IL98712A - 2,6-di-alkyl-4-silyl-phenols as antiatherosclerotic agents and pharmaceutical compositions containing them - Google Patents
2,6-di-alkyl-4-silyl-phenols as antiatherosclerotic agents and pharmaceutical compositions containing themInfo
- Publication number
- IL98712A IL98712A IL9871291A IL9871291A IL98712A IL 98712 A IL98712 A IL 98712A IL 9871291 A IL9871291 A IL 9871291A IL 9871291 A IL9871291 A IL 9871291A IL 98712 A IL98712 A IL 98712A
- Authority
- IL
- Israel
- Prior art keywords
- compound
- phenol
- methyl
- butyl
- trimethylsilyl
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 9
- 230000000879 anti-atherosclerotic effect Effects 0.000 title abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 69
- -1 hydroxy, methoxy, ethoxy Chemical group 0.000 claims description 29
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 27
- 201000001320 Atherosclerosis Diseases 0.000 claims description 19
- 150000002632 lipids Chemical class 0.000 claims description 11
- 238000005502 peroxidation Methods 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 239000003963 antioxidant agent Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 230000003078 antioxidant effect Effects 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 2
- DNPZHPJIWPFTJR-UHFFFAOYSA-N 2,6-diethyl-4-(2-trimethylsilylethyl)phenol Chemical compound CCC1=CC(CC[Si](C)(C)C)=CC(CC)=C1O DNPZHPJIWPFTJR-UHFFFAOYSA-N 0.000 claims 1
- FOUIEJKGMNUGFB-UHFFFAOYSA-N 2,6-dimethyl-4-(2-trimethylsilylethyl)phenol Chemical compound CC1=CC(CC[Si](C)(C)C)=CC(C)=C1O FOUIEJKGMNUGFB-UHFFFAOYSA-N 0.000 claims 1
- IUBHEDXJIKRDEP-UHFFFAOYSA-N 2,6-dimethyl-4-(trimethylsilylmethoxy)phenol Chemical compound CC1=CC(OC[Si](C)(C)C)=CC(C)=C1O IUBHEDXJIKRDEP-UHFFFAOYSA-N 0.000 claims 1
- NGTZZNPNEVFWQS-UHFFFAOYSA-N 2,6-ditert-butyl-4-(trimethylsilylmethyl)benzenethiol Chemical compound CC(C)(C)C1=CC(C[Si](C)(C)C)=CC(C(C)(C)C)=C1S NGTZZNPNEVFWQS-UHFFFAOYSA-N 0.000 claims 1
- RSQWMMKMGWHSKF-UHFFFAOYSA-N 2,6-ditert-butyl-4-[[dimethyl(phenyl)silyl]methyl]benzenethiol Chemical compound CC(C)(C)C1=C(S)C(C(C)(C)C)=CC(C[Si](C)(C)C=2C=CC=CC=2)=C1 RSQWMMKMGWHSKF-UHFFFAOYSA-N 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 abstract description 8
- 230000003859 lipid peroxidation Effects 0.000 abstract description 7
- 239000003112 inhibitor Substances 0.000 abstract description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 24
- 108010007622 LDL Lipoproteins Proteins 0.000 description 23
- 102000007330 LDL Lipoproteins Human genes 0.000 description 23
- 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 20
- 239000000203 mixture Substances 0.000 description 18
- 238000000034 method Methods 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 238000011282 treatment Methods 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 8
- 235000012000 cholesterol Nutrition 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 6
- 238000009825 accumulation Methods 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 108010010234 HDL Lipoproteins Proteins 0.000 description 5
- 102000015779 HDL Lipoproteins Human genes 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 235000006708 antioxidants Nutrition 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- OOCUOKHIVGWCTJ-UHFFFAOYSA-N chloromethyl(trimethyl)silane Chemical compound C[Si](C)(C)CCl OOCUOKHIVGWCTJ-UHFFFAOYSA-N 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000011777 magnesium Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- NFVMNXZFSKGLDR-UHFFFAOYSA-N 2,6-ditert-butyl-4-sulfanylphenol Chemical compound CC(C)(C)C1=CC(S)=CC(C(C)(C)C)=C1O NFVMNXZFSKGLDR-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 210000000497 foam cell Anatomy 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 3
- 238000008214 LDL Cholesterol Methods 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 230000003143 atherosclerotic effect Effects 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 229960004217 benzyl alcohol Drugs 0.000 description 3
- 239000002981 blocking agent Substances 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 208000029078 coronary artery disease Diseases 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 150000003254 radicals Chemical class 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 description 2
- SGWZVZZVXOJRAQ-UHFFFAOYSA-N 2,6-Dimethyl-1,4-benzenediol Chemical compound CC1=CC(O)=CC(C)=C1O SGWZVZZVXOJRAQ-UHFFFAOYSA-N 0.000 description 2
- UYGBSRJODQHNLQ-UHFFFAOYSA-N 4-hydroxy-3,5-dimethylbenzaldehyde Chemical compound CC1=CC(C=O)=CC(C)=C1O UYGBSRJODQHNLQ-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 238000003747 Grignard reaction Methods 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000006866 deterioration Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 2
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 2
- OMIVCRYZSXDGAB-UHFFFAOYSA-N 1,4-butanediyl Chemical group [CH2]CC[CH2] OMIVCRYZSXDGAB-UHFFFAOYSA-N 0.000 description 1
- OHVLMTFVQDZYHP-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CN1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O OHVLMTFVQDZYHP-UHFFFAOYSA-N 0.000 description 1
- KZEVSDGEBAJOTK-UHFFFAOYSA-N 1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-2-[5-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]ethanone Chemical compound N1N=NC=2CN(CCC=21)C(CC=1OC(=NN=1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)=O KZEVSDGEBAJOTK-UHFFFAOYSA-N 0.000 description 1
- NVYLFDUUMDONLK-UHFFFAOYSA-N 1-chloropropyl(trimethyl)silane Chemical compound CCC(Cl)[Si](C)(C)C NVYLFDUUMDONLK-UHFFFAOYSA-N 0.000 description 1
- UOCURYNPYZDSSG-UHFFFAOYSA-N 2,6-ditert-butyl-4-(triethylsilylmethyl)benzenethiol Chemical compound CC[Si](CC)(CC)CC1=CC(C(C)(C)C)=C(S)C(C(C)(C)C)=C1 UOCURYNPYZDSSG-UHFFFAOYSA-N 0.000 description 1
- LDXJRKWFNNFDSA-UHFFFAOYSA-N 2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]ethanone Chemical compound C1CN(CC2=NNN=C21)CC(=O)N3CCN(CC3)C4=CN=C(N=C4)NCC5=CC(=CC=C5)OC(F)(F)F LDXJRKWFNNFDSA-UHFFFAOYSA-N 0.000 description 1
- JQMFQLVAJGZSQS-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-N-(2-oxo-3H-1,3-benzoxazol-6-yl)acetamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)NC1=CC2=C(NC(O2)=O)C=C1 JQMFQLVAJGZSQS-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- RVBUGGBMJDPOST-UHFFFAOYSA-N 2-thiobarbituric acid Chemical compound O=C1CC(=O)NC(=S)N1 RVBUGGBMJDPOST-UHFFFAOYSA-N 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- PVQUEBMXSXCSSZ-UHFFFAOYSA-N 4-(bromomethyl)-2,6-diethylphenol Chemical compound CCC1=CC(CBr)=CC(CC)=C1O PVQUEBMXSXCSSZ-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
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- 238000006027 Birch reduction reaction Methods 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
- C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
- C09K15/32—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing two or more of boron, silicon, phosphorus, selenium, tellurium or a metal
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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
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- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Anti-Oxidant Or Stabilizer Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/548,052 US5155250A (en) | 1990-07-05 | 1990-07-05 | 2,6-di-alkyl-4-silyl-phenols as antiatheroscerotic agents |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL98712A0 IL98712A0 (en) | 1992-07-15 |
| IL98712A true IL98712A (en) | 1995-11-27 |
Family
ID=24187205
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9871291A IL98712A (en) | 1990-07-05 | 1991-07-02 | 2,6-di-alkyl-4-silyl-phenols as antiatherosclerotic agents and pharmaceutical compositions containing them |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US5155250A (de) |
| EP (1) | EP0464852B1 (de) |
| JP (1) | JP2963556B2 (de) |
| KR (1) | KR0186005B1 (de) |
| CN (1) | CN1029615C (de) |
| AT (1) | ATE135705T1 (de) |
| AU (1) | AU639576B2 (de) |
| CA (1) | CA2046051C (de) |
| DE (1) | DE69118028T2 (de) |
| DK (1) | DK0464852T3 (de) |
| ES (1) | ES2087180T3 (de) |
| FI (1) | FI101703B1 (de) |
| GR (1) | GR3019393T3 (de) |
| HU (1) | HU211074B (de) |
| IE (1) | IE912340A1 (de) |
| IL (1) | IL98712A (de) |
| NO (1) | NO180490C (de) |
| NZ (1) | NZ238808A (de) |
| PT (1) | PT98220B (de) |
| ZA (1) | ZA915074B (de) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ238807A (en) * | 1990-07-05 | 1994-03-25 | Merrell Dow Pharma | Bis[4-(2,6-dialkyl)phenol]silane derivatives and antiatherosclerotic compositions |
| US5304668A (en) * | 1990-07-05 | 1994-04-19 | Merrell Dow Pharmaceuticals | Bis-[4-(2,6-di-alkyl)phenolisilane derivatives as antiatherosclerotic agents |
| FR2707989B1 (fr) * | 1993-07-22 | 1995-10-13 | Pf Medicament | Nouveaux dérivés de benzylamines silylées, leurs sels, leurs procédés de fabrication et les compositions pharmaceutiques les renfermant. |
| US5677291A (en) * | 1993-12-10 | 1997-10-14 | Hoechst Marion Roussel, Inc. | Method of lowering serum cholesterol levels with 2,6-di-alkyl-4-silyl-phenols |
| DE69434720T2 (de) * | 1993-12-10 | 2007-05-16 | Aventis Inc. | Verwendung von 2,6-Dialkyl-4-Silyl-Phenol Derivaten zur Behandlung von Xanthom |
| WO1995016712A1 (en) * | 1993-12-15 | 1995-06-22 | Smithkline Beecham Corporation | Compounds and methods |
| FR2722198B1 (fr) * | 1994-07-08 | 1996-10-04 | Pf Medicament | 1derives de silylmethyl-anilines, le2fabrication, et leur utilisation co |
| US5608095A (en) * | 1996-04-30 | 1997-03-04 | Hoechst Marion Roussel, Inc. | Alkyl-4-silyl-phenols and esters thereof as antiatherosclerotic agents |
| US5795876A (en) * | 1996-04-30 | 1998-08-18 | Hoechst Marion Rousssel, Inc. | Method of inhibiting vascular cell adhesion molecule-1 and treating chronic inflammatory diseases with 2, 6-di-alkyl-4-silyl-phenols |
| CN1216921A (zh) * | 1996-04-30 | 1999-05-19 | 赫彻斯特马里恩鲁斯公司 | 用2,6－二烷基－4－甲硅烷基－苯酚诱导血管细胞粘着分子－1和治疗慢性炎症疾病的方法 |
| EP0900241B1 (de) * | 1996-05-20 | 2004-01-28 | Smithkline Beecham Corporation | Silyl-linker für die organische synthese in fester phase von arylgruppen enthaltenden molekülen |
| US6114572A (en) * | 1996-11-20 | 2000-09-05 | Hoechst Marion Roussel, Inc. | Substituted phenols and thiophenols useful as antioxidant agents |
| US6670398B2 (en) * | 1997-05-14 | 2003-12-30 | Atherogenics, Inc. | Compounds and methods for treating transplant rejection |
| CN1275596C (zh) * | 1997-05-14 | 2006-09-20 | 阿特罗吉尼克斯公司 | 普罗布考单酯在制备用于治疗心血管疾病和炎性疾病的药物中的应用 |
| BR9810311A (pt) * | 1997-06-24 | 2000-09-19 | Hoechst Marion Roussel Inc | Fenóis alquil-4-silil heterocìclicos e tiofenóis úteis como agentes antioxidantes |
| US6121463A (en) * | 1997-06-24 | 2000-09-19 | Hoechst Marion Roussel, Inc. | Alkyl-4-silylheterocyclic phenols and thiophenols useful as antioxidant agents |
| CA2295232A1 (en) * | 1997-06-25 | 1998-12-30 | Hoechst Marion Roussel, Inc. | 2,6-di-t-butyl-4-[ (dimethyl-4-methoxyphenylsilyl) -methyloxy]phenol and 2,6-di-t-butyl-4-[ (dimethyl-2-methoxy-phenylsilyl) -methyloxy]phenol |
| US6133467A (en) * | 1997-06-25 | 2000-10-17 | Hoechst Marion Roussel, Inc. | 2,6-di-t-butyl-4-[(dimethyl-4-methoxyphenylsilyl)-methyl-oxy]phenol and 2,6-di-t-butyl-4-[(dimethyl-2-methoxy-phenylsilyl)methyloxy]phenol |
| WO1999001118A2 (en) * | 1997-07-01 | 1999-01-14 | Atherogenics, Inc. | Antioxidant enhancement of therapy for hyperproliferative conditions |
| JP2002529740A (ja) * | 1998-11-09 | 2002-09-10 | アセロジエニクス・インコーポレイテツド | 血漿コレステロールレベルを低下させるための方法及び組成物 |
| US6887712B1 (en) | 1998-11-09 | 2005-05-03 | Atherogenics, Inc. | Methods and compositions to lower plasma cholesterol levels |
| JP4408982B2 (ja) * | 1999-03-31 | 2010-02-03 | 東レ・ダウコーニング株式会社 | フェノール基含有有機ケイ素化合物およびその製造方法 |
| WO2002040021A2 (en) | 2000-11-17 | 2002-05-23 | Idenix (Cayman) Limited | Methods for inhibiting the transmission of hiv using topically applied substituted 6-benzyl-4-oxopyrimidines |
| JP2005514344A (ja) * | 2001-10-25 | 2005-05-19 | アセロジエニクス・インコーポレイテツド | 移植拒絶治療のための化合物と方法 |
| AU2002352826B2 (en) * | 2001-11-09 | 2009-05-28 | Atherogenics, Inc. | Methods of reversing and preventing cardiovascular pathologies |
| IL162533A0 (en) * | 2001-12-19 | 2005-11-20 | Atherogenics Inc | Chalcone derivatives and their use to treat diseases |
| US6960683B2 (en) * | 2002-07-12 | 2005-11-01 | Atherogenics, Inc. | Salt forms of poorly soluble probucol esters and ethers |
| AU2003266165A1 (en) * | 2002-09-13 | 2004-04-30 | Hossein Dovlatabadi | Methods and compositons for the use of d-malic acid to decrease serum triglyceride, cholesterol, and lipoprotein levels |
| WO2004056727A2 (en) * | 2002-12-19 | 2004-07-08 | Atherogenics, Inc. | Process of making chalcone derivatives |
| CN101391972A (zh) * | 2003-01-13 | 2009-03-25 | 阿特罗吉尼克斯公司 | 制备普罗布考及其衍生物的酯和醚的方法 |
| US7173129B2 (en) * | 2003-06-06 | 2007-02-06 | Athero Genics, Inc. | Sulfonamide-substituted chalcone derivatives and their use to treat diseases |
| WO2005037251A1 (en) * | 2003-10-17 | 2005-04-28 | Amylin Pharmaceuticals, Inc. | Self-emulsifying drug delivery systems for hydrophobic therapeutic compounds |
| JP2007509054A (ja) * | 2003-10-17 | 2007-04-12 | アミリン・ファーマシューティカルズ，インコーポレイテッド | 血管健康を促進するシリルフェノール |
| WO2005037250A1 (en) * | 2003-10-17 | 2005-04-28 | Amylin Pharmaceuticals, Inc. | Self emulsifying drug delivery systems for hydrophobic therapeutic compounds |
| WO2005112914A2 (en) | 2004-04-20 | 2005-12-01 | Atherogenics, Inc. | Phenolic antioxidants for the treatment of disorders including arthritis, asthma and coronary artery disease |
| US20070260087A1 (en) | 2004-04-20 | 2007-11-08 | Atherogenics, Inc. | Process of Preparing Esters and Ethers of Probucol and Derivatives Thereof |
| US20060063828A1 (en) * | 2004-06-28 | 2006-03-23 | Weingarten M D | 1,2-Bis-(substituted-phenyl)-2-propen-1-ones and pharmaceutical compositions thereof |
| EP1768660A4 (de) * | 2004-07-01 | 2009-05-13 | Atherogenics Inc | Verbindungen und verfahren zur behandlung von diabetischen gefässerkrankungen |
| EP2139320A4 (de) * | 2007-03-26 | 2010-09-08 | Salutria Pharmaceuticals Llc | Verfahren und zusammensetzungen von probucol-derivaten für die behandlung von diabetes |
| WO2008118946A1 (en) * | 2007-03-27 | 2008-10-02 | Atherogenics, Inc. | Methods and compositions using certain phenolic derivatives for the treatment of diabetes |
| DE102007015948A1 (de) * | 2007-04-03 | 2008-10-09 | Bayer Materialscience Ag | Modifizierte Polycarbonate, Polyestercarbonate und Polyester mit verbessertem Dehnverhalten und Flammwidrigkeit |
| US20090254425A1 (en) * | 2008-04-02 | 2009-10-08 | Evan Horowitz | Wiki-type collective intelligence mechanism for implementing a url redirect |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3328450A (en) * | 1963-01-09 | 1967-06-27 | Dow Corning | Silylalkyl phenols |
| US3506674A (en) * | 1967-07-03 | 1970-04-14 | Gen Electric | Certain pyridyl thio ether silanes |
| GB1232394A (de) * | 1967-08-17 | 1971-05-19 | ||
| US3853776A (en) * | 1972-09-29 | 1974-12-10 | Monsanto Co | Low pour point fluids and blends containing same |
| US3801617A (en) * | 1973-07-24 | 1974-04-02 | Nasa | Thiophenyl ether disiloxanes and trisiloxanes useful as lubricant fluids |
| DE2933206A1 (de) * | 1978-08-18 | 1980-02-28 | Ciba Geigy Ag | Phenolhaltige silane und deren verwendung als schmiermittelzusaetze |
| US4624909A (en) * | 1984-04-27 | 1986-11-25 | Nec Corporation | Silicon-containing novolak resin and resist material and pattern forming method using same |
| JPS61263988A (ja) * | 1985-05-16 | 1986-11-21 | Shionogi & Co Ltd | シリル置換エ−テル類および殺虫・殺ダニ剤 |
| US4636573A (en) * | 1985-09-09 | 1987-01-13 | Pastor Stephen D | Hindered silicon ester stabilizers |
| DE3604781A1 (de) * | 1986-02-13 | 1987-08-27 | Schering Ag | Neue silane, verfahren zu ihrer herstellung und diese verbindungen enthaltende einsektizide mittel |
| US4804653A (en) * | 1986-05-02 | 1989-02-14 | Uniroyal Chemical Company, Inc. | Thiomethyl-substituted organosilane compounds and their use as pesticides |
| DE3638073A1 (de) * | 1986-11-07 | 1988-05-11 | Swf Auto Electric Gmbh | Vorrichtung, insbesondere hubwischeranlage fuer kraftfahrzeuge |
| US4783495A (en) * | 1987-11-20 | 1988-11-08 | Ciba-Geigy Corporation | (Hydroxyphenyl) silane stabilizers |
| US5138012A (en) * | 1988-07-29 | 1992-08-11 | General Electric Company | Silicone release coating compositions |
| DE4031001A1 (de) * | 1990-10-01 | 1992-04-02 | Hoechst Ag | Verfahren zur herstellung von 4-ethoxyphenyl-3-arylpropyl-(dimethyl)silanen |
-
1990
- 1990-07-05 US US07/548,052 patent/US5155250A/en not_active Expired - Lifetime
-
1991
- 1991-07-01 NZ NZ238808A patent/NZ238808A/en not_active IP Right Cessation
- 1991-07-01 ZA ZA915074A patent/ZA915074B/xx unknown
- 1991-07-02 CA CA002046051A patent/CA2046051C/en not_active Expired - Lifetime
- 1991-07-02 IL IL9871291A patent/IL98712A/en not_active IP Right Cessation
- 1991-07-03 KR KR1019910011224A patent/KR0186005B1/ko not_active Expired - Fee Related
- 1991-07-03 AU AU80116/91A patent/AU639576B2/en not_active Ceased
- 1991-07-04 FI FI913252A patent/FI101703B1/fi active
- 1991-07-04 CN CN91104475A patent/CN1029615C/zh not_active Expired - Fee Related
- 1991-07-04 NO NO912630A patent/NO180490C/no not_active IP Right Cessation
- 1991-07-04 HU HU912272A patent/HU211074B/hu not_active IP Right Cessation
- 1991-07-04 PT PT98220A patent/PT98220B/pt not_active IP Right Cessation
- 1991-07-04 IE IE234091A patent/IE912340A1/en not_active IP Right Cessation
- 1991-07-04 JP JP3189497A patent/JP2963556B2/ja not_active Expired - Fee Related
- 1991-07-05 EP EP91111252A patent/EP0464852B1/de not_active Expired - Lifetime
- 1991-07-05 DE DE69118028T patent/DE69118028T2/de not_active Expired - Fee Related
- 1991-07-05 AT AT91111252T patent/ATE135705T1/de not_active IP Right Cessation
- 1991-07-05 DK DK91111252.2T patent/DK0464852T3/da active
- 1991-07-05 ES ES91111252T patent/ES2087180T3/es not_active Expired - Lifetime
-
1994
- 1994-12-12 US US08/353,736 patent/US5532400A/en not_active Expired - Lifetime
-
1996
- 1996-03-21 GR GR960400588T patent/GR3019393T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2046051C (en) | 2,6-di-alkyl-4-silyl-phenols as antiatherosclerotic agents | |
| US5677291A (en) | Method of lowering serum cholesterol levels with 2,6-di-alkyl-4-silyl-phenols | |
| CA2177968C (en) | Method of lowering serum cholesterol levels with 2,6-di-alkyl-4-silyl-phenols | |
| EP0464844B1 (de) | Bis (4-(2,6-dialkyl)phenol)silan Derivate als antiatherosclerotische Mittel und als Antioxidantien | |
| US5304668A (en) | Bis-[4-(2,6-di-alkyl)phenolisilane derivatives as antiatherosclerotic agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| HC | Change of name of proprietor(s) | ||
| KB20 | Patent renewed for 20 years | ||
| EXP | Patent expired |