OA10121A - Steroidal glycosides for treating hypercholesterolemia - Google Patents

Steroidal glycosides for treating hypercholesterolemia Download PDF

Info

Publication number: OA10121A
Authority: OA; OAPI
Prior art keywords: carbonyl; cellobiosyl; methylene; alpha; compound according
Prior art date: 1992-06-26

Application number

OA60598A

Other languages

English (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

1994-12-23

Publication date

1996-12-18

1994-12-23 Application filed by Pfizer filed Critical Pfizer

1996-12-18 Publication of OA10121A publication Critical patent/OA10121A/en

Links

208000035150 Hypercholesterolemia Diseases 0.000 title claims abstract description 15
229930002534 steroid glycoside Natural products 0.000 title description 5
150000008143 steroidal glycosides Chemical class 0.000 title description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 85
-1 spirostanyl glycoside Chemical class 0.000 claims abstract description 63
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract description 57
229930182470 glycoside Natural products 0.000 claims abstract description 12
201000001320 Atherosclerosis Diseases 0.000 claims abstract description 8
150000001875 compounds Chemical class 0.000 claims description 226
238000000034 method Methods 0.000 claims description 113
239000000203 mixture Substances 0.000 claims description 53
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
239000001257 hydrogen Substances 0.000 claims description 37
229910052739 hydrogen Inorganic materials 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 14
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 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 7
239000008194 pharmaceutical composition Substances 0.000 claims description 7
241000124008 Mammalia Species 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 2
239000003814 drug Substances 0.000 abstract description 3
238000004519 manufacturing process Methods 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
229910001868 water Inorganic materials 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
238000006243 chemical reaction Methods 0.000 description 37
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
239000000243 solution Substances 0.000 description 31
239000000047 product Substances 0.000 description 30
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 23
239000011734 sodium Substances 0.000 description 23
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
RTMWIZOXNKJHRE-UHFFFAOYSA-N Tigogenin Natural products CC1COC2CC(C)(OC12)C3CCC4C5CCC6CC(O)CCC6(C)C5CCC34C RTMWIZOXNKJHRE-UHFFFAOYSA-N 0.000 description 19
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 17
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 17
239000007787 solid Substances 0.000 description 15
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
229940073584 methylene chloride Drugs 0.000 description 14
239000007858 starting material Substances 0.000 description 14
BHHYHSUAOQUXJK-UHFFFAOYSA-L zinc fluoride Chemical compound F[Zn]F BHHYHSUAOQUXJK-UHFFFAOYSA-L 0.000 description 14
238000005481 NMR spectroscopy Methods 0.000 description 13
230000008878 coupling Effects 0.000 description 13
238000010168 coupling process Methods 0.000 description 13
238000005859 coupling reaction Methods 0.000 description 13
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IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
235000019439 ethyl acetate Nutrition 0.000 description 12
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
239000011541 reaction mixture Substances 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
239000012280 lithium aluminium hydride Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
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WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 9
239000003795 chemical substances by application Substances 0.000 description 9
229940093499 ethyl acetate Drugs 0.000 description 9
229910052744 lithium Inorganic materials 0.000 description 9
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
239000012267 brine Substances 0.000 description 8
230000006196 deacetylation Effects 0.000 description 8
238000003381 deacetylation reaction Methods 0.000 description 8
230000000694 effects Effects 0.000 description 8
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
238000010992 reflux Methods 0.000 description 8
229910052938 sodium sulfate Inorganic materials 0.000 description 8
235000011152 sodium sulphate Nutrition 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
229910021529 ammonia Inorganic materials 0.000 description 7
229940117975 chromium trioxide Drugs 0.000 description 7
WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 7
GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
150000002338 glycosides Chemical class 0.000 description 7
150000003431 steroids Chemical class 0.000 description 7
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 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
239000002253 acid Substances 0.000 description 6
238000000921 elemental analysis Methods 0.000 description 6
238000003818 flash chromatography Methods 0.000 description 6
150000004678 hydrides Chemical class 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
239000000741 silica gel Substances 0.000 description 6
229910002027 silica gel Inorganic materials 0.000 description 6
238000003756 stirring Methods 0.000 description 6
239000000126 substance Substances 0.000 description 6
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 5
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 5
WQLVFSAGQJTQCK-UHFFFAOYSA-N diosgenin Natural products CC1C(C2(CCC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 WQLVFSAGQJTQCK-UHFFFAOYSA-N 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
238000004821 distillation Methods 0.000 description 5
239000003480 eluent Substances 0.000 description 5
150000004820 halides Chemical class 0.000 description 5
235000011167 hydrochloric acid Nutrition 0.000 description 5
229960000443 hydrochloric acid Drugs 0.000 description 5
239000003550 marker Substances 0.000 description 5
NGYIMTKLQULBOO-UHFFFAOYSA-L mercury dibromide Chemical compound Br[Hg]Br NGYIMTKLQULBOO-UHFFFAOYSA-L 0.000 description 5
230000003647 oxidation Effects 0.000 description 5
238000007254 oxidation reaction Methods 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 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
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical class [Na+].OS([O-])=O DWAQJAXMDSEUJJ-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
238000004458 analytical method Methods 0.000 description 4
235000005911 diet Nutrition 0.000 description 4
230000037213 diet Effects 0.000 description 4
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
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 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
239000012279 sodium borohydride Substances 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
238000003786 synthesis reaction Methods 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
RTKMFQOHBDVEBC-UHFFFAOYSA-N 3-bromo-3-buten-1-ol Chemical compound OCCC(Br)=C RTKMFQOHBDVEBC-UHFFFAOYSA-N 0.000 description 3
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 3
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DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
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241001465754 Metazoa Species 0.000 description 3
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235000019270 ammonium chloride Nutrition 0.000 description 3
230000000879 anti-atherosclerotic effect Effects 0.000 description 3
210000000709 aorta Anatomy 0.000 description 3
239000000010 aprotic solvent Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
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229910052794 bromium Inorganic materials 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
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150000002632 lipids Chemical class 0.000 description 3
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INLFWQCRAJUDCR-IQVMEADQSA-N (1R,2S,4S,5'S,6R,7S,8R,9S,12S,13S)-5',7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.02,9.04,8.013,18]icosane-6,2'-oxane] 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-IQVMEADQSA-N 0.000 description 2
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NWMIYTWHUDFRPL-UHFFFAOYSA-N sapogenin Natural products COC(=O)C1(CO)C(O)CCC2(C)C1CCC3(C)C2CC=C4C5C(C)(O)C(C)CCC5(CCC34C)C(=O)O NWMIYTWHUDFRPL-UHFFFAOYSA-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)

OA60598A 1992-06-26 1994-12-23 Steroidal glycosides for treating hypercholesterolemia OA10121A (en)

Applications Claiming Priority (1)

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

Publications (1)

Publication Number	Publication Date
OA10121A true OA10121A (en)	1996-12-18

Family

ID=25419965

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA60598A OA10121A (en)	1992-06-26	1994-12-23	Steroidal glycosides for treating hypercholesterolemia

Country Status (19)

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

Families Citing this family (54)

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1993
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- 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/fr not_active Withdrawn
- 1993-05-06 EP EP93910951A patent/EP0647234A1/fr not_active Withdrawn
- 1993-05-06 AU AU42265/93A patent/AU4226593A/en not_active Abandoned
- 1993-05-06 CA CA002139104A patent/CA2139104A1/fr not_active Abandoned
- 1993-05-06 EP EP97200455A patent/EP0796863A2/fr not_active Withdrawn
- 1993-05-06 CZ CZ943310A patent/CZ331094A3/cs unknown
- 1993-05-06 WO PCT/US1993/004092 patent/WO1994000480A1/fr 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/fr 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

Also Published As

Publication number	Publication date
JPH07504921A (ja)	1995-06-01
KR950702203A (ko)	1995-06-19
WO1994000480A1 (fr)	1994-01-06
IL106055A0 (en)	1993-10-20
EP0796863A2 (fr)	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
AP489A (en)	1996-05-02
EP0796864A2 (fr)	1997-09-24
JPH09309897A (ja)	1997-12-02
EP0796862A2 (fr)	1997-09-24
CA2139104A1 (fr)	1994-01-06
EP0647234A1 (fr)	1995-04-12
HRP930994A2 (en)	1996-08-31
US5703052A (en)	1997-12-30
CN1085561A (zh)	1994-04-20

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