AU683552B2 - 4,6-DI-t-butyl-2,3-dihydrobenzothiophene derivative - Google Patents
4,6-DI-t-butyl-2,3-dihydrobenzothiophene derivative Download PDFInfo
- Publication number
- AU683552B2 AU683552B2 AU21485/95A AU2148595A AU683552B2 AU 683552 B2 AU683552 B2 AU 683552B2 AU 21485/95 A AU21485/95 A AU 21485/95A AU 2148595 A AU2148595 A AU 2148595A AU 683552 B2 AU683552 B2 AU 683552B2
- Authority
- AU
- Australia
- Prior art keywords
- optionally substituted
- butyl
- alkyl group
- hydrogen atom
- compound
- Prior art date
- Legal status (The legal status 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 status listed.)
- Ceased
Links
- NEVKGRDCAMPEII-UHFFFAOYSA-N 4,6-ditert-butyl-2,3-dihydro-1-benzothiophene Chemical class CC(C)(C)C1=CC(C(C)(C)C)=CC2=C1CCS2 NEVKGRDCAMPEII-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 99
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 24
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 23
- 125000005017 substituted alkenyl group Chemical group 0.000 claims abstract description 22
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 230000004048 modification Effects 0.000 claims abstract description 11
- 238000012986 modification Methods 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 206010003210 Arteriosclerosis Diseases 0.000 claims abstract description 9
- 208000011775 arteriosclerosis disease Diseases 0.000 claims abstract description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000001590 oxidative effect Effects 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 239000001301 oxygen Substances 0.000 claims abstract description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 8
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000002252 acyl group Chemical group 0.000 claims abstract description 7
- 239000003814 drug Substances 0.000 claims abstract description 7
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 6
- 125000003003 spiro group Chemical group 0.000 claims abstract description 5
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 4
- 239000011593 sulfur Substances 0.000 claims abstract description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 14
- 239000003085 diluting agent Substances 0.000 claims 4
- 239000003937 drug carrier Substances 0.000 claims 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 101100370100 Mus musculus Tor3a gene Proteins 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 208000001901 epithelial recurrent erosion dystrophy Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 165
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 50
- 230000015572 biosynthetic process Effects 0.000 description 50
- 238000003786 synthesis reaction Methods 0.000 description 48
- 239000007864 aqueous solution Substances 0.000 description 45
- 239000000203 mixture Substances 0.000 description 45
- -1 tbutyl Chemical group 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 38
- 239000011541 reaction mixture Substances 0.000 description 35
- 239000012141 concentrate Substances 0.000 description 33
- 238000010898 silica gel chromatography Methods 0.000 description 32
- 238000005481 NMR spectroscopy Methods 0.000 description 30
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 239000012044 organic layer Substances 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- 238000010992 reflux Methods 0.000 description 25
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
- 108010007622 LDL Lipoproteins Proteins 0.000 description 22
- 102000007330 LDL Lipoproteins Human genes 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
- 238000001816 cooling Methods 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- 239000012299 nitrogen atmosphere Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 238000003756 stirring Methods 0.000 description 18
- 239000012230 colorless oil Substances 0.000 description 16
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 230000003859 lipid peroxidation Effects 0.000 description 14
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- 239000000524 Thiobarbituric Acid Reactive Substance Substances 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 239000012280 lithium aluminium hydride Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 239000003963 antioxidant agent Substances 0.000 description 7
- 230000003078 antioxidant effect Effects 0.000 description 7
- 235000006708 antioxidants Nutrition 0.000 description 7
- ZXSBDSGRQIWJPM-UHFFFAOYSA-N dimethylcarbamothioic s-acid Chemical compound CN(C)C(S)=O ZXSBDSGRQIWJPM-UHFFFAOYSA-N 0.000 description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- LXEKPEMOWBOYRF-QDBORUFSSA-N AAPH Chemical compound Cl.Cl.NC(=N)C(C)(C)\N=N\C(C)(C)C(N)=N LXEKPEMOWBOYRF-QDBORUFSSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 6
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- MNGWKFNRROGUDS-UHFFFAOYSA-N [4,6-ditert-butyl-2-(iodomethyl)-2-methyl-3h-1-benzothiophen-5-yl] acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C2SC(C)(CI)CC2=C1C(C)(C)C MNGWKFNRROGUDS-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- OXTHDDIHJBDEEW-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dimethyl-3h-1-benzothiophen-5-ol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC2=C1CC(C)(C)S2 OXTHDDIHJBDEEW-UHFFFAOYSA-N 0.000 description 4
- HSBIASAJWXDTJM-UHFFFAOYSA-N 4,6-ditert-butyl-2,3-dihydro-1-benzothiophen-5-ol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC2=C1CCS2 HSBIASAJWXDTJM-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- OYHQOLUKZRVURQ-HZJYTTRNSA-N Linoleic acid Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(O)=O OYHQOLUKZRVURQ-HZJYTTRNSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 208000023589 ischemic disease Diseases 0.000 description 4
- OYHQOLUKZRVURQ-IXWMQOLASA-N linoleic acid Natural products CCCCC\C=C/C\C=C\CCCCCCCC(O)=O OYHQOLUKZRVURQ-IXWMQOLASA-N 0.000 description 4
- 235000020778 linoleic acid Nutrition 0.000 description 4
- CYAJEMFRSQGFIG-ISWIILBPSA-N microcystin-LA Natural products CO[C@@H](Cc1ccccc1)[C@@H](C)C=C(C)C=C[C@H](NC(=O)CNC(=O)[C@@H](C)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](C)NC(=O)C(=C)N(C)C(=O)CC[C@@H](C)C(=O)O)C(=O)O)[C@H](C)C(=O)N CYAJEMFRSQGFIG-ISWIILBPSA-N 0.000 description 4
- 208000010125 myocardial infarction Diseases 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 4
- SKKZEOWXZNQGGG-UHFFFAOYSA-N (2,6-ditert-butyl-4-hydroxyphenyl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C(O)C=C1C(C)(C)C SKKZEOWXZNQGGG-UHFFFAOYSA-N 0.000 description 3
- GTKGUPGJCXOVIH-UHFFFAOYSA-N (2,6-ditert-butyl-4-methoxyphenyl) acetate Chemical compound COC1=CC(C(C)(C)C)=C(OC(C)=O)C(C(C)(C)C)=C1 GTKGUPGJCXOVIH-UHFFFAOYSA-N 0.000 description 3
- MVMJPOWBEAVKQJ-UHFFFAOYSA-N (2,6-ditert-butyl-4-prop-2-enoxyphenyl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C(OCC=C)C=C1C(C)(C)C MVMJPOWBEAVKQJ-UHFFFAOYSA-N 0.000 description 3
- JYTUBGJBFNIIHP-UHFFFAOYSA-N (4,6-ditert-butyl-1,1-dioxo-2,3-dihydro-1-benzothiophen-5-yl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C2S(=O)(=O)CCC2=C1C(C)(C)C JYTUBGJBFNIIHP-UHFFFAOYSA-N 0.000 description 3
- YJUFGFXVASPYFQ-UHFFFAOYSA-N 2,3-dihydro-1-benzothiophene Chemical compound C1=CC=C2SCCC2=C1 YJUFGFXVASPYFQ-UHFFFAOYSA-N 0.000 description 3
- DCMQCQCKUAESOE-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dipentyl-3h-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(CCCCC)(CCCCC)C2 DCMQCQCKUAESOE-UHFFFAOYSA-N 0.000 description 3
- SDVQSQWWBOZKAK-UHFFFAOYSA-N 4,6-ditert-butyl-2-methyl-2,3-dihydro-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(C)C2 SDVQSQWWBOZKAK-UHFFFAOYSA-N 0.000 description 3
- VYGALKFTVWDPBT-UHFFFAOYSA-N 4h-1,2-benzoxazine Chemical compound C1=CC=C2CC=NOC2=C1 VYGALKFTVWDPBT-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 102000006991 Apolipoprotein B-100 Human genes 0.000 description 3
- 108010008150 Apolipoprotein B-100 Proteins 0.000 description 3
- 206010008190 Cerebrovascular accident Diseases 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 208000006011 Stroke Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- XZKXKIKWDQMOFZ-UHFFFAOYSA-N [2,6-ditert-butyl-3-[[(2-chloroacetyl)amino]methyl]-4-hydroxyphenyl] acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C(O)C(CNC(=O)CCl)=C1C(C)(C)C XZKXKIKWDQMOFZ-UHFFFAOYSA-N 0.000 description 3
- KMKKIKWBZRABCJ-UHFFFAOYSA-N [2,6-ditert-butyl-4-(2-methylprop-2-enoxy)phenyl] acetate Chemical compound CC(=C)COC1=CC(C(C)(C)C)=C(OC(C)=O)C(C(C)(C)C)=C1 KMKKIKWBZRABCJ-UHFFFAOYSA-N 0.000 description 3
- FYLWLHBPUCQEOQ-UHFFFAOYSA-N [2,6-ditert-butyl-4-(dimethylcarbamoylsulfanyl)-3-(2-methylprop-2-enyl)phenyl] acetate Chemical compound CN(C)C(=O)SC1=CC(C(C)(C)C)=C(OC(C)=O)C(C(C)(C)C)=C1CC(C)=C FYLWLHBPUCQEOQ-UHFFFAOYSA-N 0.000 description 3
- GMTYOINOBGLYGA-UHFFFAOYSA-N [2,6-ditert-butyl-4-(dimethylcarbamoylsulfanyl)-3-prop-2-enylphenyl] acetate Chemical compound CN(C)C(=O)SC1=CC(C(C)(C)C)=C(OC(C)=O)C(C(C)(C)C)=C1CC=C GMTYOINOBGLYGA-UHFFFAOYSA-N 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 238000006701 autoxidation reaction Methods 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- MXZACTZQSGYANA-UHFFFAOYSA-N chembl545463 Chemical compound Cl.C1=CC(OC)=CC=C1C(N=C1)=CN2C1=NC(C)=C2O MXZACTZQSGYANA-UHFFFAOYSA-N 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000004312 hexamethylene tetramine Substances 0.000 description 3
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- PHWISQNXPLXQRU-UHFFFAOYSA-N n,n-dimethylcarbamothioyl chloride Chemical compound CN(C)C(Cl)=S PHWISQNXPLXQRU-UHFFFAOYSA-N 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- ZXLSPBINTBCOEN-UHFFFAOYSA-N (2,6-ditert-butyl-3-formyl-4-hydroxyphenyl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C(O)C(C=O)=C1C(C)(C)C ZXLSPBINTBCOEN-UHFFFAOYSA-N 0.000 description 2
- XCRRGMKOURUQBY-UHFFFAOYSA-N (2,6-ditert-butyl-4-hydroxy-3-prop-2-enylphenyl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C(O)C(CC=C)=C1C(C)(C)C XCRRGMKOURUQBY-UHFFFAOYSA-N 0.000 description 2
- YOGQIUSKOWCRET-UHFFFAOYSA-N (4,6-ditert-butyl-1-benzothiophen-5-yl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C2SC=CC2=C1C(C)(C)C YOGQIUSKOWCRET-UHFFFAOYSA-N 0.000 description 2
- NSSXSQACWHFCOL-UHFFFAOYSA-N (4,6-ditert-butyl-2,2-dipentyl-3h-1-benzothiophen-5-yl) acetate Chemical compound C1=C(C(C)(C)C)C(OC(C)=O)=C(C(C)(C)C)C2=C1SC(CCCCC)(CCCCC)C2 NSSXSQACWHFCOL-UHFFFAOYSA-N 0.000 description 2
- XCSZBQMRQLIIDV-UHFFFAOYSA-N (5-acetyloxy-4,6-ditert-butyl-2-methyl-3h-1-benzothiophen-2-yl)methyl acetate Chemical compound C1=C(C(C)(C)C)C(OC(C)=O)=C(C(C)(C)C)C2=C1SC(COC(=O)C)(C)C2 XCSZBQMRQLIIDV-UHFFFAOYSA-N 0.000 description 2
- SXAMGRAIZSSWIH-UHFFFAOYSA-N 2-[3-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,2,4-oxadiazol-5-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NOC(=N1)CC(=O)N1CC2=C(CC1)NN=N2 SXAMGRAIZSSWIH-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- OHXAOPZTJOUYKM-UHFFFAOYSA-N 3-Chloro-2-methylpropene Chemical compound CC(=C)CCl OHXAOPZTJOUYKM-UHFFFAOYSA-N 0.000 description 2
- AGAVMBCDBACJEA-UHFFFAOYSA-N 4,6-ditert-butyl-1-benzothiophen-5-ol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC2=C1C=CS2 AGAVMBCDBACJEA-UHFFFAOYSA-N 0.000 description 2
- HYKLPZHCTSELKT-UHFFFAOYSA-N 4,6-ditert-butyl-2-(hydroxymethyl)-2-methyl-3h-1-benzothiophen-5-ol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC2=C1CC(C)(CO)S2 HYKLPZHCTSELKT-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229940123973 Oxygen scavenger Drugs 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 208000026062 Tissue disease Diseases 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- SPKKOVBESTYAOL-UHFFFAOYSA-N [2,6-ditert-butyl-4-hydroxy-3-(2-methylprop-2-enyl)phenyl] acetate Chemical compound CC(=C)CC1=C(O)C=C(C(C)(C)C)C(OC(C)=O)=C1C(C)(C)C SPKKOVBESTYAOL-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 239000001273 butane Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 210000000497 foam cell Anatomy 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 239000012285 osmium tetroxide Substances 0.000 description 2
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 2
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229940097156 peroxyl Drugs 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- GDDAJHJRAKOILH-QFXXITGJSA-N (2e,5e)-octa-2,5-diene Chemical compound CC\C=C\C\C=C\C GDDAJHJRAKOILH-QFXXITGJSA-N 0.000 description 1
- UVOZXTWWUCUVCM-UHFFFAOYSA-N (4,6-ditert-butyl-1,1-dioxo-1-benzothiophen-5-yl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C2S(=O)(=O)C=CC2=C1C(C)(C)C UVOZXTWWUCUVCM-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- OHZAHWOAMVVGEL-UHFFFAOYSA-N 2,2'-bithiophene Chemical compound C1=CSC(C=2SC=CC=2)=C1 OHZAHWOAMVVGEL-UHFFFAOYSA-N 0.000 description 1
- FQTMCXYNWGBAAZ-UHFFFAOYSA-N 2,2-dibenzyl-4,6-ditert-butyl-3h-1-benzothiophen-5-ol Chemical compound C1C=2C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=2SC1(CC=1C=CC=CC=1)CC1=CC=CC=C1 FQTMCXYNWGBAAZ-UHFFFAOYSA-N 0.000 description 1
- XIRXEQSRDLQINI-UHFFFAOYSA-N 2,4,6-tritert-butyl-2,3-dihydro-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(C(C)(C)C)C2 XIRXEQSRDLQINI-UHFFFAOYSA-N 0.000 description 1
- TXNSZCSYBXHETP-UHFFFAOYSA-N 2-chloro-n-(hydroxymethyl)acetamide Chemical compound OCNC(=O)CCl TXNSZCSYBXHETP-UHFFFAOYSA-N 0.000 description 1
- DCTLHSAKWZFDEY-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-di(propan-2-yl)-3h-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(C(C)C)(C(C)C)C2 DCTLHSAKWZFDEY-UHFFFAOYSA-N 0.000 description 1
- KYFPDXHQRXDENM-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-diethyl-3h-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(CC)(CC)C2 KYFPDXHQRXDENM-UHFFFAOYSA-N 0.000 description 1
- DPIYHGWDMOIUOO-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-diheptyl-3h-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(CCCCCCC)(CCCCCCC)C2 DPIYHGWDMOIUOO-UHFFFAOYSA-N 0.000 description 1
- XDOHZYNCUFGVOL-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dihexyl-3h-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(CCCCCC)(CCCCCC)C2 XDOHZYNCUFGVOL-UHFFFAOYSA-N 0.000 description 1
- BTCGLOHKLQEHIE-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dimethyl-7-propyl-3h-1-benzothiophen-5-ol Chemical compound OC1=C(C(C)(C)C)C(CCC)=C2SC(C)(C)CC2=C1C(C)(C)C BTCGLOHKLQEHIE-UHFFFAOYSA-N 0.000 description 1
- CIAFNUUMRQEKFX-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dioctyl-3h-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(CCCCCCCC)(CCCCCCCC)C2 CIAFNUUMRQEKFX-UHFFFAOYSA-N 0.000 description 1
- ZBCRLMVURVQEHI-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-diphenyl-3h-1-benzothiophen-5-ol Chemical compound C1C=2C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=2SC1(C=1C=CC=CC=1)C1=CC=CC=C1 ZBCRLMVURVQEHI-UHFFFAOYSA-N 0.000 description 1
- GRXRCGQXWULWAT-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dipropyl-3h-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(CCC)(CCC)C2 GRXRCGQXWULWAT-UHFFFAOYSA-N 0.000 description 1
- GAZZNXAWOJRQNA-UHFFFAOYSA-N 4,6-ditert-butyl-2-octyl-2,3-dihydro-1-benzothiophen-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1SC(CCCCCCCC)C2 GAZZNXAWOJRQNA-UHFFFAOYSA-N 0.000 description 1
- LXAKVLBCNLKTKI-UHFFFAOYSA-N 6-bromoundecane Chemical compound CCCCCC(Br)CCCCC LXAKVLBCNLKTKI-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- ZWPWSXGBDMGKKS-ZDUSSCGKSA-N Cypridina luciferin Chemical class C1=CC=C2C(C=3NC(CCCNC(N)=N)=C4N=C(C(N4C=3)=O)[C@@H](C)CC)=CNC2=C1 ZWPWSXGBDMGKKS-ZDUSSCGKSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 1
- 206010056740 Genital discharge Diseases 0.000 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 102000000853 LDL receptors Human genes 0.000 description 1
- 108010001831 LDL receptors Proteins 0.000 description 1
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical class [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- KFRCOJPPJMJQGZ-UHFFFAOYSA-N [2,6-ditert-butyl-4-(dimethylcarbamothioyloxy)-3-(2-methylprop-2-enyl)phenyl] acetate Chemical compound CN(C)C(=S)OC1=CC(C(C)(C)C)=C(OC(C)=O)C(C(C)(C)C)=C1CC(C)=C KFRCOJPPJMJQGZ-UHFFFAOYSA-N 0.000 description 1
- PWPKMEQGSCQLQH-UHFFFAOYSA-N [2,6-ditert-butyl-4-(dimethylcarbamoylsulfanyl)-3-(2-pentylhept-1-enyl)phenyl] acetate Chemical compound CCCCCC(CCCCC)=CC1=C(SC(=O)N(C)C)C=C(C(C)(C)C)C(OC(C)=O)=C1C(C)(C)C PWPKMEQGSCQLQH-UHFFFAOYSA-N 0.000 description 1
- OCTPAXIWFQNGCA-UHFFFAOYSA-N [2,6-ditert-butyl-4-hydroxy-3-(1-hydroxy-2-pentylheptyl)phenyl] acetate Chemical compound CCCCCC(CCCCC)C(O)C1=C(O)C=C(C(C)(C)C)C(OC(C)=O)=C1C(C)(C)C OCTPAXIWFQNGCA-UHFFFAOYSA-N 0.000 description 1
- YHQNMGBYJBLIBR-UHFFFAOYSA-N [2,6-ditert-butyl-4-hydroxy-3-(2-pentylhept-1-enyl)phenyl] acetate Chemical compound CCCCCC(CCCCC)=CC1=C(O)C=C(C(C)(C)C)C(OC(C)=O)=C1C(C)(C)C YHQNMGBYJBLIBR-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005233 alkylalcohol group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 230000000923 atherogenic effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- QHIMEFKYTNKHCI-UHFFFAOYSA-N chembl1193972 Chemical compound C1=CC(OC)=CC=C1C(N=C1)=CN2C1=NC(C)=C2O QHIMEFKYTNKHCI-UHFFFAOYSA-N 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 239000004914 cyclooctane Substances 0.000 description 1
- 125000002704 decyl group Chemical group [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])* 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000005558 fluorometry Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 125000002350 geranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000007654 ischemic lesion Effects 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
- QYZFTMMPKCOTAN-UHFFFAOYSA-N n-[2-(2-hydroxyethylamino)ethyl]-2-[[1-[2-(2-hydroxyethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]diazenyl]-2-methylpropanamide Chemical compound OCCNCCNC(=O)C(C)(C)N=NC(C)(C)C(=O)NCCNCCO QYZFTMMPKCOTAN-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000001400 nonyl 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])[H] 0.000 description 1
- 125000002347 octyl 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])[H] 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 102000014452 scavenger receptors Human genes 0.000 description 1
- 108010078070 scavenger receptors Proteins 0.000 description 1
- 150000003335 secondary amines Chemical class 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
- 229910001023 sodium amalgam Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- ZLOBIZSLPMOPDW-UHFFFAOYSA-N thiophene 1,1-dioxide Chemical compound O=S1(=O)[C]=CC=C1 ZLOBIZSLPMOPDW-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C333/00—Derivatives of thiocarbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C333/02—Monothiocarbamic acids; Derivatives thereof
- C07C333/04—Monothiocarbamic acids; Derivatives thereof having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/56—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/58—Radicals substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU45244/97A AU697801B2 (en) | 1994-04-11 | 1997-11-18 | Precursers to 4-6,di-t-butyl-2,3-dihydrobenzothiophene derivatives |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP10736594 | 1994-04-11 | ||
| JP6-107365 | 1994-04-11 | ||
| PCT/JP1995/000706 WO1995027710A1 (fr) | 1994-04-11 | 1995-04-11 | DERIVE DE 4,6-DI-t-BUTYL-2,3-DIHIDROBENZOTHIOPHENE |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU45244/97A Division AU697801B2 (en) | 1994-04-11 | 1997-11-18 | Precursers to 4-6,di-t-butyl-2,3-dihydrobenzothiophene derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU2148595A AU2148595A (en) | 1995-10-30 |
| AU683552B2 true AU683552B2 (en) | 1997-11-13 |
Family
ID=14457243
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU21485/95A Ceased AU683552B2 (en) | 1994-04-11 | 1995-04-11 | 4,6-DI-t-butyl-2,3-dihydrobenzothiophene derivative |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US5789436A (en, 2012) |
| EP (1) | EP0791589B1 (en, 2012) |
| CN (1) | CN1073563C (en, 2012) |
| AT (1) | ATE214059T1 (en, 2012) |
| AU (1) | AU683552B2 (en, 2012) |
| DE (1) | DE69525763T2 (en, 2012) |
| ES (1) | ES2173182T3 (en, 2012) |
| WO (1) | WO1995027710A1 (en, 2012) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW565558B (en) | 1995-11-09 | 2003-12-11 | Chugai Pharmaceutical Co Ltd | Intimal thickening inhibitory agent |
| DE19548708A1 (de) * | 1995-12-23 | 1997-06-26 | Merck Patent Gmbh | Cyclische Sulfone |
| EP0950405A4 (en) * | 1996-06-26 | 2004-03-17 | Chugai Pharmaceutical Co Ltd | TREATMENT OF KIDNEY DISEASES AND PROTECTION OF THE ORGANS |
| US6156793A (en) * | 1997-05-08 | 2000-12-05 | Chugai Seiyaku Kabushiki Kaisha | Prophylactic/therapeutic agents for atherosclerosis |
| TW472051B (en) | 1997-05-23 | 2002-01-11 | Chugai Pharmaceutical Co Ltd | 2,3-dihydrobenzofuran derivatives |
| ES2174538T3 (es) * | 1997-11-28 | 2002-11-01 | Knoll Ag | Procedimiento para la obtencion de substancias exentas de disolventes, no cristalinas, biologicamente activas. |
| US6420391B1 (en) | 1998-04-01 | 2002-07-16 | Ono Pharmaceutical Co., Ltd. | Fused thiophone derivatives and drugs containing the same as the active ingredient |
| DE10038709A1 (de) * | 2000-08-09 | 2002-02-28 | Aventis Pharma Gmbh | Substituierte und unsubstituierte Benzooxathiazole sowie daraus abgeleitete Verbindungen |
| DE60223227T8 (de) * | 2001-02-22 | 2008-11-27 | Teijin Pharma Ltd. | Benzo[b]thiophenderivate und Verfahren zu deren Herstellung |
| RU2184732C1 (ru) * | 2001-04-26 | 2002-07-10 | Некоммерческое партнерство "АСГЛ-Исследовательские лаборатории" | 5,5-дизамещенные-2-метил-9,9-диоксо-9-тиабицикло[4.3.0]нонаны |
| CN1646118A (zh) * | 2002-03-29 | 2005-07-27 | 中外制药株式会社 | 预防或治疗呼吸系统疾病的药物组合物 |
| DE10260095A1 (de) * | 2002-12-19 | 2004-07-01 | Basell Polyolefine Gmbh | Verfahren zur Herstellung von heterocyclischen Ketonen |
| CN102391521B (zh) * | 2011-06-30 | 2013-08-21 | 北京林业大学 | 一种改性碱木质素及其制备方法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0150966A2 (en) * | 1984-01-26 | 1985-08-07 | FISONS plc | Benzopyran derivatives, compositions containing them and processes for their preparation |
| JPH02121975A (ja) * | 1988-10-28 | 1990-05-09 | Eisai Co Ltd | ２，３−ジヒドロベンゾフラン誘導体 |
| EP0533579B1 (fr) * | 1991-09-18 | 1996-12-04 | Adir Et Compagnie | Nouveaux dérivés de la trimétazidine, leur procédé de préparation et les compositions pharmaceutiques les contenant |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3530146A (en) * | 1968-07-01 | 1970-09-22 | American Cyanamid Co | Substituted benzothiophendione compounds |
| JPS505356A (en, 2012) * | 1973-05-30 | 1975-01-21 | ||
| GB1456323A (en) * | 1974-06-06 | 1976-11-24 | Labaz | Benzothiophenes process for preparing them and pharmaceutical compositions containing the same |
| US4001426A (en) * | 1974-10-17 | 1977-01-04 | Smithkline Corporation | Substituted benzofurans and benzothiophenes |
| US4224330A (en) * | 1979-09-13 | 1980-09-23 | Zoecon Corporation | Esters and thiolesters of benzothienyl acids |
| JPS5646879A (en) * | 1979-09-25 | 1981-04-28 | Takeda Chem Ind Ltd | Spiro compound, its preparation, and preventive and remedy for circulatory system disorder |
| US4436748A (en) * | 1980-10-20 | 1984-03-13 | Hoechst-Roussel Pharmaceuticals Inc. | Benzo[b]thiophenes |
| US4418068A (en) * | 1981-04-03 | 1983-11-29 | Eli Lilly And Company | Antiestrogenic and antiandrugenic benzothiophenes |
| US4521320A (en) * | 1983-10-21 | 1985-06-04 | Ciba Geigy Corporation | Thiocarbamate stabilizers |
| GB8402047D0 (en) * | 1984-01-26 | 1984-02-29 | Fisons Plc | Nitrogen heterocycles |
| GB8406906D0 (en) * | 1984-03-16 | 1984-04-18 | Akzo Nv | Benzo-thiazole and benzothiophene derivatives |
| GB8417559D0 (en) * | 1984-07-10 | 1984-08-15 | Pfizer Ltd | Anti-diarrhoeal agents |
| US5112852A (en) * | 1986-12-23 | 1992-05-12 | Merrell Dow Pharmaceuticals Inc. | Allenyl amines |
| ES2052059T3 (es) * | 1988-03-16 | 1994-07-01 | Ciba Geigy Ag | Procedimiento para la obtencion de tiocompuestos. |
| US4963580A (en) * | 1988-10-18 | 1990-10-16 | Merck & Co., Inc. | Substituted 5-hydroxy-2,3-dihydrobenzothiophenes as inhibitors of leukotriene biosynthesis |
| GB2224028A (en) * | 1988-10-18 | 1990-04-25 | Merck & Co Inc | Substituted 5-hydroxy-2,3-dihydrobenzothiophenes as inhibitors of leukotriene biosynthesis |
| DE4115184A1 (de) * | 1991-05-09 | 1992-11-12 | Bayer Ag | Benzothiophen-2-carboxamid-s,s-dioxide |
| DE4204969A1 (de) * | 1992-02-19 | 1993-08-26 | Basf Ag | Verfahren zur herstellung von benzo(b)thiophenen |
| EP0639573A1 (de) * | 1993-08-03 | 1995-02-22 | Hoechst Aktiengesellschaft | Benzokondensierte 5-Ringheterocyclen, Verfahren zu ihrer Herstellung, ihre Verwendung als Medikament, ihre Verwendung als Diagnostikum, sowie sie enthaltendes Medikament |
-
1995
- 1995-04-11 DE DE69525763T patent/DE69525763T2/de not_active Expired - Fee Related
- 1995-04-11 CN CN95193057A patent/CN1073563C/zh not_active Expired - Fee Related
- 1995-04-11 AT AT95914557T patent/ATE214059T1/de not_active IP Right Cessation
- 1995-04-11 WO PCT/JP1995/000706 patent/WO1995027710A1/ja active IP Right Grant
- 1995-04-11 ES ES95914557T patent/ES2173182T3/es not_active Expired - Lifetime
- 1995-04-11 EP EP95914557A patent/EP0791589B1/en not_active Expired - Lifetime
- 1995-04-11 US US08/727,652 patent/US5789436A/en not_active Expired - Fee Related
- 1995-04-11 AU AU21485/95A patent/AU683552B2/en not_active Ceased
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0150966A2 (en) * | 1984-01-26 | 1985-08-07 | FISONS plc | Benzopyran derivatives, compositions containing them and processes for their preparation |
| JPH02121975A (ja) * | 1988-10-28 | 1990-05-09 | Eisai Co Ltd | ２，３−ジヒドロベンゾフラン誘導体 |
| EP0533579B1 (fr) * | 1991-09-18 | 1996-12-04 | Adir Et Compagnie | Nouveaux dérivés de la trimétazidine, leur procédé de préparation et les compositions pharmaceutiques les contenant |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1995027710A1 (fr) | 1995-10-19 |
| EP0791589A1 (en) | 1997-08-27 |
| DE69525763D1 (de) | 2002-04-11 |
| DE69525763T2 (de) | 2002-10-02 |
| ATE214059T1 (de) | 2002-03-15 |
| CN1148386A (zh) | 1997-04-23 |
| EP0791589B1 (en) | 2002-03-06 |
| ES2173182T3 (es) | 2002-10-16 |
| AU2148595A (en) | 1995-10-30 |
| EP0791589A4 (en, 2012) | 1997-08-27 |
| US5789436A (en) | 1998-08-04 |
| CN1073563C (zh) | 2001-10-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU683552B2 (en) | 4,6-DI-t-butyl-2,3-dihydrobenzothiophene derivative | |
| US5643943A (en) | Systemic administration of esters and amides of antioxidants which may be used as antioxidant prodrug therapy for oxidative and inflammatory pathogenesis | |
| EP0665208B1 (en) | 4-ALKOXY-2,6-DI-t-BUTYLPHENOL DERIVATIVE | |
| US5607966A (en) | Esters and amides of non-steroidal anti-inflammatory carboxylic acids which may be used as anti-oxidants, 5-lipoxygenase inhibitors and non-steroidal anti-inflammatory prodrugs | |
| EP0536036B1 (en) | Cardioprotective tocopherol analogs | |
| AU620660B2 (en) | Cardioprotective tocopherol analogs | |
| NZ229626A (en) | Sulphonamides and pharmaceutical compositions | |
| FR2574794A1 (fr) | Analogues de prostaglandines tetrahydrothienyl-substitues a action cardiovasculaire | |
| JPH01213270A (ja) | 新規な３，５―ジヒドロキシカルボン酸およびその誘導体 | |
| JP3050733B2 (ja) | ４−アルコキシ−２，６−ジ−ｔ−ブチルフェノール誘導体 | |
| IL98454A (en) | Dericatives of 2-aminoalkyl-5-arylalkyl-1,3-dioxanes their preparation and pharmaceutical compositions containing them | |
| JPH02745A (ja) | 新規なＨＭＧ―ＣｏＡ還元酵素阻害剤 | |
| JP3848387B2 (ja) | ４，６−ジ−ｔ−ブチル−２，３−ジヒドロベンゾチオフェン誘導体 | |
| CA2187315C (en) | 4,6-di-t-butyl-2,3-dihydrobenzothiophene derivatives | |
| KR100221354B1 (ko) | 4,6-디-t-부틸-2,3-디히드로벤조티오펜 유도체 | |
| US5504107A (en) | Optically pure 4-alkenyl- or 4-alkanyl-2-hydroxytetronic acids and pharmaceutical use thereof | |
| NZ245501A (en) | Sulphonium tocopherol derivatives and pharmaceutical compositions | |
| CA1326675C (fr) | Derives trieniques de structure chromenique, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent | |
| EP0428094B1 (en) | Mevinic acid derivatives | |
| Prasad et al. | Synthetic studies related to compactin: use of tri-O-acetyl-D-glucal for preparation of chiral cyclohexenes | |
| EP0450559A1 (en) | 3-hydroxy derivates of mevinic acid | |
| US5286746A (en) | Sulfur-substituted mevinic acid derivatives | |
| US4086249A (en) | Tetramethyl chromanyl pentane amide | |
| HU189582B (en) | Process for preparing 7-/4-substituted cyclopent-2-en-1-on-2-yl/-hept-2-trans-enoates, 2-arylthio-alkane-dicarboxylic acids and furyl derivatives thereof | |
| Muir et al. | Thromboxane receptor active analogues based on the 6-oxabicyclo [3.2. 1] octane ring system |