DE2858726C2 - Arzneimittel zur senkung des serumcholesterinspiegels - Google Patents
Arzneimittel zur senkung des serumcholesterinspiegelsInfo
- Publication number
- DE2858726C2 DE2858726C2 DE2858726A DE2858726A DE2858726C2 DE 2858726 C2 DE2858726 C2 DE 2858726C2 DE 2858726 A DE2858726 A DE 2858726A DE 2858726 A DE2858726 A DE 2858726A DE 2858726 C2 DE2858726 C2 DE 2858726C2
- Authority
- DE
- Germany
- Prior art keywords
- cholest
- ether
- analyzes
- ethyl
- benzene
- 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.)
- Expired - Fee Related
Links
- 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 title claims description 57
- 239000003814 drug Substances 0.000 title claims description 10
- 210000002966 serum Anatomy 0.000 title description 2
- HVYWMOMLDIMFJA-UHFFFAOYSA-N 3-cholesterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 HVYWMOMLDIMFJA-UHFFFAOYSA-N 0.000 title 1
- 229930182558 Sterol Natural products 0.000 claims description 46
- 235000003702 sterols Nutrition 0.000 claims description 46
- 150000003432 sterols Chemical class 0.000 claims description 44
- 239000004480 active ingredient Substances 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical class S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
- IVMZFFSMKDJDLO-NUNHNUFQSA-N (5s,9r,10s,13r,15s,17r)-14-ethyl-15-hydroxy-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,4,5,6,9,11,12,15,16,17-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@]4(C)[C@@H]([C@H](C)CCCC(C)C)C[C@H](O)C4(CC)C3=CC[C@H]21 IVMZFFSMKDJDLO-NUNHNUFQSA-N 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 239000012059 conventional drug carrier Substances 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 229910052700 potassium Chemical class 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 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 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 226
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 201
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 96
- 239000002904 solvent Substances 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 60
- 239000000203 mixture Substances 0.000 description 59
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- 150000001875 compounds Chemical class 0.000 description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 46
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- 239000000243 solution Substances 0.000 description 36
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 34
- 238000002360 preparation method Methods 0.000 description 33
- 239000007788 liquid Substances 0.000 description 31
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 29
- 238000001704 evaporation Methods 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- 229960001866 silicon dioxide Drugs 0.000 description 28
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 27
- 230000008020 evaporation Effects 0.000 description 27
- 238000004809 thin layer chromatography Methods 0.000 description 25
- 230000015572 biosynthetic process Effects 0.000 description 24
- 239000000047 product Substances 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 19
- 235000012000 cholesterol Nutrition 0.000 description 18
- -1 Acetate sterols Chemical class 0.000 description 17
- 239000000284 extract Substances 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000011780 sodium chloride Substances 0.000 description 14
- 241000700159 Rattus Species 0.000 description 13
- 239000012280 lithium aluminium hydride Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 10
- 150000002009 diols Chemical class 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000012259 ether extract Substances 0.000 description 10
- 150000004678 hydrides Chemical class 0.000 description 10
- KJTLQQUUPVSXIM-ZCFIWIBFSA-N (R)-mevalonic acid Chemical compound OCC[C@](O)(C)CC(O)=O KJTLQQUUPVSXIM-ZCFIWIBFSA-N 0.000 description 9
- KJTLQQUUPVSXIM-UHFFFAOYSA-N DL-mevalonic acid Natural products OCCC(O)(C)CC(O)=O KJTLQQUUPVSXIM-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical class C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000012746 preparative thin layer chromatography Methods 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 235000017550 sodium carbonate Nutrition 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
- BAECOWNUKCLBPZ-HIUWNOOHSA-N Triolein Natural products O([C@H](OCC(=O)CCCCCCC/C=C\CCCCCCCC)COC(=O)CCCCCCC/C=C\CCCCCCCC)C(=O)CCCCCCC/C=C\CCCCCCCC BAECOWNUKCLBPZ-HIUWNOOHSA-N 0.000 description 4
- PHYFQTYBJUILEZ-UHFFFAOYSA-N Trioleoylglycerol Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCCCCCCCC)COC(=O)CCCCCCCC=CCCCCCCCC PHYFQTYBJUILEZ-UHFFFAOYSA-N 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- PHYFQTYBJUILEZ-IUPFWZBJSA-N triolein Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CCCCCCCC)COC(=O)CCCCCCC\C=C/CCCCCCCC PHYFQTYBJUILEZ-IUPFWZBJSA-N 0.000 description 4
- 229940117972 triolein Drugs 0.000 description 4
- LINVVMHRTUSXHL-GGVPDPBRSA-N 3beta-hydroxy-5alpha-cholest-8(14)-en-15-one Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1C2=C2C(=O)C[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 LINVVMHRTUSXHL-GGVPDPBRSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 108010089254 Cholesterol oxidase Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 2
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 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
- 238000010521 absorption reaction Methods 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 230000000875 corresponding effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- NPOMSUOUAZCMBL-UHFFFAOYSA-N dichloromethane;ethoxyethane Chemical compound ClCCl.CCOCC NPOMSUOUAZCMBL-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000001030 gas--liquid chromatography Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 210000005229 liver cell Anatomy 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
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 239000003883 ointment base Substances 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- FBPINGSGHKXIQA-UHFFFAOYSA-N 2-amino-3-(2-carboxyethylsulfanyl)propanoic acid Chemical compound OC(=O)C(N)CSCCC(O)=O FBPINGSGHKXIQA-UHFFFAOYSA-N 0.000 description 1
- INBGSXNNRGWLJU-ZHHJOTBYSA-N 25-hydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCCC(C)(C)O)C)[C@@]1(C)CC2 INBGSXNNRGWLJU-ZHHJOTBYSA-N 0.000 description 1
- INBGSXNNRGWLJU-UHFFFAOYSA-N 25epsilon-Hydroxycholesterin Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(CCCC(C)(C)O)C)C1(C)CC2 INBGSXNNRGWLJU-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- CILRIFLDZZZEPV-HYSBADKFSA-N 3β-benzoyloxy-14 α,15α-epoxy-5α-cholest-7-ene Chemical compound O([C@@H]1C[C@@H]2CC=C3[C@]45O[C@H]4C[C@@H]([C@]5(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)C(=O)C1=CC=CC=C1 CILRIFLDZZZEPV-HYSBADKFSA-N 0.000 description 1
- YIKKMWSQVKJCOP-ABXCMAEBSA-N 7-ketocholesterol Chemical compound C1C[C@H](O)CC2=CC(=O)[C@H]3[C@@H]4CC[C@H]([C@H](C)CCCC(C)C)[C@@]4(C)CC[C@@H]3[C@]21C YIKKMWSQVKJCOP-ABXCMAEBSA-N 0.000 description 1
- OMIHGPLIXGGMJB-UHFFFAOYSA-N 7-oxabicyclo[4.1.0]hepta-1,3,5-triene Chemical compound C1=CC=C2OC2=C1 OMIHGPLIXGGMJB-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 101100493710 Caenorhabditis elegans bath-40 gene Proteins 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
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- 238000002441 X-ray diffraction Methods 0.000 description 1
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
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- 210000004369 blood Anatomy 0.000 description 1
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- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
- RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 1
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- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- IHOQNBAZWVTKFK-BVBBTSNESA-N cholesta-5,7-dien-3beta-ol benzoate Chemical compound O([C@@H]1CC2=CC=C3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)C(=O)C1=CC=CC=C1 IHOQNBAZWVTKFK-BVBBTSNESA-N 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- TXCGAZHTZHNUAI-UHFFFAOYSA-N clofibric acid Chemical compound OC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 TXCGAZHTZHNUAI-UHFFFAOYSA-N 0.000 description 1
- 239000003026 cod liver oil Substances 0.000 description 1
- 235000012716 cod liver oil Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- OXZWZJDYOIQKBI-UHFFFAOYSA-L dipotassium sulfate hydrate Chemical compound O.[K+].[K+].[O-]S([O-])(=O)=O OXZWZJDYOIQKBI-UHFFFAOYSA-L 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000000417 fungicide Substances 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
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- ARBOVOVUTSQWSS-UHFFFAOYSA-N hexadecanoyl chloride Chemical compound CCCCCCCCCCCCCCCC(Cl)=O ARBOVOVUTSQWSS-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000011777 magnesium Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000011369 resultant mixture Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000011734 sodium Chemical class 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 229930193551 sterin Natural products 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Obesity (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Child & Adolescent Psychology (AREA)
- Steroid Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/797,345 US4202891A (en) | 1977-05-16 | 1977-05-16 | 15-Oxygenated sterol compounds and the use of such compounds to inhibit the biosynthesis of sterols |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2858726C2 true DE2858726C2 (de) | 1992-10-01 |
Family
ID=25170577
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2858726A Expired - Fee Related DE2858726C2 (de) | 1977-05-16 | 1978-05-16 | Arzneimittel zur senkung des serumcholesterinspiegels |
| DE2858802A Expired - Fee Related DE2858802C2 (de) | 1977-05-16 | 1978-05-16 | Arzneimittel zur unterdrueckung von tumorzellwachstum |
| DE19782821242 Granted DE2821242A1 (de) | 1977-05-16 | 1978-05-16 | 15-oxidierte sterinverbindungen und deren verwendung zur hemmung der biosynthese von sterinen |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2858802A Expired - Fee Related DE2858802C2 (de) | 1977-05-16 | 1978-05-16 | Arzneimittel zur unterdrueckung von tumorzellwachstum |
| DE19782821242 Granted DE2821242A1 (de) | 1977-05-16 | 1978-05-16 | 15-oxidierte sterinverbindungen und deren verwendung zur hemmung der biosynthese von sterinen |
Country Status (11)
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS563000A (en) * | 1979-06-20 | 1981-01-13 | Green Cross Corp:The | Water-soluble cholesterol derivative |
| US5041432A (en) * | 1987-01-30 | 1991-08-20 | E. I. Du Pont De Nemours And Company | Steroid derivatives useful as hypocholesterolemics |
| DE3874763T2 (de) * | 1987-01-30 | 1993-04-01 | Du Pont Merck Pharma | In 14- und 15-stellung substituierte lanosterole und ihre anwendung als hypocholesterolemische mittel. |
| US5034548A (en) * | 1987-01-30 | 1991-07-23 | E. I. Du Pont De Nemours And Company | Steroid derivatives useful as hypocholesterolemics |
| DE3705990A1 (de) * | 1987-02-20 | 1988-09-01 | Schering Ag | 1-methyl-15(alpha)-(1-oxyalkyl)-androsta-1,4-dien- 3,17-dione, verfahren zu deren herstellung und diese enthaltende pharmazeutische praeparate |
| US4897475A (en) * | 1988-02-05 | 1990-01-30 | William Marsh Rice University | Process for synthesis of 5α-cholest-8(14)-en-3β-ol-15-one and other 15-oxygenated sterols |
| US4900477A (en) * | 1988-03-28 | 1990-02-13 | American Cyanamid Company | Novel intermediates and an improved process for producing the compound (3β,5α)-3-hydroxycholest-8(14)-en-15-one |
| US5023250A (en) * | 1989-08-24 | 1991-06-11 | Smithkline Beecham Corporation | Steroidal 14α-carboxy-alkyl derivatives as regulators of HMG-COA reductase |
| US5219879A (en) * | 1990-03-05 | 1993-06-15 | Du Pont Merck Pharmaceutical Company | Heterocyclic steroid compounds |
| JP3029907B2 (ja) * | 1991-12-20 | 2000-04-10 | 理化学研究所 | 抗肥満剤 |
| US5510340A (en) * | 1992-06-12 | 1996-04-23 | Sri International | Antihypercholesterolemic compounds and related pharmaceutical compositions and methods of use |
| US5371077A (en) * | 1992-08-03 | 1994-12-06 | William Marsh Rice University | Side chain derivatized 15-oxygenated sterols, methods of using them and a process for preparing them |
| JP3862295B2 (ja) * | 1993-09-30 | 2006-12-27 | 独立行政法人理化学研究所 | 抗肥満剤 |
| HUP0201098A2 (en) * | 1999-05-10 | 2002-08-28 | Schering Ag | 14betha-h-sterols, pharmaceutical compositions comprising them and use of these derivatives for the preparation of meiosis regulating medicaments |
| US8399441B2 (en) | 2004-10-25 | 2013-03-19 | Virginia Commonwealth University | Nuclear sulfated oxysterol, potent regulator of lipid homeostasis, for therapy of hypercholesterolemia, hypertriglycerides, fatty liver diseases, and atherosclerosis |
| WO2006047022A1 (en) | 2004-10-25 | 2006-05-04 | Virginia Commonwealth University | Nuclear sulfated oxysterol, potent regulator of cholesterol homeostasis, for therapy of hypercholesterolemia, hyperlipidemia, and atherosclerosis |
| US9034859B2 (en) | 2011-04-06 | 2015-05-19 | Virginia Commonwealth University | Sulfated oxysterol and oxysterol sulfation by hydroxysterol sulfotransferase promote lipid homeostasis and liver proliferation |
| HUE057649T2 (hu) | 2013-12-24 | 2022-05-28 | Us Gov Veterans Affairs | Oxigenált koleszterinszulfátok (OCS) alkalmazása az akut májelégtelenség kezelésére |
| JP2019524772A (ja) | 2016-08-02 | 2019-09-05 | ヴァージニア コモンウェルス ユニバーシティ | ５−コレステン−３，２５−ジオール，３−サルフェート（２５ｈｃ３ｓ）又は薬学的に許容される塩及び少なくとも１種の環状オリゴ糖を含む組成物 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1080333A (en) * | 1963-11-01 | 1967-08-23 | Takeda Chemical Industries Ltd | New 14-hydroxy steroids |
| US3354154A (en) * | 1966-01-26 | 1967-11-21 | Syntex Corp | 2beta, 3beta-alkylidenedioxy-6-hydroxy-22, 23-bisnorchol-7-enoic acid alkyl esters and process for the production thereof |
-
1977
- 1977-05-16 US US05/797,345 patent/US4202891A/en not_active Expired - Lifetime
-
1978
- 1978-05-15 CA CA303,354A patent/CA1123739A/en not_active Expired
- 1978-05-16 BE BE187736A patent/BE867120A/xx not_active IP Right Cessation
- 1978-05-16 GB GB19939/78A patent/GB1599863A/en not_active Expired
- 1978-05-16 DE DE2858726A patent/DE2858726C2/de not_active Expired - Fee Related
- 1978-05-16 JP JP5816378A patent/JPS5455734A/ja active Granted
- 1978-05-16 FR FR7814450A patent/FR2390960B1/fr not_active Expired
- 1978-05-16 IT IT49386/78A patent/IT1156745B/it active
- 1978-05-16 CH CH528378A patent/CH641352A5/de not_active IP Right Cessation
- 1978-05-16 AU AU36167/78A patent/AU520703B2/en not_active Expired
- 1978-05-16 NL NL7805267A patent/NL7805267A/xx not_active Application Discontinuation
- 1978-05-16 DE DE2858802A patent/DE2858802C2/de not_active Expired - Fee Related
- 1978-05-16 DE DE19782821242 patent/DE2821242A1/de active Granted
-
1981
- 1981-08-21 FR FR8116129A patent/FR2485021A1/fr active Pending
Non-Patent Citations (3)
| Title |
|---|
| PARISH, E.J. et al.: Tetrahedron Letters, Nr. 42, 1976, S. 3775-3778 * |
| PARISH, E.J. et al.: Tetrahedron Letters, Nr. 49, 1976, S. 4401-4404 * |
| SCHROEPFER, G.J. et al.: Fed.Proc.Am.Soc. Exp.Biol., 35, 1976, S. 1697, Steroids 1714 * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU3616778A (en) | 1979-11-22 |
| JPS5455734A (en) | 1979-05-04 |
| US4202891A (en) | 1980-05-13 |
| GB1599863A (en) | 1981-10-07 |
| BE867120A (fr) | 1978-09-18 |
| IT7849386A0 (it) | 1978-05-16 |
| FR2390960B1 (fr) | 1985-11-29 |
| CH641352A5 (de) | 1984-02-29 |
| CA1123739A (en) | 1982-05-18 |
| FR2390960A1 (fr) | 1978-12-15 |
| DE2821242A1 (de) | 1978-11-23 |
| JPH0214329B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1990-04-06 |
| DE2821242C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1991-10-24 |
| DE2858802C2 (de) | 1991-10-02 |
| AU520703B2 (en) | 1982-02-25 |
| FR2485021A1 (fr) | 1981-12-24 |
| NL7805267A (nl) | 1978-11-20 |
| IT1156745B (it) | 1987-02-04 |
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