002360 preparation method Methods 0.000 claims abstract description 16
238000011916 stereoselective reduction Methods 0.000 claims abstract description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
125000000422 delta-lactone group Chemical group 0.000 claims abstract description 6
125000004185 ester group Chemical group 0.000 claims abstract description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 4
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 4
239000000203 mixture Substances 0.000 claims description 46
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 34
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 21
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 claims description 14
ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 13
239000012279 sodium borohydride Substances 0.000 claims description 12
229910000033 sodium borohydride Inorganic materials 0.000 claims description 12
125000004122 cyclic group Chemical group 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 8
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
239000012429 reaction media Substances 0.000 claims description 7
239000007858 starting material Substances 0.000 claims description 7
ZDZJOIIBECYKAJ-UHFFFAOYSA-N 3-(4-fluorophenyl)-1-propan-2-ylindole Chemical compound C12=CC=CC=C2N(C(C)C)C=C1C1=CC=C(F)C=C1 ZDZJOIIBECYKAJ-UHFFFAOYSA-N 0.000 claims description 6
150000001450 anions Chemical class 0.000 claims description 6
159000000000 sodium salts Chemical class 0.000 claims description 6
150000001639 boron compounds Chemical class 0.000 claims description 5
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 4
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 claims description 4
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 4
229910052796 boron Inorganic materials 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 3
239000000460 chlorine Substances 0.000 claims description 3
238000002156 mixing Methods 0.000 claims description 3
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
BTOJSYRZQZOMOK-UHFFFAOYSA-N 4-chloro-7-(4-methylphenyl)sulfonylpyrrolo[2,3-d]pyrimidine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=NC(Cl)=C2C=C1 BTOJSYRZQZOMOK-UHFFFAOYSA-N 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
239000012359 Methanesulfonyl chloride Substances 0.000 claims description 2
239000002585 base Substances 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical compound BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 claims description 2
ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 claims description 2
150000002168 ethanoic acid esters Chemical class 0.000 claims description 2
239000012458 free base Substances 0.000 claims description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
NTSFJZORNYYLFW-UHFFFAOYSA-N 4-methylbenzenesulfonyl bromide Chemical compound CC1=CC=C(S(Br)(=O)=O)C=C1 NTSFJZORNYYLFW-UHFFFAOYSA-N 0.000 claims 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
101150065749 Churc1 gene Proteins 0.000 claims 1
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 claims 1
125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 abstract description 11
239000001257 hydrogen Substances 0.000 abstract description 7
229910052739 hydrogen Inorganic materials 0.000 abstract description 7
239000000543 intermediate Substances 0.000 abstract description 4
229910052799 carbon Inorganic materials 0.000 abstract description 3
125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 6
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 abstract 6
125000001153 fluoro group Chemical group F* 0.000 abstract 6
125000004435 hydrogen atom Chemical class [H]* 0.000 abstract 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 6
125000006274 (C1-C3)alkoxy group Chemical group 0.000 abstract 5
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 abstract 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 abstract 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 2
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 abstract 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
230000000879 anti-atherosclerotic effect Effects 0.000 abstract 1
230000001315 anti-hyperlipaemic effect Effects 0.000 abstract 1
239000003529 anticholesteremic agent Substances 0.000 abstract 1
239000003524 antilipemic agent Substances 0.000 abstract 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
125000001246 bromo group Chemical group Br* 0.000 abstract 1
239000003814 drug Substances 0.000 abstract 1
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
229910052760 oxygen Inorganic materials 0.000 abstract 1
239000001301 oxygen Substances 0.000 abstract 1
125000001424 substituent group Chemical group 0.000 abstract 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 abstract 1
239000000243 solution Substances 0.000 description 50
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
239000000047 product Substances 0.000 description 32
239000011541 reaction mixture Substances 0.000 description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
239000002904 solvent Substances 0.000 description 10
238000004821 distillation Methods 0.000 description 9
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
YLMOTKLYENPQLK-VMPITWQZSA-N (e)-3-(n-methylanilino)prop-2-enal Chemical compound O=C/C=C/N(C)C1=CC=CC=C1 YLMOTKLYENPQLK-VMPITWQZSA-N 0.000 description 8
HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 8
239000012074 organic phase Substances 0.000 description 8
239000008367 deionised water Substances 0.000 description 7
229910021641 deionized water Inorganic materials 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
238000010992 reflux Methods 0.000 description 7
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000000126 substance Substances 0.000 description 6
UZKWTJUDCOPSNM-UHFFFAOYSA-N 1-ethenoxybutane Chemical compound CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000012065 filter cake Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 5
239000010410 layer Substances 0.000 description 5
JIKUXBYRTXDNIY-UHFFFAOYSA-N n-methyl-n-phenylformamide Chemical compound O=CN(C)C1=CC=CC=C1 JIKUXBYRTXDNIY-UHFFFAOYSA-N 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
229910000085 borane Inorganic materials 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
238000000354 decomposition reaction Methods 0.000 description 4
239000007789 gas Substances 0.000 description 4
125000000468 ketone group Chemical group 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
238000005406 washing Methods 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
238000009835 boiling Methods 0.000 description 3
FESAXEDIWWXCNG-UHFFFAOYSA-N diethyl(methoxy)borane Chemical compound CCB(CC)OC FESAXEDIWWXCNG-UHFFFAOYSA-N 0.000 description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 3
239000000463 material Substances 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
230000003287 optical effect Effects 0.000 description 3
150000002978 peroxides Chemical class 0.000 description 3
239000012071 phase Substances 0.000 description 3
239000000376 reactant Substances 0.000 description 3
238000006722 reduction reaction Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
229960001922 sodium perborate Drugs 0.000 description 3
YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
ZGEGCLOFRBLKSE-UHFFFAOYSA-N 1-Heptene Chemical compound CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
229930194542 Keto Natural products 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
239000012298 atmosphere Substances 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
239000000284 extract Substances 0.000 description 2
125000001207 fluorophenyl group Chemical group 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
RWNJOXUVHRXHSD-UHFFFAOYSA-N hept-6-enoic acid Chemical compound OC(=O)CCCCC=C RWNJOXUVHRXHSD-UHFFFAOYSA-N 0.000 description 2
230000003301 hydrolyzing effect Effects 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
150000004702 methyl esters Chemical class 0.000 description 2
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
235000010265 sodium sulphite Nutrition 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000011343 solid material Substances 0.000 description 2
230000000707 stereoselective effect Effects 0.000 description 2
JKUYRAMKJLMYLO-UHFFFAOYSA-N tert-butyl 3-oxobutanoate Chemical compound CC(=O)CC(=O)OC(C)(C)C JKUYRAMKJLMYLO-UHFFFAOYSA-N 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
GIZSHQYTTBQKOQ-UHFFFAOYSA-N threo-Syringoylglycerol Chemical compound COC1=CC(C(O)C(O)CO)=CC(OC)=C1O GIZSHQYTTBQKOQ-UHFFFAOYSA-N 0.000 description 2
XLPGQDGLAUEQDH-UHFFFAOYSA-N 3-(n-methylanilino)prop-2-enal;hydrochloride Chemical compound Cl.O=CC=CN(C)C1=CC=CC=C1 XLPGQDGLAUEQDH-UHFFFAOYSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
201000001320 Atherosclerosis Diseases 0.000 description 1
PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 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
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 1
238000005481 NMR spectroscopy Methods 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
JYVXNLLUYHCIIH-ZCFIWIBFSA-N R-mevalonolactone, (-)- Chemical class C[C@@]1(O)CCOC(=O)C1 JYVXNLLUYHCIIH-ZCFIWIBFSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
235000011054 acetic acid Nutrition 0.000 description 1
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
125000005336 allyloxy group Chemical group 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
239000006286 aqueous extract Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
238000011914 asymmetric synthesis Methods 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
PVYPHUYXKVVURH-UHFFFAOYSA-N boron;2-methylpropan-2-amine Chemical compound [B].CC(C)(C)N PVYPHUYXKVVURH-UHFFFAOYSA-N 0.000 description 1
239000012267 brine Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000013058 crude material Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000004744 fabric Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
150000002440 hydroxy compounds Chemical class 0.000 description 1
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
208000020346 hyperlipoproteinemia Diseases 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 1
238000002955 isolation Methods 0.000 description 1
239000007788 liquid Substances 0.000 description 1
ITYJDNHFRZSTJY-UHFFFAOYSA-N methanesulfonyl bromide Chemical compound CS(Br)(=O)=O ITYJDNHFRZSTJY-UHFFFAOYSA-N 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
150000002912 oxalic acid derivatives Chemical class 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
150000003254 radicals Chemical group 0.000 description 1
230000007017 scission Effects 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000012418 sodium perborate tetrahydrate Substances 0.000 description 1
IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000012265 solid product Substances 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C223/00—Compounds containing amino and —CHO groups bound to the same carbon skeleton
- C07C223/02—Compounds containing amino and —CHO groups bound to the same carbon skeleton having amino groups bound to acyclic carbon atoms of the carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/42—Unsaturated compounds containing hydroxy or O-metal groups
- C07C59/48—Unsaturated compounds containing hydroxy or O-metal groups containing six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/12—Radicals substituted by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an alkyl or cycloalkyl radical attached to the ring nitrogen atom

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
Obesity (AREA)
Diabetes (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Hematology (AREA)
Veterinary Medicine (AREA)
Oil, Petroleum & Natural Gas (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Pyrane Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Steroid Compounds (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

SK5797-89A 1988-10-13 1989-10-12 Erythro-(e)-3,5-dihydroxy-7-[3'-(4''-fluorophenyl)-1'-(1''- -methylethyl)indol-2'-yl]-hept-6-enoic acid and process for preparing thereof SK579789A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US25747588A	1988-10-13	1988-10-13
US35553189A	1989-05-22	1989-05-22

Publications (2)

Publication Number	Publication Date
SK280845B6 SK280845B6 (sk)	2000-08-14
SK579789A3 true SK579789A3 (en)	2000-08-14

Family

ID=26945992

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK5797-89A SK579789A3 (en)	1988-10-13	1989-10-12	Erythro-(e)-3,5-dihydroxy-7-[3'-(4''-fluorophenyl)-1'-(1''- -methylethyl)indol-2'-yl]-hept-6-enoic acid and process for preparing thereof

Country Status (24)

Country	Link
EP (2)	EP0562643A3 (fr)
JP (1)	JP2853227B2 (fr)
KR (1)	KR0162656B1 (fr)
AT (1)	ATE99281T1 (fr)
AU (1)	AU636122B2 (fr)
BG (1)	BG60555B1 (fr)
CA (1)	CA2000553C (fr)
CZ (1)	CZ283316B6 (fr)
DE (1)	DE68911834T2 (fr)
DK (1)	DK175073B1 (fr)
ES (1)	ES2060712T3 (fr)
FI (1)	FI98063C (fr)
HK (1)	HK49496A (fr)
HU (1)	HU207993B (fr)
IE (2)	IE63477B1 (fr)
IL (1)	IL91941A (fr)
MY (1)	MY105067A (fr)
NO (1)	NO174623C (fr)
NZ (1)	NZ230973A (fr)
RO (1)	RO109732B1 (fr)
SG (1)	SG139553A1 (fr)
SK (1)	SK579789A3 (fr)
WO (1)	WO1990003962A1 (fr)
YU (1)	YU48466B (fr)

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US5118853A (en) *	1988-10-13	1992-06-02	Sandoz Ltd.	Processes for the synthesis of 3-disubstituted aminoacroleins
US5290946A (en) *	1988-10-13	1994-03-01	Sandoz Ltd.	Processes for the synthesis of 3-(substituted indolyl-2-yl)propenaldehydes
US5112819A (en) *	1989-10-10	1992-05-12	Glaxo Group Limited	Imidazole derivatives, pharmaceutical compositions and use
DE4424525A1 (de) *	1994-07-12	1995-01-26	Elmar Meyer	Dauermagnet-Kolbenmotor
GT199800127A (es)	1997-08-29	2000-02-01		Combinaciones terapeuticas.
PL353199A1 (en)	1999-08-30	2003-11-03	Aventis Pharma Deutschland Gmbh	Use of inhibitors of the renin-angiotensin system in the prevention of cardiovascular events
CN1217930C (zh)	2000-05-26	2005-09-07	西巴特殊化学品控股有限公司	吲哚衍生物的制备方法和该方法的中间体
US7777006B2 (en)	2002-12-31	2010-08-17	Csl Behring L.L.C.	Method for purification of alpha-1-antitrypsin
EP1623976A4 (fr) *	2003-04-24	2008-07-30	Daicel Chem	Procede pour separer des esters d'acide dihydroxy-heptenoique optiquement actifs
KR20070092994A (ko)	2003-06-18	2007-09-14	테바 파마슈티컬 인더스트리즈 리미티드	플루바스타틴 나트륨 결정형 ｘｉｖ, ｌｘｘｉｉｉ,ｌｘｘｉｘ, ｌｘｘｘ 및 ｌｘｘｘｖｉｉ, 이의 제조 방법,이를 포함하는 조성물 및 이를 사용하는 방법
US7368581B2 (en)	2003-06-18	2008-05-06	Teva Pharmaceutical Industries Ltd.	Process for the preparation of fluvastatin sodium crystal from XIV
US7368468B2 (en)	2003-06-18	2008-05-06	Teva Pharmaceutical Industries Ltd.	Fluvastatin sodium crystal forms XIV, LXXIII, LXXIX, LXXX and LXXXVII, processes for preparing them, compositions containing them and methods of using them
WO2005053683A1 (fr)	2003-11-26	2005-06-16	Duke University	Technique de prevention ou de traitement du glaucome
US7851624B2 (en)	2003-12-24	2010-12-14	Teva Pharamaceutical Industries Ltd.	Triol form of rosuvastatin and synthesis of rosuvastatin
US20060211752A1 (en)	2004-03-16	2006-09-21	Kohn Leonard D	Use of phenylmethimazoles, methimazole derivatives, and tautomeric cyclic thiones for the treatment of autoimmune/inflammatory diseases associated with toll-like receptor overexpression
US7741317B2 (en)	2005-10-21	2010-06-22	Bristol-Myers Squibb Company	LXR modulators
US7888376B2 (en)	2005-11-23	2011-02-15	Bristol-Myers Squibb Company	Heterocyclic CETP inhibitors
ES2327668T3 (es)	2006-04-20	2009-11-02	F.I.S. Fabbrica Italiana Sintetici S.P.A.	Procedimiento para la preparacion de sal sodica de fluvastatina.
EP2327682A1 (fr)	2009-10-29	2011-06-01	KRKA, D.D., Novo Mesto	Utilisation de composés amphiphiles pour la crystallisation controlée de statines et d'intermediaires de statines.
WO2010069593A1 (fr)	2008-12-19	2010-06-24	Krka, D. D., Novo Mesto	Utilisation de composés amphiphiles pour la cristallisation régulée de statines et d'intermédiaires de statines
AU2013214693B2 (en)	2012-02-02	2017-02-23	Kenneth Gek-Jin OOI	Improvements in tear film stability
MX2015014666A (es)	2013-04-17	2016-03-01	Pfizer	Derivados de n-piperidin-3-ilbenzamida para tratar enfermedades cardiovasculares.
WO2016055901A1 (fr)	2014-10-08	2016-04-14	Pfizer Inc.	Composés d'amide substitué
SG11202107614PA (en)	2019-01-18	2021-08-30	Astrazeneca Ab	Pcsk9 inhibitors and methods of use thereof
WO2025168652A1 (fr)	2024-02-05	2025-08-14	Astrazeneca Ab	Azd-0780 en combinaison avec une statine à utiliser pour faire baisser les taux de ldl-c et traiter des maladies cardiovaculaires
TW202539678A (zh)	2024-03-20	2025-10-16	瑞典商阿斯特捷利康公司	Ｐｃｓｋ９抑制劑及其使用方法
TW202602886A (zh)	2024-03-20	2026-01-16	瑞典商阿斯特捷利康公司	Ｐｃｓｋ９抑制劑及其使用方法
TW202602866A (zh)	2024-03-20	2026-01-16	瑞典商阿斯特捷利康公司	Ｐｃｓｋ９抑制劑及其使用方法
WO2025238159A1 (fr)	2024-05-16	2025-11-20	Astrazeneca Ab	Polythérapie comprenant de l'azd0780 et de l'ézétimibe

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GB945536A (en) *	1961-09-08	1964-01-02	Istituto Chemioterapico	Method of preparing ª -amino-acroleins
HU204253B (en) *	1982-11-22	1991-12-30	Sandoz Ag	Process for producing mevalonolactone analogues and derivatives and pharmaceutical compositions containing them
US4739073A (en) *	1983-11-04	1988-04-19	Sandoz Pharmaceuticals Corp.	Intermediates in the synthesis of indole analogs of mevalonolactone and derivatives thereof
US4571428A (en) *	1983-07-08	1986-02-18	Sandoz, Inc.	6-Substituted-4-hydroxy-tetrahydropyran-2-ones
US4650890A (en) *	1984-04-03	1987-03-17	Sandoz Corp.	Preparation of olefinic compounds and intermediates thereof
FI860755A0 (fi) *	1984-06-22	1986-02-20	Sandoz Ag	Pyrazolanaloger av mevolonolakton och deras derivat, foerfaranden foer deras framstaellning samt deras andvaendning.
EP0216785B1 (fr) *	1984-12-04	1991-01-30	Sandoz Ag	Analogues indenes de mevalonolactones et leurs derives
US4668794A (en) *	1985-05-22	1987-05-26	Sandoz Pharm. Corp.	Intermediate imidazole acrolein analogs
JPS6322056A (ja) *	1986-04-30	1988-01-29	サンド・アクチエンゲゼルシヤフト	オレフイン性化合物の製造法
NZ221717A (en) *	1986-09-10	1990-08-28	Sandoz Ltd	Azaindole and indolizine derivatives and pharmaceutical compositions

1989
- 1989-10-11 WO PCT/EP1989/001201 patent/WO1990003962A1/fr not_active Ceased
- 1989-10-11 ES ES89118906T patent/ES2060712T3/es not_active Expired - Lifetime
- 1989-10-11 SG SG200602066-3A patent/SG139553A1/en unknown
- 1989-10-11 AU AU43448/89A patent/AU636122B2/en not_active Expired
- 1989-10-11 EP EP19930106005 patent/EP0562643A3/en not_active Ceased
- 1989-10-11 KR KR1019900701243A patent/KR0162656B1/ko not_active Expired - Lifetime
- 1989-10-11 JP JP1510605A patent/JP2853227B2/ja not_active Expired - Lifetime
- 1989-10-11 DE DE68911834T patent/DE68911834T2/de not_active Expired - Lifetime
- 1989-10-11 AT AT89118906T patent/ATE99281T1/de not_active IP Right Cessation
- 1989-10-11 IE IE327789A patent/IE63477B1/en not_active IP Right Cessation
- 1989-10-11 RO RO145326A patent/RO109732B1/ro unknown
- 1989-10-11 IE IE940109A patent/IE940109L/xx unknown
- 1989-10-11 YU YU197389A patent/YU48466B/sh unknown
- 1989-10-11 IL IL9194189A patent/IL91941A/en not_active IP Right Cessation
- 1989-10-11 HU HU896048A patent/HU207993B/hu unknown
- 1989-10-11 MY MYPI89001403A patent/MY105067A/en unknown
- 1989-10-11 EP EP89118906A patent/EP0363934B1/fr not_active Expired - Lifetime
- 1989-10-11 NZ NZ230973A patent/NZ230973A/xx unknown
- 1989-10-12 CZ CS895797A patent/CZ283316B6/cs not_active IP Right Cessation
- 1989-10-12 SK SK5797-89A patent/SK579789A3/sk unknown
- 1989-10-12 CA CA002000553A patent/CA2000553C/fr not_active Expired - Lifetime
1990
- 1990-06-07 BG BG92179A patent/BG60555B1/bg unknown
- 1990-06-12 FI FI902935A patent/FI98063C/fi active IP Right Grant
- 1990-06-12 NO NO902598A patent/NO174623C/no unknown
- 1990-06-13 DK DK199001446A patent/DK175073B1/da not_active IP Right Cessation
1996
- 1996-03-21 HK HK49496A patent/HK49496A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
RO109732B1 (ro)	1995-05-30
YU197389A (en)	1990-12-31
JP2853227B2 (ja)	1999-02-03
ES2060712T3 (es)	1994-12-01
AU636122B2 (en)	1993-04-22
KR900701723A (ko)	1990-12-04
HK49496A (en)	1996-03-29
NO174623B (no)	1994-02-28
DK144690A (da)	1990-06-13
SG139553A1 (en)	2008-02-29
IE893277L (en)	1990-04-13
CA2000553A1 (fr)	1990-04-13
IE63477B1 (en)	1995-04-19
JPH03501735A (ja)	1991-04-18
CZ579789A3 (en)	1997-11-12
KR0162656B1 (ko)	1999-01-15
FI902935A0 (fi)	1990-06-12
NZ230973A (en)	1993-03-26
FI98063C (fi)	1997-04-10
ATE99281T1 (de)	1994-01-15
NO902598L (no)	1990-08-07
AU4344889A (en)	1990-05-01
HU207993B (en)	1993-07-28
DE68911834D1 (de)	1994-02-10
IL91941A (en)	1994-10-21
EP0363934A1 (fr)	1990-04-18
HUT53860A (en)	1990-12-28
NO902598D0 (no)	1990-06-12
HU896048D0 (en)	1990-11-28
BG60555B1 (en)	1995-08-28
YU48466B (sh)	1998-08-14
EP0562643A3 (en)	1994-05-18
DK144690D0 (da)	1990-06-13
EP0562643A2 (fr)	1993-09-29
DK175073B1 (da)	2004-05-24
FI98063B (fi)	1996-12-31
CZ283316B6 (cs)	1998-02-18
NO174623C (no)	1994-06-08
CA2000553C (fr)	2001-12-04
IL91941A0 (en)	1990-06-10
IE940109L (en)	1990-04-13
BG92179A (bg)	1993-12-24
DE68911834T2 (de)	1994-06-23
WO1990003962A1 (fr)	1990-04-19
SK280845B6 (sk)	2000-08-14
EP0363934B1 (fr)	1993-12-29
MY105067A (en)	1994-07-30

Publication	Publication Date	Title
SK579789A3 (en)	2000-08-14	Erythro-(e)-3,5-dihydroxy-7-[3'-(4''-fluorophenyl)-1'-(1''- -methylethyl)indol-2'-yl]-hept-6-enoic acid and process for preparing thereof
US5189164A (en)	1993-02-23	Processes for the synthesis of syn-(E)-3,5-dihydroxy-7-substituted hept-6-enoic and heptanoic acids and derivatives and intermediates thereof
KR900001212B1 (ko)	1990-02-28	메바로노락톤 및 그것의 유도체의 헤테로사이클릭 유사체 및 그것의 생산방법 및 약학적인 그것의 용도
KR20040077883A (ko)	2004-09-07	유기 화합물의 제조 방법
US6743926B2 (en)	2004-06-01	Process for the preparation of indole derivatives and intermediates of the process
KR20040081161A (ko)	2004-09-20	ＨＭＧ-ＣｏＡ 환원효소 억제제의 제조 방법
CN102858787A (zh)	2013-01-02	双磷酸化合物及使用其的不对称反应
EP1478650B1 (fr)	2009-09-30	Nouveaux esters de boronate
EP0367895A1 (fr)	1990-05-16	Hydroxyacides substitués par un groupe pyrimidique, lactones, esters et compositions pharmaceutiques les contenant
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