KR880013959A - 인 함유 HMG-CoA 리덕타아제 억제제, 신규 중간체 및 방법 - Google Patents
인 함유 HMG-CoA 리덕타아제 억제제, 신규 중간체 및 방법 Download PDFInfo
- Publication number
- KR880013959A KR880013959A KR1019880006019A KR880006019A KR880013959A KR 880013959 A KR880013959 A KR 880013959A KR 1019880006019 A KR1019880006019 A KR 1019880006019A KR 880006019 A KR880006019 A KR 880006019A KR 880013959 A KR880013959 A KR 880013959A
- Authority
- KR
- South Korea
- Prior art keywords
- group
- hydroxybutanoic acid
- hydroxyphosphinyl
- methyl ester
- phenyl
- Prior art date
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- 238000000034 method Methods 0.000 title claims 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 title 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title 1
- 239000000543 intermediate Substances 0.000 title 1
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims 29
- 150000002503 iridium Chemical class 0.000 claims 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 24
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 20
- 150000004702 methyl esters Chemical class 0.000 claims 20
- -1 cinnamil Chemical group 0.000 claims 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 13
- 125000003545 alkoxy group Chemical group 0.000 claims 10
- 235000010290 biphenyl Nutrition 0.000 claims 10
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 9
- 150000001875 compounds Chemical class 0.000 claims 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 9
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 8
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims 8
- 150000003839 salts Chemical class 0.000 claims 8
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims 7
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 7
- 125000005647 linker group Chemical group 0.000 claims 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 6
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims 6
- 125000005843 halogen group Chemical group 0.000 claims 5
- 230000002209 hydrophobic effect Effects 0.000 claims 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 5
- 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 claims 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims 4
- 150000002148 esters Chemical class 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims 3
- 239000002253 acid Substances 0.000 claims 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims 3
- 239000003960 organic solvent Substances 0.000 claims 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
- 102000004190 Enzymes Human genes 0.000 claims 2
- 108090000790 Enzymes Proteins 0.000 claims 2
- FIWPPDZSFQZMIK-UHFFFAOYSA-N OP(O)([ClH](O)(=O)=O)=O Chemical compound OP(O)([ClH](O)(=O)=O)=O FIWPPDZSFQZMIK-UHFFFAOYSA-N 0.000 claims 2
- 150000001450 anions Chemical class 0.000 claims 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 2
- 125000001246 bromo group Chemical group Br* 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 235000012000 cholesterol Nutrition 0.000 claims 2
- 238000001816 cooling Methods 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 229910052739 hydrogen Inorganic materials 0.000 claims 2
- 125000003003 spiro group Chemical group 0.000 claims 2
- DLNAOSNXEVENKA-LFUZPPSTSA-N (3s)-3-hydroxy-4-[methoxy-[2-(2-phenylphenyl)ethyl]phosphoryl]butanoic acid Chemical compound OC(=O)C[C@H](O)CP(=O)(OC)CCC1=CC=CC=C1C1=CC=CC=C1 DLNAOSNXEVENKA-LFUZPPSTSA-N 0.000 claims 1
- QJKCWZDFMJKJPG-KRWDZBQOSA-N (3s)-4-[2-(2,4-dimethyl-6-phenylphenyl)ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)C(C=2C=CC=CC=2)=C1 QJKCWZDFMJKJPG-KRWDZBQOSA-N 0.000 claims 1
- IFXNYSIUJLZFNH-IBGZPJMESA-N (3s)-4-[2-[1-(4-fluorophenyl)-3-methylnaphthalen-2-yl]ethynyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)C#CC=1C(C)=CC2=CC=CC=C2C=1C1=CC=C(F)C=C1 IFXNYSIUJLZFNH-IBGZPJMESA-N 0.000 claims 1
- ZDXISXLUXINJAK-SFHVURJKSA-N (3s)-4-[2-[1-(4-fluorophenyl)-3-propan-2-ylindol-2-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C12=CC=CC=C2C(C(C)C)=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)N1C1=CC=C(F)C=C1 ZDXISXLUXINJAK-SFHVURJKSA-N 0.000 claims 1
- ADKZUWSCAPWKIF-STFFIMJZSA-N (3s)-4-[2-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]ethynyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(=O)(OC)C#CC1=C(C)C=C(C)C=C1C1=CC=C(F)C(C)=C1 ADKZUWSCAPWKIF-STFFIMJZSA-N 0.000 claims 1
- YDVMHDBSWBXHQO-SFHVURJKSA-N (3s)-4-[2-[2-[(4-fluorophenyl)methoxy]-4,6-dimethylphenyl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)C(OCC=2C=CC(F)=CC=2)=C1 YDVMHDBSWBXHQO-SFHVURJKSA-N 0.000 claims 1
- RXCROTMPEYLNLM-SFHVURJKSA-N (3s)-4-[2-[2-[(4-fluorophenyl)methoxy]-4,6-dimethylphenyl]ethynyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(C#CP(O)(=O)C[C@@H](O)CC(O)=O)C(OCC=2C=CC(F)=CC=2)=C1 RXCROTMPEYLNLM-SFHVURJKSA-N 0.000 claims 1
- IGODFPWSBOIKCY-FQEVSTJZSA-N (3s)-4-[2-[3-(4-fluorophenyl)-1-phenyl-5-propan-2-ylpyrazol-4-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=C(CCP(O)(=O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=NN1C1=CC=CC=C1 IGODFPWSBOIKCY-FQEVSTJZSA-N 0.000 claims 1
- JAFCYEUATIWTEN-FQEVSTJZSA-N (3s)-4-[2-[3-(4-fluorophenyl)-1-phenyl-5-propan-2-ylpyrazol-4-yl]ethynyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC(C)C1=C(C#CP(O)(=O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=NN1C1=CC=CC=C1 JAFCYEUATIWTEN-FQEVSTJZSA-N 0.000 claims 1
- IIMSXNXPALOVBL-SFHVURJKSA-N (3s)-4-[2-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C12=CC=CC=C2N(C(C)C)C(CCP(O)(=O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 IIMSXNXPALOVBL-SFHVURJKSA-N 0.000 claims 1
- IJVGUKDIBVACFH-WABSOPGISA-N (3s)-4-[2-[3-(4-fluorophenyl)-2-phenyl-5-propan-2-ylimidazol-4-yl]ethyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C=1C=C(F)C=CC=1N1C(CCP(=O)(OC)C[C@@H](O)CC(O)=O)=C(C(C)C)N=C1C1=CC=CC=C1 IJVGUKDIBVACFH-WABSOPGISA-N 0.000 claims 1
- ZKDMUYYXZBOQTI-WABSOPGISA-N (3s)-4-[2-[3-(4-fluorophenyl)-2-phenyl-5-propan-2-ylimidazol-4-yl]ethynyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C=1C=C(F)C=CC=1N1C(C#CP(=O)(C[C@@H](O)CC(O)=O)OC)=C(C(C)C)N=C1C1=CC=CC=C1 ZKDMUYYXZBOQTI-WABSOPGISA-N 0.000 claims 1
- KFMWRSMTOMOJGE-WABSOPGISA-N (3s)-4-[2-[4-(4-fluorophenyl)-5-phenyl-2-propan-2-ylpyrazol-3-yl]ethynyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound N=1N(C(C)C)C(C#CP(=O)(C[C@@H](O)CC(O)=O)OC)=C(C=2C=CC(F)=CC=2)C=1C1=CC=CC=C1 KFMWRSMTOMOJGE-WABSOPGISA-N 0.000 claims 1
- ZKRWBLMONAGUHZ-WABSOPGISA-N (3s)-4-[2-[5-(4-fluorophenyl)-1-phenyl-3-propan-2-ylpyrazol-4-yl]ethyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(=O)(OC)CCC=1C(C(C)C)=NN(C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 ZKRWBLMONAGUHZ-WABSOPGISA-N 0.000 claims 1
- DRODFEOUKUXQER-FQEVSTJZSA-N (3s)-4-[2-[5-(4-fluorophenyl)-1-phenyl-3-propan-2-ylpyrazol-4-yl]ethynyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)C#CC=1C(C(C)C)=NN(C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 DRODFEOUKUXQER-FQEVSTJZSA-N 0.000 claims 1
- NXLGKVBKTRBMTB-WABSOPGISA-N (3s)-4-[2-[5-(4-fluorophenyl)-1-phenyl-3-propan-2-ylpyrazol-4-yl]ethynyl-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(=O)(OC)C#CC=1C(C(C)C)=NN(C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 NXLGKVBKTRBMTB-WABSOPGISA-N 0.000 claims 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- WHBMMWSBFZVSSR-VKHMYHEASA-N (S)-3-hydroxybutyric acid Chemical compound C[C@H](O)CC(O)=O WHBMMWSBFZVSSR-VKHMYHEASA-N 0.000 claims 1
- IWSQAUQTGRBEQX-SFHVURJKSA-N 2-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]ethyl-[(2S)-2-hydroxy-4-methoxy-4-oxobutyl]phosphinic acid Chemical compound COC(C[C@@H](CP(=O)(O)CCC1=C(C=C(C=C1C)C)C1=CC(=C(C=C1)F)C)O)=O IWSQAUQTGRBEQX-SFHVURJKSA-N 0.000 claims 1
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical compound CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 claims 1
- GVSTYPOYHNVKHY-UHFFFAOYSA-N 2-methoxybutanoic acid Chemical compound CCC(OC)C(O)=O GVSTYPOYHNVKHY-UHFFFAOYSA-N 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 102100029077 3-hydroxy-3-methylglutaryl-coenzyme A reductase Human genes 0.000 claims 1
- 101710158485 3-hydroxy-3-methylglutaryl-coenzyme A reductase Proteins 0.000 claims 1
- AAQMQVNMIKIIFW-UHFFFAOYSA-N 4-[2-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CCP(O)(=O)CC(O)CC(O)=O)C(C=2C=C(C)C(F)=CC=2)=C1 AAQMQVNMIKIIFW-UHFFFAOYSA-N 0.000 claims 1
- QFVOVARNXVZLKL-UHFFFAOYSA-N 4-[2-[2-(cyclohexylmethyl)-4,6-dimethylphenyl]ethenyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(C=CP(O)(=O)CC(O)CC(O)=O)C(CC2CCCCC2)=C1 QFVOVARNXVZLKL-UHFFFAOYSA-N 0.000 claims 1
- PZRJNNIVYSSRMG-VOTSOKGWSA-N 4-[[(e)-2-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(\C=C\P(O)(=O)CC(O)CC(O)=O)C(C=2C=C(C)C(F)=CC=2)=C1 PZRJNNIVYSSRMG-VOTSOKGWSA-N 0.000 claims 1
- VGMAQMNSFKRDER-VAWYXSNFSA-N 4-[[(e)-2-[3-(4-fluorophenyl)-1-propan-2-ylindol-2-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound C12=CC=CC=C2N(C(C)C)C(\C=C\P(O)(=O)CC(O)CC(O)=O)=C1C1=CC=C(F)C=C1 VGMAQMNSFKRDER-VAWYXSNFSA-N 0.000 claims 1
- PZUMNTHIHVFVEB-OUKQBFOZSA-N 4-[[(e)-2-[5-(4-fluorophenyl)-1-phenyl-3-propan-2-ylpyrazol-4-yl]ethenyl]-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)CC(O)CP(O)(=O)/C=C/C=1C(C(C)C)=NN(C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 PZUMNTHIHVFVEB-OUKQBFOZSA-N 0.000 claims 1
- KLIAJVJCJXRUFP-KRWDZBQOSA-N C=1C=CC=CC=1[Si](O[C@@H](CC(O)=O)CP(=O)OCO)(C(C)(C)C)C1=CC=CC=C1 Chemical compound C=1C=CC=CC=1[Si](O[C@@H](CC(O)=O)CP(=O)OCO)(C(C)(C)C)C1=CC=CC=C1 KLIAJVJCJXRUFP-KRWDZBQOSA-N 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims 1
- AYVGBNGTBQLJBG-UHFFFAOYSA-N [3-(hydroxymethyl)cyclopentyl]methanol Chemical compound OCC1CCC(CO)C1 AYVGBNGTBQLJBG-UHFFFAOYSA-N 0.000 claims 1
- 125000002252 acyl group Chemical group 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000004305 biphenyl Substances 0.000 claims 1
- 239000004202 carbamide Substances 0.000 claims 1
- 125000001589 carboacyl group Chemical group 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 229950004696 flusalan Drugs 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 125000005059 halophenyl group Chemical group 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
- 230000000055 hyoplipidemic effect Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 claims 1
- 229910003002 lithium salt Inorganic materials 0.000 claims 1
- 159000000002 lithium salts Chemical class 0.000 claims 1
- 125000004043 oxo group Chemical group O=* 0.000 claims 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 125000004437 phosphorous atom Chemical group 0.000 claims 1
- 229910052698 phosphorus Inorganic materials 0.000 claims 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 239000000758 substrate Substances 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/302—Acyclic unsaturated acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/303—Cycloaliphatic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
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Abstract
내용 없음
Description
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Claims (10)
- 하기 구조식의 부분을 갖는 효소 3-히드록시-3-메틸 글루타릴-죠효소 A리덕타이제를 억제하는데 유용한 화합물.식중, X는 -CH2-, -CH2-, -CH=CH-, -CH2CH2CH2-, -C=C- 또는 -CH2O-기(여기에서, O는 Z에 결합됨)이고, Z는 수소성 결합기임.
- 제 1 항에 있어서, 소수성 결합기기 호지성(lipophilic)기이고, 이 기는 적당한 연결자(X)에 의해 분자의 HMG와 유사한 상부 측쇄에 연결된 경우, 기질 HMG CoA의 결합에 사용되지 않는 효소의 수소성 포켓에 결합되여 Z=H인 화합물에 대한 효능을 증대시키는 화합물.
- 제 1 항에 있어서, 하기 구조식을 갖고, 유리산, 생리학적으로 가수분해될 수 있는 에스테르 및 생리학적으로 허용되는 에스테르형이거나, 또는 염의 형태인 화합물.상기 식중, R은 OH 또는 저급 알콕시기이고, RX는 H원자 또는 저급 알킬기이고, X는 CH2, -CH2CH2-, -CH2CH2CH-, CH=CH-, -C=C- 또는 -CH2O기(여기에서, O는 Z에 결합됨)이고, Z는 다음과 같은 소수성 결합기이다.상기 식중, R1, R2, R2a및 R2b는 서로 동일하거나 또는 상이한 것으로서, 각각 독립적으로 H원자, 할로겐원자, 저급알킬, 할로알킬, 페닐, 치환페닐 또는 ORy기(여기에서, Ry는 H원자, 알카노일, 벤조일, 페닐, 할로페닐, 페닐-저급 알킬, 신나밀, 할로알킬, 알릴, 시클로알킬- 저급 알킬, 아다만틸-저급 알킬 또는 치환 페닐-저급 알킬기임)에서 선택된 기이고, Z가 하기 구조식의 기인 경우,R5및 R5'는 서로 동일하거나 또는 상이한 것으로서, H원자, 저급 알킬 또는 OH기이고, R6은 저급 알킬기, 예를 들면(여기에서, R7은 H원자 또는 저급 알킬기임), 또는 아릴CH2-기이고, R6a는 저급 알킬, 히드록시, 옥소기 또는 할로겐 원자이고, q는 0, 1, 2, 또는 3이고, Z가 하기 구조식또는의 기인 경우, R3및 R4중 하나는기 (식중, R13은 수소원자, 저급알킬, t-부톡시기를 제외한 저급 알콕시기, 할로겐원자, 페녹시 또는 벤질록시기이고, R14는 수소원자, 저급알킬, 저급 알콕시기, 할로겐원자, 페녹시 또는 벤질옥시기이고, R14a는 수소원자, 저급알킬, 저급알콕시기, 또는 할로겐원자이고, 단, R13이 수소원자인 경우에 R14및 R14a는 모두 수소 원자이어야 하고, R14가 소수원자인 경우에 R14a는 수소원자이어야하고, R13및 R14중 겨우 1개는 트리플루오로메틸, 페녹시 또는 벤질옥시기임)이고, 다른 하나는 저급 알킬, 시클로알킬 또는 페닐-(CH2)p-기 (여기에서, P는 0, 1, 2, 3 또는 4임)이고, R8은 수소원자, C1-4알킬, C3-6시클로알킬, t-부톡시기를 제외한 C1-4알콕시기, 트리플루오로메틸기, 플루오로, 클로로원자, 페녹시 또는 벤질옥시기이고, R9는 수소원자, C1-3알킬, C1-3알콕시, 트리플루오로메틸기, 플루오로, 클로로원자, 페녹시 또는 벤질옥시기이되, 단 R8이 수소 원자인 경우 R9는 수소원자이어야 하고, R8및 R9중 겨우 1개는 트리플루오로메틸, 페녹시, 또는 벤질옥시기이고, R10및 R11은 독립적으로 수소원자, 알킬, 시클로알킬, 아다만틸-1 또는기 (식중, R13, R14및 R14a는 상기 정의한 바와 같고, q=0, 1, 2, 3 또는 4임)이고, Y는 O, S 원자 또는 N-R10기이고; Z가 하기 구조식의 기인 경우,Ra는 수소원자, 또는 일급 또는 이급 1-6C알킬기이고, Rb는 일급 또는 이급 1-6C 알킬기이거나, 또는 Ra+Rb는 (CH2)r(여기에서, r=2, 3, 4, 5 또는 6) 또는 (시스)-CH2-CH=CH-CH2기이고, R8및 R9는 상기 정의한 바와 같으며, R12는 저급 알킬, 시클로알킬기 또는기 (식중, R13, R14및 R14a는 상기 정의한 바와 같음)이고; Z가 하기 구조식의 기인 경우R15및 R16은 모두 H, Cl, Br원자, CN, CF3, 페닐, 1-4C알킬, 2-8C알콕시카르보닐, -CH2OR17또는 -CH2OCONHR18기 (여기에서, R17은 H원자 또는 1-6C알카노일기이고, R18은 알킬기, 또는 F, Cl, Br원자 또는 1-4C알킬기에 의해 임으로 치환된 페닐기임)이거나, 또는 R15및 R16은 함께 -(CH2)S-, -CH2OCH2-, -CON(R19) CO-, 또는 -CON(R20)N(R21)CO-기 (여기에서, S=3 또는 4이고, R19=H원자, 1-6C알킬, 페닐 또는 벤질기이고, R20및 R21은 H원자, 1-4C알킬 또는 벤질기임)이고, X는 -CH2-, -CH2CH2- 또는 -CH2CH2CH2기이고 ; Z가 하기 구조식의 기인 경우,R22는 저금 알킬, 시클로알킬, 아다만틸-1 또는기(여기에서, t=1,2,3 또는 4임)이고, R23및 R23a는 서로 동일하거나 또는 상이한 것으로서, 각각 독립적으로 수소원자, 저급알킬, t-부톡시기를 제외한 저급 알콕시기, 할로겐원자, 페녹시 또는 벤질 옥시기이고, 단, R23이 수소원자인 경우 R23a는 수소원자이어야 하고, R23및 R23a중 겨우 1개는 트리플루오로메틸, 페녹시 또는 벤질옥시기이고 ; X가 -CH2O-기(탄소 원자가 P에 결합되고, O원자는 Z기와 결합됨)인 경우, 소수성 결합기, 즉 Z는 하기 구조식의 기또는(식중, RX는 수소 원자 또는 저급 알킬기임)임.
- 제 3 항에 있어서, X가 -CH=CH- 또는 -C=C-기이고, R이 OH 또는 알콕시기이고, Z가또는기인 화합물.
- 제 1 항에 있어서, 다음과 같이 명명되는 화합물.(S)-4-[[(E_-2-[4'-플루오로-3, 3', 5-트리메틸[1, 1'-비페닐]-2-일]에테닐]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염, (S)-4-[[2-[4'-플루오로-3, 3', 5-트리메틸[1,1'-비페닐]-2-일]에틸]히드록시포스피닐]-3-히드록시부탄산 메틸 에스테르 또는 그의 모노-또는 디-알칼리금속염, (S)-4-[[[4'-플루오로-3, 3', 5-트리메틸[1,1'-비페닐]-2-일]에티닐]메톡시포스피닐]-3-히드록시부탄산, 또는 그의 메틸에스테르, (5Z)-4-[[-2-[4'-플루오로-3, 3', 5-트리메틸[1,1'-비페닐]-2-일]에테닐]히드록시포스피닐]-3-히드록시부탄산, 또는 그의 에스테르, (S)-4-[[2-[3, (4-플루오로)-1-(1-메틸에틸)-1H-인돌-2-일]에틸]메톡시포스피닐]-3-히드록시부탄산, 메틸 세트테르, (S)-4-[[2-[[1, 1'-비페닐]-2-일]에틸]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (S)-4-[[2-[4'-플루오로-3, 3', 5-트리메틸[1, 1'-비페닐]-2-일]에틸]히드록시포스피닐]-3-히드록시부탄산, 이리튬염, (5Z)-4-[[2-[4'-플루오로-3, 3', 5-트리메틸[1, 1'-비페닐]-2-일]에테닐]히드록시포스피닐]-3-히드록시부탄산, 이리튬염, (5Z)-4-[[2-[4'-플루오로-3,3',5-트리메틸[1,1'-비페닐]-2-일]에테닐]히드록시포스피닐]-3-히드록시부탄산,(S)-4-[[2-[3-(4-플루오로페닐)-1-(1-메틸에틸)-1H-인돌-2-일]에틸]히드록시포스피닐]-3-히드록시부탄산,이리튬염, (S)-4-[[2-[[1, 1'-비페닐]-2-일]에틸]히드록시포스피닐]-3-부탄산 이리튬염, (S)-4-(히드록시메톡시포스피닐)-3-[[(1, 1-디메틸에틸)디페닐실릴]옥시]부탄산, 메틸 에스테르, 또는 그의 디시클로 헥실아민(1 : 1)염, (S)-4-[[2-[1-(4-플루오로페닐)-3-(1-메틸에틸-1-인돌-2-일]에티닐]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[2-[1-(4-플루오로페닐)-3-(1-메틸에틸)-1H-인돌-2-일]에틸]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (E)-4-[[2-[3-(4-플루오로페닐)-1 -(1-메틸에틸)-1H-인돌-2-일]에테닐]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, 4-[[2-[4'-플루오로-3, 3', 5-트리메틸[1, 1'-비페닐]-2-일]에틸]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (E)-4-[[2-[4'-플루오로-3, 3', 5-트리메틸[1, 1'-비페닐]-2-일]에테닐]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[[2, 4-디메틸-6-[(4-플루오로페닐)메톡시]페닐]에틸]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[[2, 4-디메틸-6-[(4-플루오로페닐)메톡시]페닐]에티닐]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[2-[3, 5-디메틸[1, 1'-비페닐]-2-일]에틸]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[2-[4'-플루오로-3, 5-디메틸[1, 1'-비페닐]-2-일]에틸]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[2-[[1, 1'-비페닐]-2-일]에티닐]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[2-[5-(4-플루오로페닐)-3-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에티닐]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (S)-4-[[2-[5-(4-플루오로페닐)-3-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에티닐]히드록시포스피닐]-3-히드록시부탄산, 이리튬염, (E)-4-[[2-[5-(4-플루오로페닐)-3-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에테닐]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (E)-4-[[2-[5-(4-플루오로페닐)-3-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에테닐]히드록시포스피닐]-3-히드록시부탄산, 이리튬염, (S)-4-[[2-[5-(4-플루오로페닐)-3-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에틸]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (S)-4-[[2-[5-(4-플루오로페닐)-3-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에틸]히드록시포스피닐]-3-히드록시부탄산,이리튬염(S)-4-[[2-3-(4-플루오로페닐)-5-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에틸]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (S)-4-[[2-[3-(4-플루오로페닐)-5-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에틸]히드록시포스피닐]-3-히드록시부탄산, 이리튬염, (S)-4-[[2-[3-(4-플루오로페닐)-5-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에티닐]메톡시부탄산,메틸에스테르,(S)-4-[[2-[3-(4-플루오로페닐)-5-(1-메틸에틸)-1-페닐-1H-피라졸-4-일]에티닐]히드록시포스피닐]-3-히드록시부탄산, 이리튬염, (S)-4-[[[4-(4-플루오로페닐)-1-(1-메틸에틸)-3-페닐-1H-피라졸-5-일]에티닐]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (S)-4-[[[4-(4-플루오로페닐)-1-(1-메틸에틸-3-페닐-1H-피라졸-5-일]에티닐]히드록시포스피닐]-3-히드록시부탄산, 이리튬염, (S)-4-[[2-[4-(4-플루오로페닐)-1-(1-메틸에틸)-3-페닐-1H-피라졸-5-일]에틸]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (S)-4-[[2-[4-(4-플루오로페닐)-1-(1-메틸에틸)-3-페닐-1H-피라졸-5-일]에틸]히드록시포스피닐]-3-히드록시부탄산,이리튬염,(S)-4-[[[1-(4-플루오로페닐)-4-(1-메틸에틸)-2-페닐-1H-이미다졸-5-일]에티닐]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (S)-4-[[[1-(4-플루오로페닐)-4-(1-메틸에틸)-2-페닐-1H-이미다졸-5-일]에티닐]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (S)-4-[[2-[1-(4-플루오로페닐)-4-(1-메틸에틸)-2-페닐-1H-이미다졸-5-일]에틸]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, (S)-4-[[2-[1-(4-플루오로페닐)-4-(1-메틸에틸)-2-페닐-1H-이미다졸-5-일]에틸]히드록시포스피닐]-3-히드록시부탄산, 이리튬염, (S)-4-[[[2-(시클로헥실메틸)-4, 6-디메틸페닐]에티닐]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[2-[2-(시클로헥실메틸)-4, 6-디메틸페닐]에테닐]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, 4-[[2-[2-(시클로헥실메틸)-4, 6-디메틸페닐]에테닐]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[2-[2-(시클로헥실메틸)-4, 6-디메틸페닐]에틸]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, 4-[[[4'-플루오로-3, 3', 5-트리메틸[1, 1'-비페닐]-2-일]옥시]메틸]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, 4-[[[[4'-플루오로-3, 3', 5-트리메틸[1, 1'-비페닐]-2-일]메틸]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[[1-(4-플루오로페닐)-3-메틸-2-나프탈레닐]에티닐]히드록시포스피닐]-3-히드록시부탄산, 또는 그의 이리튬염 또는 그의 메틸 에스테르, (E)-4-[[1-[1-(4-플루오로페닐)-3-메틸-2-나프탈레닐]에테닐]히드록시포스피닐]-3-히드록시부탄산, 또는 그의 이리튬염 또는 그의 메틸 에스테르, (S)-4-[[2-[1-(4-플루오로페닐)-3-메틸-2-나프탈레닐]에틸]히드록시포스피닐]-3-히드록시부탄산 또는 그의 이리튬염 또는 그의 메틸 에스테르, 4-[[3-[4'-플루오로-3, 3', 5-트리메틸-3, 3', 5-트리메틸[1, 1'-비페닐]-2-일]프로필]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, 4-[[3-[4'-플루오로-3, 3', 5-트리메틸[1, 1'-비페닐]-2-일]프로필]히드록시포스피닐]-3-히드록시부탄산 이리튬염, [1S-[1＜a(R), 2＜a, 4a＜b, 8＜b, 8a＜a]]-4-[[2-[8-(2, 2-디메틸-1-옥소부톡시)데카히드로-2-메틸-1-나프탈레닐]에틸]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, [1S-[1＜a(R), 2＜a, 4a＜b, 8＜b, 8a＜a]]-4-[[2-[8-(2, 2-디메틸-1-옥소부톡시)데카히드로-2-메틸-1-나프탈레닐]에틸]메톡시포스피닐]-3-히드록시부탄산, 이리튬염, (S)-4-[[[3'-(4-플루오로페닐)스피로[시클로펜탄-[1, 1'-[1H]인덴]-2-일]에티닐]메톡시포스피닐]-3-히드록시부탄산, 메틸 에스테르, 또는 (S)-4-[[[3'-(4-플루오로페닐)스피로[시클로 펜탄-1, 1'-[1H]인덴]-2-일]에티닐]히드록시포스피닐]-3-히드록시부탄산, 이리튬염.
- 하기 구조식을 갖고, 그의 입체 이성질체 모두를 포함하는 중간체.[식중, Ra'은 알콕시 또는 히드록시기이고, Rb'은 히드록시기, Cl원자, -C=C-Z, -CH2CH2CH2-Z, -CH2O-Z, -CH=CH-Z 또는 -CH2CH2-Z기 (여기에서, Z는 소수성 결합기임)이되, 단 Rb'이 히드록시기인 경우, Ra'은 히드록시 또는 알콕시기임], 또는 하기 구조식을 갖고, 그의 입체 이성질체 모두를 포함하는 중간체.식중, X는 (CH2)a(여기에서, a는 1, 2 또는 3임), -CH=CH-, 또는 -CH2O-기이고, Z는 소수성 결합기임.
- 하기 구조식의(트랜스) 요소드화 비닐을불활성 유기 용매중에서 금속화제로 처리하고, 생성된 음이온을, 불활성 유기 용매 중에서 하기 구조식의 포스포노클로리데이트의 냉각 용액으로 반응시킴을 특징으로 하는, Ra'이 O알킬기이고, Rb'이 -CH=CH-Z기인 제 6 항의 중간체의 제조방법.
- 하기 구조식의 알킬의 포스포노클로리데이트의 냉각 용액을 불활성 유기 용매 중에서 하기 구조식의 이음이온으로 처리시킴을 특징으로 하는 하기 구조식알킬알킬을 갖고, 제 6 항에서 정의한 중간체의 제조방법.
- 제 3 항에 의한 화합물 및 그의 제약상 허용되는 담체로 되는 저콜레스테롤혈성 또는 저지방혈성 조성물.
- 콜레스테롤 생합성의 억제를 위한 제 3 항에 의한 화합물의 용도.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5323887A | 1987-05-22 | 1987-05-22 | |
| US053,238 | 1987-05-22 | ||
| US10968187A | 1987-10-19 | 1987-10-19 | |
| US109681 | 1987-10-19 |
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| Publication Number | Publication Date |
|---|---|
| KR880013959A true KR880013959A (ko) | 1988-12-22 |
Family
ID=26731613
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019880006019A KR880013959A (ko) | 1987-05-22 | 1988-05-21 | 인 함유 HMG-CoA 리덕타아제 억제제, 신규 중간체 및 방법 |
Country Status (24)
| Country | Link |
|---|---|
| JP (1) | JPH01139589A (ko) |
| KR (1) | KR880013959A (ko) |
| CN (1) | CN1030761A (ko) |
| AU (2) | AU610174B2 (ko) |
| BE (1) | BE1002251A3 (ko) |
| CH (3) | CH678626A5 (ko) |
| DE (1) | DE3817298C2 (ko) |
| DK (1) | DK277388A (ko) |
| ES (1) | ES2009919A6 (ko) |
| FI (1) | FI87927C (ko) |
| FR (1) | FR2615516B1 (ko) |
| GB (1) | GB2205838B (ko) |
| GR (1) | GR880100332A (ko) |
| HU (1) | HU201085B (ko) |
| IE (1) | IE63715B1 (ko) |
| IL (1) | IL86463A (ko) |
| IT (1) | IT1217684B (ko) |
| NL (1) | NL8801331A (ko) |
| NO (1) | NO882219L (ko) |
| NZ (1) | NZ224734A (ko) |
| PH (2) | PH25581A (ko) |
| PL (1) | PL157761B1 (ko) |
| PT (1) | PT87540B (ko) |
| SE (3) | SE501541C2 (ko) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO882218L (no) * | 1987-05-22 | 1988-11-23 | Squibb & Sons Inc | Fremgangsmaate for fremstilling av fosforholdige hmg-coa reduktase-inhibitorer. |
| AU637408B2 (en) * | 1989-10-10 | 1993-05-27 | Glaxo Group Limited | Substituted N-vinyl imidazole derivatives. |
| US5124453A (en) * | 1990-03-02 | 1992-06-23 | E. R. Squibb & Sons, Inc. | Process for preparing certain 5,6,7,8-tetrahydroindolizinyl (ethyl or ethynyl)-hydroxy or methoxy-phosphinyl-3-hydroxy-butanoates and derivatives thereof |
| US5025000A (en) * | 1990-03-02 | 1991-06-18 | E. R. Squibb & Sons, Inc. | Phosphorus-containing HMG-CoA reductase inhibitor compounds |
| CA2042526A1 (en) * | 1990-06-11 | 1991-12-12 | Adeoye Y. Olukotun | Method for preventing a second heart attack employing an hmg coa reductase inhibitor |
| CA2043525A1 (en) * | 1990-06-24 | 1991-12-25 | Donald S. Karanewsky | Phosphorus-containing hmg-coa reductase inhibitors, new intermediates and method |
| DE4023308A1 (de) * | 1990-07-21 | 1992-01-23 | Bayer Ag | Substituierte pyrido-oxazine |
| DE4025818A1 (de) * | 1990-08-16 | 1992-02-20 | Bayer Ag | Phenylsulfonamid substituierte pyridinalken- und -aminooxyalkancarbonsaeure-derivate |
| NZ241574A (en) * | 1991-02-22 | 1993-08-26 | Ishihara Sangyo Kaisha | Substituted phenyl derivatives of hydrazone and pesticidal compositions |
| US5202327A (en) * | 1991-07-10 | 1993-04-13 | E. R. Squibb & Sons, Inc. | Phosphorus-containing hmg-coa reductase inhibitors |
| US5256692A (en) * | 1992-01-07 | 1993-10-26 | E. R. Squibb & Sons, Inc. | Sulfur-containing HMG-COA reductase inhibitors |
| US20010006644A1 (en) | 1997-07-31 | 2001-07-05 | David J. Bova | Combinations of hmg-coa reductase inhibitors and nicotinic acid and methods for treating hyperlipidemia once a day at night |
| WO2003076409A1 (en) * | 2002-03-14 | 2003-09-18 | Syngenta Participations Ag | Derivatives of 1-phenyl-3-phenylpyrazole as herbicides |
| JP4407237B2 (ja) * | 2002-12-24 | 2010-02-03 | 三菱化学株式会社 | 非水系電解液及びそれを用いる非水系電解液二次電池 |
| JP4485169B2 (ja) | 2003-05-16 | 2010-06-16 | 花王株式会社 | 腸管ミネラル吸収能改善剤 |
| CN1760363B (zh) * | 2004-10-14 | 2010-04-28 | 蒋继宏 | 杜仲3-羟基-3-甲基戊二酰辅酶a还原酶蛋白编码序列 |
| TW200736225A (en) * | 2006-01-16 | 2007-10-01 | Sankyo Agro Co Ltd | A (3-sulfur substituted phenyl) pyrazole derivative |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR339233A (fr) * | 1903-12-23 | 1905-01-26 | Cyanidgesellschaft Mit Beschra | Nouveau procédé pour l'obtention d'explosifs |
| DE803645C (de) * | 1949-10-11 | 1951-04-05 | Dynamit Act Ges Vormals Alfred | Schagwettersichere Sprengkapsel in Verbindung mit elektrischen Zuendern |
| DE918196C (de) * | 1952-12-23 | 1954-09-20 | J G W Berckholtz Fa | Masse zur Erzeugung von farbigem Rauch |
| US3274035A (en) * | 1964-06-15 | 1966-09-20 | Lohr A Burkardt | Metallic composition for production of hygroscopic smoke |
| US3862866A (en) * | 1971-08-02 | 1975-01-28 | Specialty Products Dev Corp | Gas generator composition and method |
| DE2841815C2 (de) * | 1978-09-26 | 1985-02-21 | Buck Chemisch-Technische Werke GmbH & Co, 7347 Bad Überkingen | Verfahren zur Herstellung einer Geschoßfüllung |
| US4438700A (en) * | 1982-07-19 | 1984-03-27 | The United States Of America As Represented By The Secretary Of The Army | White smoke spotting composition for training ammunition |
| FR2596393B1 (fr) * | 1986-04-01 | 1988-06-03 | Sanofi Sa | Derives de l'acide hydroxy-3 dihydroxyoxophosphorio-4 butanoique, leur procede de preparation, leur application comme medicament et les compositions les renfermant |
| NO882218L (no) * | 1987-05-22 | 1988-11-23 | Squibb & Sons Inc | Fremgangsmaate for fremstilling av fosforholdige hmg-coa reduktase-inhibitorer. |
-
1988
- 1988-05-20 PT PT87540A patent/PT87540B/pt not_active IP Right Cessation
- 1988-05-20 NO NO882219A patent/NO882219L/no unknown
- 1988-05-20 GB GB8811931A patent/GB2205838B/en not_active Expired - Fee Related
- 1988-05-20 SE SE8801904A patent/SE501541C2/sv not_active IP Right Cessation
- 1988-05-20 IT IT20681/88A patent/IT1217684B/it active
- 1988-05-20 HU HU882613A patent/HU201085B/hu not_active IP Right Cessation
- 1988-05-20 ES ES8801611A patent/ES2009919A6/es not_active Expired
- 1988-05-20 IL IL8646388A patent/IL86463A/en not_active IP Right Cessation
- 1988-05-20 DE DE3817298A patent/DE3817298C2/de not_active Expired - Fee Related
- 1988-05-20 FI FI882385A patent/FI87927C/fi not_active IP Right Cessation
- 1988-05-20 GR GR880100332A patent/GR880100332A/el unknown
- 1988-05-20 AU AU16502/88A patent/AU610174B2/en not_active Ceased
- 1988-05-20 IE IE154488A patent/IE63715B1/en not_active IP Right Cessation
- 1988-05-20 NZ NZ224734A patent/NZ224734A/en unknown
- 1988-05-20 DK DK277388A patent/DK277388A/da not_active Application Discontinuation
- 1988-05-20 PH PH36953A patent/PH25581A/en unknown
- 1988-05-21 PL PL1988286491A patent/PL157761B1/pl unknown
- 1988-05-21 CN CN88103699A patent/CN1030761A/zh active Pending
- 1988-05-21 KR KR1019880006019A patent/KR880013959A/ko not_active Application Discontinuation
- 1988-05-23 JP JP63125630A patent/JPH01139589A/ja active Pending
- 1988-05-24 CH CH1463/90A patent/CH678626A5/fr not_active IP Right Cessation
- 1988-05-24 BE BE8800565A patent/BE1002251A3/fr not_active IP Right Cessation
- 1988-05-24 CH CH1966/88A patent/CH675582A5/fr not_active IP Right Cessation
- 1988-05-24 NL NL8801331A patent/NL8801331A/nl not_active Application Discontinuation
- 1988-05-24 CH CH1462/90A patent/CH678625A5/fr not_active IP Right Cessation
- 1988-05-24 FR FR888806884A patent/FR2615516B1/fr not_active Expired - Fee Related
-
1989
- 1989-05-19 PH PH38673A patent/PH26578A/en unknown
-
1991
- 1991-02-21 AU AU71266/91A patent/AU643501B2/en not_active Ceased
-
1992
- 1992-05-14 SE SE9201587A patent/SE9201587D0/xx not_active Application Discontinuation
- 1992-05-20 SE SE9201588A patent/SE9201588D0/xx not_active Application Discontinuation
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