IE63715B1 - Phosphorus-containing hmg-coa reductase inhibitors - Google Patents
Phosphorus-containing hmg-coa reductase inhibitorsInfo
- Publication number
- IE63715B1 IE63715B1 IE154488A IE154488A IE63715B1 IE 63715 B1 IE63715 B1 IE 63715B1 IE 154488 A IE154488 A IE 154488A IE 154488 A IE154488 A IE 154488A IE 63715 B1 IE63715 B1 IE 63715B1
- Authority
- IE
- Ireland
- Prior art keywords
- fluorophenyl
- hydroxyphosphinyl
- phenyl
- methyl ester
- acid
- Prior art date
Links
- 229910052698 phosphorus Inorganic materials 0.000 title description 8
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 title description 5
- 239000011574 phosphorus Substances 0.000 title description 5
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 title description 3
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 title description 3
- 229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 title description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 143
- 150000001875 compounds Chemical class 0.000 claims abstract description 138
- 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 abstract description 48
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 44
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 27
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 24
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims description 208
- -1 t-butoxy Chemical group 0.000 claims description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 79
- SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 claims description 76
- 239000001257 hydrogen Substances 0.000 claims description 71
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 66
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 54
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 49
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 47
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 44
- 150000002431 hydrogen Chemical group 0.000 claims description 40
- 239000002253 acid Substances 0.000 claims description 37
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 35
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 35
- 235000010290 biphenyl Nutrition 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 150000002148 esters Chemical class 0.000 claims description 28
- 150000004702 methyl esters Chemical class 0.000 claims description 27
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000001153 fluoro group Chemical group F* 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 17
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 claims description 16
- 239000004305 biphenyl Substances 0.000 claims description 16
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 102000004190 Enzymes Human genes 0.000 claims description 11
- 108090000790 Enzymes Proteins 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 125000001589 carboacyl group Chemical group 0.000 claims description 8
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 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 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 claims description 4
- 125000005059 halophenyl group Chemical group 0.000 claims description 4
- 230000000055 hyoplipidemic effect Effects 0.000 claims description 4
- 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 description 3
- FGRBYDKOBBBPOI-UHFFFAOYSA-N 10,10-dioxo-2-[4-(N-phenylanilino)phenyl]thioxanthen-9-one Chemical compound O=C1c2ccccc2S(=O)(=O)c2ccc(cc12)-c1ccc(cc1)N(c1ccccc1)c1ccccc1 FGRBYDKOBBBPOI-UHFFFAOYSA-N 0.000 claims description 3
- 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 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- IJJBMJBRFVKIFA-FQEVSTJZSA-N (3s)-4-[2-[5-(4-fluorophenyl)-1-phenyl-3-propan-2-ylpyrazol-4-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)CCC=1C(C(C)C)=NN(C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 IJJBMJBRFVKIFA-FQEVSTJZSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- CJQHFCXDDTYBKR-BUHFOSPRSA-N 4-[[(e)-2-[5-(4-fluorophenyl)-1-phenyl-3-propan-2-ylpyrazol-4-yl]ethenyl]-methoxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)CC(O)CP(=O)(OC)\C=C\C=1C(C(C)C)=NN(C=2C=CC=CC=2)C=1C1=CC=C(F)C=C1 CJQHFCXDDTYBKR-BUHFOSPRSA-N 0.000 claims description 2
- LDLDJEAVRNAEBW-UHFFFAOYSA-N Methyl 3-hydroxybutyrate Chemical compound COC(=O)CC(C)O LDLDJEAVRNAEBW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000000871 hypocholesterolemic effect Effects 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims 4
- 125000003003 spiro group Chemical group 0.000 claims 2
- LFEDABOBESROQE-IBGZPJMESA-N (3s)-4-[2-[1-(4-fluorophenyl)-3-methylnaphthalen-2-yl]ethyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound OC(=O)C[C@H](O)CP(O)(=O)CCC=1C(C)=CC2=CC=CC=C2C=1C1=CC=C(F)C=C1 LFEDABOBESROQE-IBGZPJMESA-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
- AAQMQVNMIKIIFW-KRWDZBQOSA-N (3s)-4-[2-[2-(4-fluoro-3-methylphenyl)-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(C=2C=C(C)C(F)=CC=2)=C1 AAQMQVNMIKIIFW-KRWDZBQOSA-N 0.000 claims 1
- BFNYLDNOIRYKGM-KRWDZBQOSA-N (3s)-4-[2-[2-(4-fluoro-3-methylphenyl)-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(C=2C=C(C)C(F)=CC=2)=C1 BFNYLDNOIRYKGM-KRWDZBQOSA-N 0.000 claims 1
- SEFTYYXPKYYLBS-KRWDZBQOSA-N (3s)-4-[2-[2-(4-fluorophenyl)-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(C=2C=CC(F)=CC=2)=C1 SEFTYYXPKYYLBS-KRWDZBQOSA-N 0.000 claims 1
- VSYPBWUUYVLTPL-IBGZPJMESA-N (3s)-4-[2-[2-(cyclohexylmethyl)-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(CC2CCCCC2)=C1 VSYPBWUUYVLTPL-IBGZPJMESA-N 0.000 claims 1
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- PPWOSNFLPPZUDM-UHFFFAOYSA-N 4-[3-[2-(4-fluoro-3-methylphenyl)-4,6-dimethylphenyl]propyl-hydroxyphosphoryl]-3-hydroxybutanoic acid Chemical compound CC1=CC(C)=C(CCCP(O)(=O)CC(O)CC(O)=O)C(C=2C=C(C)C(F)=CC=2)=C1 PPWOSNFLPPZUDM-UHFFFAOYSA-N 0.000 claims 1
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- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 150000003573 thiols Chemical group 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
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- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
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Classifications
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- 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
-
- 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
-
- 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
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- 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
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- 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
- 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)]
- C07F9/306—Arylalkanephosphinic acids, e.g. Ar-(CH2)n-P(=X)(R)(XH), (X = O,S, Se; n>=1)
-
- 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)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3211—Esters of 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)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3217—Esters of 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)]
- C07F9/32—Esters thereof
- C07F9/3205—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/3241—Esters of arylalkanephosphinic 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
-
- 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
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
-
- 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
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2
-
- 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
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/6506—Five-membered rings having the nitrogen atoms in positions 1 and 3
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IE930369A IE63403B1 (en) | 1987-05-22 | 1993-05-20 | Phosphorus-containing hmg-coa reductase inhibitors new intermediates and method |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US5323887A | 1987-05-22 | 1987-05-22 | |
US10968187A | 1987-10-19 | 1987-10-19 |
Publications (2)
Publication Number | Publication Date |
---|---|
IE881544L IE881544L (en) | 1988-11-22 |
IE63715B1 true IE63715B1 (en) | 1995-06-14 |
Family
ID=26731613
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE154488A IE63715B1 (en) | 1987-05-22 | 1988-05-20 | Phosphorus-containing hmg-coa reductase inhibitors |
Country Status (24)
Country | Link |
---|---|
JP (1) | JPH01139589A (es) |
KR (1) | KR880013959A (es) |
CN (1) | CN1030761A (es) |
AU (2) | AU610174B2 (es) |
BE (1) | BE1002251A3 (es) |
CH (3) | CH675582A5 (es) |
DE (1) | DE3817298C2 (es) |
DK (1) | DK277388A (es) |
ES (1) | ES2009919A6 (es) |
FI (1) | FI87927C (es) |
FR (1) | FR2615516B1 (es) |
GB (1) | GB2205838B (es) |
GR (1) | GR880100332A (es) |
HU (1) | HU201085B (es) |
IE (1) | IE63715B1 (es) |
IL (1) | IL86463A (es) |
IT (1) | IT1217684B (es) |
NL (1) | NL8801331A (es) |
NO (1) | NO882219L (es) |
NZ (1) | NZ224734A (es) |
PH (2) | PH25581A (es) |
PL (1) | PL157761B1 (es) |
PT (1) | PT87540B (es) |
SE (3) | SE501541C2 (es) |
Families Citing this family (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3817375C2 (de) * | 1987-05-22 | 1997-04-30 | Squibb & Sons Inc | Phosphorhaltige HMG-CoA-Reduktase-Inhibitoren und ihre Verwendung |
IE903606A1 (en) * | 1989-10-10 | 1991-04-24 | Glaxo Group Ltd | Chemical compounds |
US5025000A (en) * | 1990-03-02 | 1991-06-18 | E. R. Squibb & Sons, Inc. | Phosphorus-containing HMG-CoA reductase inhibitor compounds |
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 |
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 |
DE3817375C2 (de) * | 1987-05-22 | 1997-04-30 | Squibb & Sons Inc | Phosphorhaltige HMG-CoA-Reduktase-Inhibitoren und ihre Verwendung |
-
1988
- 1988-05-20 AU AU16502/88A patent/AU610174B2/en not_active Ceased
- 1988-05-20 ES ES8801611A patent/ES2009919A6/es not_active Expired
- 1988-05-20 DE DE3817298A patent/DE3817298C2/de not_active Expired - Fee Related
- 1988-05-20 IE IE154488A patent/IE63715B1/en not_active IP Right Cessation
- 1988-05-20 FI FI882385A patent/FI87927C/fi not_active IP Right Cessation
- 1988-05-20 GB GB8811931A patent/GB2205838B/en not_active Expired - Fee Related
- 1988-05-20 NO NO882219A patent/NO882219L/no unknown
- 1988-05-20 DK DK277388A patent/DK277388A/da not_active Application Discontinuation
- 1988-05-20 PT PT87540A patent/PT87540B/pt 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 PH PH36953A patent/PH25581A/en unknown
- 1988-05-20 NZ NZ224734A patent/NZ224734A/en unknown
- 1988-05-20 IL IL8646388A patent/IL86463A/en not_active IP Right Cessation
- 1988-05-20 GR GR880100332A patent/GR880100332A/el unknown
- 1988-05-20 SE SE8801904A patent/SE501541C2/sv not_active IP Right Cessation
- 1988-05-21 KR KR1019880006019A patent/KR880013959A/ko not_active Application Discontinuation
- 1988-05-21 PL PL1988286491A patent/PL157761B1/pl unknown
- 1988-05-21 CN CN88103699A patent/CN1030761A/zh active Pending
- 1988-05-23 JP JP63125630A patent/JPH01139589A/ja active Pending
- 1988-05-24 FR FR888806884A patent/FR2615516B1/fr not_active Expired - Fee Related
- 1988-05-24 CH CH1966/88A patent/CH675582A5/fr not_active IP Right Cessation
- 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 NL NL8801331A patent/NL8801331A/nl not_active Application Discontinuation
- 1988-05-24 CH CH1462/90A patent/CH678625A5/fr not_active IP Right Cessation
-
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/SE9201588A0/sv not_active Application Discontinuation
Also Published As
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Legal Events
Date | Code | Title | Description |
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MM4A | Patent lapsed |