AP489A - Steroidal glycosides for treating hypercholesterolemia. - Google Patents

Steroidal glycosides for treating hypercholesterolemia. Download PDF

Info

Publication number: AP489A
Authority: AP; ARIPO
Prior art keywords: carbonyl; cellobiosyl; methylene; alpha; compound according
Prior art date: 1992-06-26

Application number

APAP/P/1993/000539A

Other languages

English (en)

Other versions

AP9300539A0 (en

Inventor

Michael Paul Deninno

Peter Andrew Mccarthy

Original Assignee

Pfizer

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.)

1992-06-26

Filing date

1993-06-17

Publication date

1996-05-02

1993-06-17 Application filed by Pfizer filed Critical Pfizer

1993-07-31 Publication of AP9300539A0 publication Critical patent/AP9300539A0/xx

1996-05-02 Application granted granted Critical

1996-05-02 Publication of AP489A publication Critical patent/AP489A/en

Links

208000035150 Hypercholesterolemia Diseases 0.000 title claims description 16
229930002534 steroid glycoside Natural products 0.000 title abstract description 11
150000008143 steroidal glycosides Chemical class 0.000 title abstract description 8
150000001875 compounds Chemical class 0.000 claims description 251
238000000034 method Methods 0.000 claims description 130
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 90
-1 spirostanyl glycoside Chemical class 0.000 claims description 71
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 65
239000000203 mixture Substances 0.000 claims description 57
239000001257 hydrogen Substances 0.000 claims description 39
229910052739 hydrogen Inorganic materials 0.000 claims description 39
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
INLFWQCRAJUDCR-LYLBMTSKSA-N spirostane Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 INLFWQCRAJUDCR-LYLBMTSKSA-N 0.000 claims description 25
201000001320 Atherosclerosis Diseases 0.000 claims description 10
241000124008 Mammalia Species 0.000 claims description 8
239000008194 pharmaceutical composition Substances 0.000 claims description 8
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 claims description 7
229930182470 glycoside Natural products 0.000 claims description 7
125000001488 beta-D-galactosyl group Chemical group C1([C@H](O)[C@@H](O)[C@@H](O)[C@H](O1)CO)* 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims description 2
230000000879 anti-atherosclerotic effect Effects 0.000 abstract description 4
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
238000002360 preparation method Methods 0.000 description 88
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 60
229910001868 water Inorganic materials 0.000 description 53
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
238000006243 chemical reaction Methods 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
239000000047 product Substances 0.000 description 35
239000000243 solution Substances 0.000 description 32
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 25
239000011734 sodium Substances 0.000 description 23
RTMWIZOXNKJHRE-UHFFFAOYSA-N Tigogenin Natural products CC1COC2CC(C)(OC12)C3CCC4C5CCC6CC(O)CCC6(C)C5CCC34C RTMWIZOXNKJHRE-UHFFFAOYSA-N 0.000 description 22
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 20
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
239000007858 starting material Substances 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
GMBQZIIUCVWOCD-WWASVFFGSA-N Sarsapogenine Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@H](C)CO1 GMBQZIIUCVWOCD-WWASVFFGSA-N 0.000 description 18
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
235000019439 ethyl acetate Nutrition 0.000 description 17
239000012280 lithium aluminium hydride Substances 0.000 description 17
239000007787 solid Substances 0.000 description 17
238000005481 NMR spectroscopy Methods 0.000 description 16
BHHYHSUAOQUXJK-UHFFFAOYSA-L zinc fluoride Chemical compound F[Zn]F BHHYHSUAOQUXJK-UHFFFAOYSA-L 0.000 description 16
238000005859 coupling reaction Methods 0.000 description 15
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
230000008878 coupling Effects 0.000 description 14
238000010168 coupling process Methods 0.000 description 14
239000000725 suspension Substances 0.000 description 14
230000009467 reduction Effects 0.000 description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
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 11
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
229910021529 ammonia Inorganic materials 0.000 description 10
238000003818 flash chromatography Methods 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
239000002904 solvent Substances 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
239000012267 brine Substances 0.000 description 9
230000006196 deacetylation Effects 0.000 description 9
238000003381 deacetylation reaction Methods 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
238000010992 reflux Methods 0.000 description 9
229910052938 sodium sulfate Inorganic materials 0.000 description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 8
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
229940117975 chromium trioxide Drugs 0.000 description 8
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 8
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 8
239000000706 filtrate Substances 0.000 description 8
238000001914 filtration Methods 0.000 description 8
230000000871 hypocholesterolemic effect Effects 0.000 description 8
GMBQZIIUCVWOCD-UQHLGXRBSA-N (25R)-5beta-spirostan-3beta-ol Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)C[C@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 GMBQZIIUCVWOCD-UQHLGXRBSA-N 0.000 description 7
239000012299 nitrogen atmosphere Substances 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
IVURHZJIYJKPLX-UHFFFAOYSA-N spirostan-3,11-diol Chemical compound CC1C(C2(CC(O)C3C4(C)CCC(O)CC4CCC3C2C2)C)C2OC11CCC(C)CO1 IVURHZJIYJKPLX-UHFFFAOYSA-N 0.000 description 7
150000003431 steroids Chemical class 0.000 description 7
239000000126 substance Substances 0.000 description 7
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
239000003795 chemical substances by application Substances 0.000 description 6
235000005911 diet Nutrition 0.000 description 6
230000037213 diet Effects 0.000 description 6
WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 0.000 description 6
238000004821 distillation Methods 0.000 description 6
238000000921 elemental analysis Methods 0.000 description 6
230000003647 oxidation Effects 0.000 description 6
238000007254 oxidation reaction Methods 0.000 description 6
238000003756 stirring Methods 0.000 description 6
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 5
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical class [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 5
235000012000 cholesterol Nutrition 0.000 description 5
230000001906 cholesterol absorption Effects 0.000 description 5
230000001276 controlling effect Effects 0.000 description 5
WQLVFSAGQJTQCK-VKROHFNGSA-N diosgenin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CC[C@H](O)CC4=CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 WQLVFSAGQJTQCK-VKROHFNGSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
239000003480 eluent Substances 0.000 description 5
239000011521 glass Substances 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
239000003550 marker Substances 0.000 description 5
239000000463 material Substances 0.000 description 5
NGYIMTKLQULBOO-UHFFFAOYSA-L mercury dibromide Chemical compound Br[Hg]Br NGYIMTKLQULBOO-UHFFFAOYSA-L 0.000 description 5
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WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
DWCSNWXARWMZTG-UHFFFAOYSA-N Trigonegenin A Natural products CC1C(C2(CCC3C4(C)CCC(O)C=C4CCC3C2C2)C)C2OC11CCC(C)CO1 DWCSNWXARWMZTG-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
238000004458 analytical method Methods 0.000 description 4
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YVPJCJLMRRTDMQ-UHFFFAOYSA-N ethyl diazoacetate Chemical compound CCOC(=O)C=[N+]=[N-] YVPJCJLMRRTDMQ-UHFFFAOYSA-N 0.000 description 4
239000000284 extract Substances 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
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AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 4
229910052943 magnesium sulfate Inorganic materials 0.000 description 4
229940075610 mercuric cyanide Drugs 0.000 description 4
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
229950002323 smilagenin Drugs 0.000 description 4
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229910000033 sodium borohydride Inorganic materials 0.000 description 4
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FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 4
XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
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FCYRSDMGOLYDHL-UHFFFAOYSA-N chloromethoxyethane Chemical compound CCOCCl FCYRSDMGOLYDHL-UHFFFAOYSA-N 0.000 description 2
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UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 1
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PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
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JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
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230000003389 potentiating effect Effects 0.000 description 1
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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
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235000017557 sodium bicarbonate Nutrition 0.000 description 1
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ILJOYZVVZZFIKA-UHFFFAOYSA-M sodium;1,1-dioxo-1,2-benzothiazol-3-olate;hydrate Chemical compound O.[Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 ILJOYZVVZZFIKA-UHFFFAOYSA-M 0.000 description 1
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GDYOHNPSZXFUIG-DSPLKWTLSA-N spirostan-6-one Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4C(=O)C[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CCC(C)CO1 GDYOHNPSZXFUIG-DSPLKWTLSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
- 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
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
General Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Urology & Nephrology (AREA)
Obesity (AREA)
Hematology (AREA)
Diabetes (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Steroid Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

APAP/P/1993/000539A 1992-06-26 1993-06-17 Steroidal glycosides for treating hypercholesterolemia. AP489A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US90491492A	1992-06-26	1992-06-26

Publications (2)

Publication Number	Publication Date
AP9300539A0 AP9300539A0 (en)	1993-07-31
AP489A true AP489A (en)	1996-05-02

Family

ID=25419965

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
APAP/P/1993/000539A AP489A (en)	1992-06-26	1993-06-17	Steroidal glycosides for treating hypercholesterolemia.

Country Status (19)

Country	Link
US (2)	US5629295A (de)
EP (4)	EP0796862A2 (de)
JP (2)	JPH07504921A (de)
KR (1)	KR950702203A (de)
CN (1)	CN1085561A (de)
AP (1)	AP489A (de)
AU (1)	AU4226593A (de)
BG (1)	BG99261A (de)
BR (1)	BR9306619A (de)
CA (1)	CA2139104A1 (de)
CZ (1)	CZ331094A3 (de)
HR (1)	HRP930994A2 (de)
IL (1)	IL106055A0 (de)
MX (1)	MX9303826A (de)
OA (1)	OA10121A (de)
RU (1)	RU94046294A (de)
SK (1)	SK158394A3 (de)
WO (1)	WO1994000480A1 (de)
YU (1)	YU44793A (de)

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1993
- 1993-05-06 US US08/351,470 patent/US5629295A/en not_active Expired - Fee Related
- 1993-05-06 SK SK1583-94A patent/SK158394A3/sk unknown
- 1993-05-06 RU RU94046294/04A patent/RU94046294A/ru unknown
- 1993-05-06 EP EP97200454A patent/EP0796862A2/de not_active Withdrawn
- 1993-05-06 EP EP93910951A patent/EP0647234A1/de not_active Withdrawn
- 1993-05-06 AU AU42265/93A patent/AU4226593A/en not_active Abandoned
- 1993-05-06 CA CA002139104A patent/CA2139104A1/en not_active Abandoned
- 1993-05-06 EP EP97200455A patent/EP0796863A2/de not_active Withdrawn
- 1993-05-06 CZ CZ943310A patent/CZ331094A3/cs unknown
- 1993-05-06 WO PCT/US1993/004092 patent/WO1994000480A1/en not_active Ceased
- 1993-05-06 BR BR9306619A patent/BR9306619A/pt not_active Application Discontinuation
- 1993-05-06 JP JP6502331A patent/JPH07504921A/ja active Pending
- 1993-05-06 EP EP97200456A patent/EP0796864A2/de not_active Withdrawn
- 1993-06-17 AP APAP/P/1993/000539A patent/AP489A/en active
- 1993-06-17 IL IL106055A patent/IL106055A0/xx unknown
- 1993-06-24 HR HR07/904,914A patent/HRP930994A2/xx not_active Application Discontinuation
- 1993-06-25 MX MX9303826A patent/MX9303826A/es unknown
- 1993-06-25 CN CN93107620A patent/CN1085561A/zh active Pending
- 1993-06-25 YU YU44793A patent/YU44793A/sh unknown
1994
- 1994-12-13 BG BG99261A patent/BG99261A/xx unknown
- 1994-12-23 OA OA60598A patent/OA10121A/en unknown
- 1994-12-24 KR KR1019940704728A patent/KR950702203A/ko not_active Ceased
1995
- 1995-06-06 US US08/470,554 patent/US5703052A/en not_active Expired - Fee Related
1997
- 1997-02-14 JP JP9030588A patent/JPH09309897A/ja active Pending

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Also Published As

Publication number	Publication date
JPH07504921A (ja)	1995-06-01
KR950702203A (ko)	1995-06-19
WO1994000480A1 (en)	1994-01-06
IL106055A0 (en)	1993-10-20
EP0796863A2 (de)	1997-09-24
AU4226593A (en)	1994-01-24
CZ331094A3 (en)	1995-09-13
BG99261A (en)	1995-06-30
AP9300539A0 (en)	1993-07-31
MX9303826A (es)	1994-02-28
YU44793A (sh)	1996-10-09
BR9306619A (pt)	1998-12-08
SK158394A3 (en)	1995-05-10
US5629295A (en)	1997-05-13
RU94046294A (ru)	1996-10-10
EP0796864A2 (de)	1997-09-24
JPH09309897A (ja)	1997-12-02
OA10121A (en)	1996-12-18
EP0796862A2 (de)	1997-09-24
CA2139104A1 (en)	1994-01-06
EP0647234A1 (de)	1995-04-12
HRP930994A2 (en)	1996-08-31
US5703052A (en)	1997-12-30
CN1085561A (zh)	1994-04-20

Publication	Publication Date	Title
AP489A (en)	1996-05-02	Steroidal glycosides for treating hypercholesterolemia.
US5939398A (en)	1999-08-17	Hypocholesterolemic agents
GB1599863A (en)	1981-10-07	Pharmaceutical compositions for use in the inhibition of the biosynthesis of mevalonic acid
US5760009A (en)	1998-06-02	Spirostanyl glycosidal crystalline monohydrate
US5698526A (en)	1997-12-16	Steroidal glycosides
US6150336A (en)	2000-11-21	Steroidal glycosides
GB2130587A (en)	1984-06-06	Novel 6a-methylcorticoids and their manufacture and use
WO1996006854A1 (en)	1996-03-07	Spirostanyl glycosidal crystals
US4260464A (en)	1981-04-07	Process for the preparation of 17α-(3-iodobenzoyloxy)-9α-chloro-4-pregnene-3,20-diones and their D-homo homologs
Peters et al.	1987	Steroidal silicon side-chain analogs as potential antifertility agents
EP1422235B1 (de)	2006-10-04	Stereoselektives verfahren zur herstellung von 6alpha-fluorpregnanen und zwischenprodukten
US4353898A (en)	1982-10-12	11α-Amino-androstanes
NO945001L (no)	1995-02-14	Steroide glykosider for behandling av hyperkolestrolemi
EP0149222A2 (de)	1985-07-24	Neue 6alpha, 16alpha-Dimethylkortikoide
US3484436A (en)	1969-12-16	Bicyclo(2.2.2)octane - 1 - -carboxylate esters of delta**4 - pregnene corticoid steroids
US3352890A (en)	1967-11-14	Method of selectively reducing the 3-oxo radical of 3-oxo-6-alpha-methyl-pregn-4-en-20-one compounds
US4127589A (en)	1978-11-28	4,5-Seco-steroids