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 them

Info

Publication number: IL98712A
Authority: IL; Israel
Prior art keywords: compound; phenol; methyl; butyl; trimethylsilyl
Prior art date: 1990-07-05

Application number

IL9871291A

Other languages

English (en)

Other versions

IL98712A0 (en

Original Assignee

Merrell Dow Pharma

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-07-05

Filing date

1991-07-02

Publication date

1995-11-27

1991-07-02 Application filed by Merrell Dow Pharma filed Critical Merrell Dow Pharma

1992-07-15 Publication of IL98712A0 publication Critical patent/IL98712A0/xx

1995-11-27 Publication of IL98712A publication Critical patent/IL98712A/en

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
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 1
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
238000006027 Birch reduction reaction Methods 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
DJEKAGRTVYNCKD-UHFFFAOYSA-N C(C)(C)(C)C1=C(C(=CC(=C1)CC[Si](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)O.C(C)(C)(C)C1=C(C(=CC(=C1)CC[Si](C1=CC=CC=C1)(C)C)C(C)(C)C)O.C(C)(C)(C)C1=C(C(=CC(=C1)CC[Si](C)(C)C)C(C)(C)C)O Chemical compound C(C)(C)(C)C1=C(C(=CC(=C1)CC[Si](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)O.C(C)(C)(C)C1=C(C(=CC(=C1)CC[Si](C1=CC=CC=C1)(C)C)C(C)(C)C)O.C(C)(C)(C)C1=C(C(=CC(=C1)CC[Si](C)(C)C)C(C)(C)C)O DJEKAGRTVYNCKD-UHFFFAOYSA-N 0.000 description 1
ZPNCUAPZYGWOCV-UHFFFAOYSA-N C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C(C)(C)C)C(C)(C)C)C(C)(C)C)S.C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)S.C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(CC(C)C)CC(C)C)C(C)(C)C)S Chemical compound C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C(C)(C)C)C(C)(C)C)C(C)(C)C)S.C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)S.C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(CC(C)C)CC(C)C)C(C)(C)C)S ZPNCUAPZYGWOCV-UHFFFAOYSA-N 0.000 description 1
FYXOHQBIFWXYTF-UHFFFAOYSA-N C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C(C)C)C(C)C)C(C)(C)C)S.C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C(C)C)(C(C)C)C(C)C)C(C)(C)C)S.C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(CCC)CCC)C(C)(C)C)S Chemical compound C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C(C)C)C(C)C)C(C)(C)C)S.C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C(C)C)(C(C)C)C(C)C)C(C)(C)C)S.C(C)(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(CCC)CCC)C(C)(C)C)S FYXOHQBIFWXYTF-UHFFFAOYSA-N 0.000 description 1
FDKXRSOPAQTJEY-UHFFFAOYSA-N C(C)(C)(C)C1=C(C(=CC(=C1)OC[Si](C1=CC=CC=C1)(C)C)C(C)(C)C)O.C(C)(C)(C)C1=C(C(=CC(=C1)OC[Si](C)(C)C)C(C)(C)C)O.C(CCC)C1=C(C(=CC(=C1)OC[Si](C1=CC=CC=C1)(CC)CC)CCCC)O Chemical compound C(C)(C)(C)C1=C(C(=CC(=C1)OC[Si](C1=CC=CC=C1)(C)C)C(C)(C)C)O.C(C)(C)(C)C1=C(C(=CC(=C1)OC[Si](C)(C)C)C(C)(C)C)O.C(CCC)C1=C(C(=CC(=C1)OC[Si](C1=CC=CC=C1)(CC)CC)CCCC)O FDKXRSOPAQTJEY-UHFFFAOYSA-N 0.000 description 1
AWMOCJMCMXHYPB-UHFFFAOYSA-N C(C)(C)C1=C(C(=CC(=C1)CC[Si](C)(C)C)C(C)C)O.C(CC)C1=C(C(=CC(=C1)CC[Si](C1=CC=CC=C1)(C)C)CCC)O.C(CC)C1=C(C(=CC(=C1)CC[Si](C)(C)C)CCC)O Chemical compound C(C)(C)C1=C(C(=CC(=C1)CC[Si](C)(C)C)C(C)C)O.C(CC)C1=C(C(=CC(=C1)CC[Si](C1=CC=CC=C1)(C)C)CCC)O.C(CC)C1=C(C(=CC(=C1)CC[Si](C)(C)C)CCC)O AWMOCJMCMXHYPB-UHFFFAOYSA-N 0.000 description 1
XFYTZJPHEZUCKP-UHFFFAOYSA-N C(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C(C)(C)C)C(C)(C)C)CC)S.C(C)C1=C(C(=CC(=C1)C[Si](C(C)(C)C)(C(C)(C)C)C(C)(C)C)CC)S.C(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)CC)S Chemical compound C(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C(C)(C)C)C(C)(C)C)CC)S.C(C)C1=C(C(=CC(=C1)C[Si](C(C)(C)C)(C(C)(C)C)C(C)(C)C)CC)S.C(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)CC)S XFYTZJPHEZUCKP-UHFFFAOYSA-N 0.000 description 1
FQALSUWIFUKCAS-UHFFFAOYSA-N C(CC)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)CCC)S.C(CC)C1=C(C(=CC(=C1)C[Si](C)(C)C)CCC)S Chemical compound C(CC)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)CCC)S.C(CC)C1=C(C(=CC(=C1)C[Si](C)(C)C)CCC)S FQALSUWIFUKCAS-UHFFFAOYSA-N 0.000 description 1
BLDLSNBJQNXOPO-UHFFFAOYSA-N C(CCC)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)CCCC)S.C(CCC)C1=C(C(=CC(=C1)C[Si](C)(C)C)CCCC)S.C(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)C(C)C)S Chemical compound C(CCC)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)CCCC)S.C(CCC)C1=C(C(=CC(=C1)C[Si](C)(C)C)CCCC)S.C(C)(C)C1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)C(C)C)S BLDLSNBJQNXOPO-UHFFFAOYSA-N 0.000 description 1
SIHFBXIWVZBZKB-UHFFFAOYSA-N CC1=C(C(=CC(=C1)CC[Si](C1=CC=CC=C1)(C)C)C)O.CC1=C(C(=CC(=C1)CC[Si](C)(C)C)C)O.C(C)(C)(C)C1=C(C(=CC(=C1)CC[Si](C1=CC=CC=C1)(C(C)(C)C)C(C)(C)C)C(C)(C)C)O Chemical compound CC1=C(C(=CC(=C1)CC[Si](C1=CC=CC=C1)(C)C)C)O.CC1=C(C(=CC(=C1)CC[Si](C)(C)C)C)O.C(C)(C)(C)C1=C(C(=CC(=C1)CC[Si](C1=CC=CC=C1)(C(C)(C)C)C(C)(C)C)C(C)(C)C)O SIHFBXIWVZBZKB-UHFFFAOYSA-N 0.000 description 1
CNOKDVFILHVSIM-UHFFFAOYSA-N CC1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(CCCC)CCCC)C)S.CC1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)C)S.CC1=C(C(=CC(=C1)C[Si](C)(C)C)C)S Chemical compound CC1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(CCCC)CCCC)C)S.CC1=C(C(=CC(=C1)C[Si](C1=CC=CC=C1)(C)C)C)S.CC1=C(C(=CC(=C1)C[Si](C)(C)C)C)S CNOKDVFILHVSIM-UHFFFAOYSA-N 0.000 description 1
108010004103 Chylomicrons Proteins 0.000 description 1
229940126062 Compound A Drugs 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
206010061216 Infarction Diseases 0.000 description 1
108010028554 LDL Cholesterol Proteins 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
244000246386 Mentha pulegium Species 0.000 description 1
235000016257 Mentha pulegium Nutrition 0.000 description 1
235000004357 Mentha x piperita Nutrition 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
AFCARXCZXQIEQB-UHFFFAOYSA-N N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CCNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 AFCARXCZXQIEQB-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
241000283984 Rodentia Species 0.000 description 1
229920001800 Shellac Polymers 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
JARMUKWSAYQPKJ-UHFFFAOYSA-N [4-(bromomethyl)-2,6-dimethylphenyl] acetate Chemical compound CC(=O)OC1=C(C)C=C(CBr)C=C1C JARMUKWSAYQPKJ-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
239000003708 ampul Substances 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
150000005840 aryl radicals Chemical class 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000036765 blood level Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Chemical group 0.000 description 1
ACAUYCZBWABOLI-UHFFFAOYSA-N bromomethyl(trimethyl)silane Chemical compound C[Si](C)(C)CBr ACAUYCZBWABOLI-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
230000015556 catabolic process Effects 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
235000015218 chewing gum Nutrition 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
RJCTVFQQNCNBHG-UHFFFAOYSA-N chloromethyl-dimethyl-phenylsilane Chemical compound ClC[Si](C)(C)C1=CC=CC=C1 RJCTVFQQNCNBHG-UHFFFAOYSA-N 0.000 description 1
YUWMHVAIAHCLSE-UHFFFAOYSA-N chloromethyl-dodecyl-dimethylsilane Chemical compound CCCCCCCCCCCC[Si](C)(C)CCl YUWMHVAIAHCLSE-UHFFFAOYSA-N 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
238000004040 coloring Methods 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
229940124301 concurrent medication Drugs 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 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 description 1
230000006378 damage Effects 0.000 description 1
238000006731 degradation reaction Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
PIZLBWGMERQCOC-UHFFFAOYSA-N dibenzyl carbonate Chemical compound C=1C=CC=CC=1COC(=O)OCC1=CC=CC=C1 PIZLBWGMERQCOC-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000975 dye Substances 0.000 description 1
229960001484 edetic acid Drugs 0.000 description 1
230000000694 effects Effects 0.000 description 1
229920001971 elastomer Polymers 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
210000003038 endothelium Anatomy 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
239000003925 fat Substances 0.000 description 1
239000010685 fatty oil Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000011521 glass Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
208000019622 heart disease Diseases 0.000 description 1
235000001050 hortel pimenta Nutrition 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
239000003701 inert diluent Substances 0.000 description 1
230000007574 infarction Effects 0.000 description 1
208000014674 injury Diseases 0.000 description 1
VZNYXGQMDSRJAL-UHFFFAOYSA-N iodomethyl(trimethyl)silane Chemical compound C[Si](C)(C)CI VZNYXGQMDSRJAL-UHFFFAOYSA-N 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
230000029226 lipidation Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000011344 liquid material Substances 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
CXHHBNMLPJOKQD-UHFFFAOYSA-M methyl carbonate Chemical compound COC([O-])=O CXHHBNMLPJOKQD-UHFFFAOYSA-M 0.000 description 1
STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
229940012189 methyl orange Drugs 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960001047 methyl salicylate Drugs 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
208000031225 myocardial ischemia Diseases 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
239000000346 nonvolatile oil Substances 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
239000011368 organic material Substances 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000003209 petroleum derivative Substances 0.000 description 1
125000000286 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
235000021317 phosphate Nutrition 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
230000007505 plaque formation Effects 0.000 description 1
230000008569 process Effects 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
239000005060 rubber Substances 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000012056 semi-solid material Substances 0.000 description 1
239000004208 shellac Substances 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000004149 thio group Chemical group *S* 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
235000012431 wafers Nutrition 0.000 description 1
239000008215 water for injection Substances 0.000 description 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
- 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
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Materials Engineering (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Diabetes (AREA)
Endocrinology (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Compositions Of Macromolecular Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Anti-Oxidant Or Stabilizer Compositions (AREA)

IL9871291A 1990-07-05 1991-07-02 2,6-di-alkyl-4-silyl-phenols as antiatherosclerotic agents and pharmaceutical compositions containing them IL98712A (en)

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 (fi)
EP (1)	EP0464852B1 (fi)
JP (1)	JP2963556B2 (fi)
KR (1)	KR0186005B1 (fi)
CN (1)	CN1029615C (fi)
AT (1)	ATE135705T1 (fi)
AU (1)	AU639576B2 (fi)
CA (1)	CA2046051C (fi)
DE (1)	DE69118028T2 (fi)
DK (1)	DK0464852T3 (fi)
ES (1)	ES2087180T3 (fi)
FI (1)	FI101703B (fi)
GR (1)	GR3019393T3 (fi)
HU (1)	HU211074B (fi)
IE (1)	IE912340A1 (fi)
IL (1)	IL98712A (fi)
NO (1)	NO180490C (fi)
NZ (1)	NZ238808A (fi)
PT (1)	PT98220B (fi)
ZA (1)	ZA915074B (fi)

Families Citing this family (42)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5304668A (en) *	1990-07-05	1994-04-19	Merrell Dow Pharmaceuticals	Bis-[4-(2,6-di-alkyl)phenolisilane derivatives as antiatherosclerotic agents
NZ238807A (en) *	1990-07-05	1994-03-25	Merrell Dow Pharma	Bis[4-(2,6-dialkyl)phenol]silane derivatives and antiatherosclerotic compositions
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
DK0732928T3 (da) *	1993-12-10	2005-04-18	Merrell Pharma Inc	Fremgangsmåde til sænkning af serumcholesterolnuiveauer med 2,6-di-alkyl-4-silyl-phenoler
JPH09506913A (ja) *	1993-12-15	1997-07-08	スミスクライン・ビーチャム・コーポレイション	化合物および方法
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
EP0910384A1 (en) *	1996-04-30	1999-04-28	Hoechst Marion Roussel, Inc.	Method of inhibiting vascular cell adhesion molecule-1 and treating chronic inflammatory diseases with 2,6-di-alkyl-4-silyl-phenols
WO1997044367A1 (en) *	1996-05-20	1997-11-27	Smithkline Beecham Corporation	Silyl linker for solid phase organic synthesis of aryl-containing molecules
US6114572A (en) *	1996-11-20	2000-09-05	Hoechst Marion Roussel, Inc.	Substituted phenols and thiophenols useful as antioxidant agents
TR199902803T2 (xx) *	1997-05-14	2000-07-21	Atherogenics, Inc.	VCAM-1' in te�hisinin daralt�lmas� i�in bile�ikler ve metodlar.
US6670398B2 (en) *	1997-05-14	2003-12-30	Atherogenics, Inc.	Compounds and methods for treating transplant rejection
JP2002514226A (ja) *	1997-06-24	2002-05-14	アベンティス・ファーマスーティカルズ・インコーポレイテッド	抗酸化剤としてのアルキル−４−シリル複素環フェノール及びチオフェノール
US6121463A (en) *	1997-06-24	2000-09-19	Hoechst Marion Roussel, Inc.	Alkyl-4-silylheterocyclic phenols and thiophenols useful as antioxidant agents
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
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
KR20010020611A (ko) *	1997-07-01	2001-03-15	아테로제닉스, 인코포레이티드	항산화제에 의한 과증식질병 치료의 향상
US6887712B1 (en)	1998-11-09	2005-05-03	Atherogenics, Inc.	Methods and compositions to lower plasma cholesterol levels
EP1137948B1 (en) *	1998-11-09	2006-05-10	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
AU2002248910A1 (en)	2000-11-17	2002-05-27	Idenix (Cayman) Limited	Methods for inhibiting the transmission of HIV using topically applied substituted 6-benzyl-4-oxopyrmidines
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
AU2002360763A1 (en) *	2001-12-19	2003-07-09	Atherogenics, Inc.	Chalcone derivatives and their use to treat diseases
CA2492433A1 (en) *	2002-07-12	2004-01-22	Artherogenics, Inc.	Organic amine salts of poorly soluble probucol esters and ethers
US20040110803A1 (en) *	2002-09-13	2004-06-10	Hossein Dovlatabadi	Methods and compositions for the use of D-malic acid to decrease serum triglyceride, cholesterol and lipoprotein levels
AU2003303239A1 (en) *	2002-12-19	2004-07-14	Atherogenics, Inc.	Process of making chalcone derivatives
US7273948B2 (en) *	2003-01-13	2007-09-25	Atherogenics, Inc.	Process of preparing esters and ethers of probucol and derivatives thereof
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
EP1677804A1 (en) *	2003-10-17	2006-07-12	Amylin Pharmaceuticals, Inc.	Silyl phenols for promoting vascular health
WO2005037250A1 (en) *	2003-10-17	2005-04-28	Amylin Pharmaceuticals, Inc.	Self emulsifying drug delivery systems for hydrophobic therapeutic compounds
US7294737B2 (en)	2004-04-20	2007-11-13	Atherogenics, Inc.	Process of preparing esters and ethers of probucol and derivatives thereof
WO2005112914A2 (en)	2004-04-20	2005-12-01	Atherogenics, Inc.	Phenolic antioxidants for the treatment of disorders including arthritis, asthma and coronary artery disease
WO2006004903A2 (en) *	2004-06-28	2006-01-12	Atherogenics, Inc.	1,2-bis-(substituted-phenyl)-2-propen-1-ones and pharmaceutical compositions thereof
US20060058268A1 (en) *	2004-07-01	2006-03-16	Sundell Cynthia L	Compounds and methods for treating diabetic vascular diseases
CN101686676A (zh) *	2007-03-26	2010-03-31	沙路特里亚制药有限责任公司	用于治疗糖尿病的方法和普罗布考衍生物的组合物
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)

* Cited by examiner, † Cited by third party
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 (fi) *	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 ZA ZA915074A patent/ZA915074B/xx unknown
- 1991-07-01 NZ NZ238808A patent/NZ238808A/en not_active IP Right Cessation
- 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 PT PT98220A patent/PT98220B/pt not_active IP Right Cessation
- 1991-07-04 NO NO912630A patent/NO180490C/no not_active IP Right Cessation
- 1991-07-04 CN CN91104475A patent/CN1029615C/zh not_active Expired - Fee Related
- 1991-07-04 IE IE234091A patent/IE912340A1/en not_active IP Right Cessation
- 1991-07-04 FI FI913252A patent/FI101703B/fi active
- 1991-07-04 HU HU912272A patent/HU211074B/hu 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/en not_active Expired - Lifetime
- 1991-07-05 DE DE69118028T patent/DE69118028T2/de not_active Expired - Fee Related
- 1991-07-05 ES ES91111252T patent/ES2087180T3/es not_active Expired - Lifetime
- 1991-07-05 DK DK91111252.2T patent/DK0464852T3/da active
- 1991-07-05 AT AT91111252T patent/ATE135705T1/de not_active IP Right Cessation
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

Publication number	Publication date
JP2963556B2 (ja)	1999-10-18
US5532400A (en)	1996-07-02
AU8011691A (en)	1992-01-09
AU639576B2 (en)	1993-07-29
KR0186005B1 (ko)	1999-05-15
JPH04230393A (ja)	1992-08-19
KR920002617A (ko)	1992-02-28
ES2087180T3 (es)	1996-07-16
FI101703B1 (fi)	1998-08-14
NO912630D0 (no)	1991-07-04
EP0464852B1 (en)	1996-03-20
CN1057843A (zh)	1992-01-15
DE69118028T2 (de)	1996-11-28
FI913252L (fi)	1992-01-06
US5155250A (en)	1992-10-13
CA2046051A1 (en)	1992-01-06
ZA915074B (en)	1992-04-29
CA2046051C (en)	2001-06-05
PT98220B (pt)	1998-12-31
HUT58749A (en)	1992-03-30
GR3019393T3 (en)	1996-06-30
DK0464852T3 (da)	1996-04-15
NZ238808A (en)	1994-02-25
CN1029615C (zh)	1995-08-30
NO180490B (no)	1997-01-20
ATE135705T1 (de)	1996-04-15
DE69118028D1 (de)	1996-04-25
IE912340A1 (en)	1992-01-15
FI913252A0 (fi)	1991-07-04
PT98220A (pt)	1992-05-29
HU912272D0 (en)	1991-12-30
IL98712A0 (en)	1992-07-15
HU211074B (en)	1995-10-30
EP0464852A1 (en)	1992-01-08
FI101703B (fi)	1998-08-14
NO180490C (no)	1997-04-30
NO912630L (no)	1992-01-06

Publication	Publication Date	Title
CA2046051C (en)	2001-06-05	2,6-di-alkyl-4-silyl-phenols as antiatherosclerotic agents
US5677291A (en)	1997-10-14	Method of lowering serum cholesterol levels with 2,6-di-alkyl-4-silyl-phenols
CA2177968C (en)	2000-03-28	Method of lowering serum cholesterol levels with 2,6-di-alkyl-4-silyl-phenols
EP0464844B1 (en)	1995-12-27	Novel bis (4-(2,6-di-alkyl)phenol)silane derivatives as antiatherosclerotic agents and as antioxidants
US5304668A (en)	1994-04-19	Bis-[4-(2,6-di-alkyl)phenolisilane derivatives as antiatherosclerotic agents

Legal Events

Date	Code	Title
1996-05-14	FF	Patent granted
1998-01-04	KB	Patent renewed
1998-02-08	HC	Change of name of proprietor(s)
2001-07-24	KB20	Patent renewed for 20 years
2012-02-29	EXP	Patent expired