NZ545087A - Novel compounds and compositions comprising sterols and/or stanols and cholesterol biosynthesis inhibitors and use thereof in treating or preventing a variety of diseases and conditions - Google Patents
Novel compounds and compositions comprising sterols and/or stanols and cholesterol biosynthesis inhibitors and use thereof in treating or preventing a variety of diseases and conditionsInfo
- Publication number
- NZ545087A NZ545087A NZ545087A NZ54508704A NZ545087A NZ 545087 A NZ545087 A NZ 545087A NZ 545087 A NZ545087 A NZ 545087A NZ 54508704 A NZ54508704 A NZ 54508704A NZ 545087 A NZ545087 A NZ 545087A
- Authority
- NZ
- New Zealand
- Prior art keywords
- preventing
- treating
- alleviating
- formulae
- linked
- Prior art date
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 abstract 30
- 150000001875 compounds Chemical class 0.000 title claims abstract 20
- 230000015572 biosynthetic process Effects 0.000 title claims abstract 15
- 235000012000 cholesterol Nutrition 0.000 title claims abstract 15
- 239000003112 inhibitor Substances 0.000 title claims abstract 15
- 229930182558 Sterol Natural products 0.000 title claims abstract 11
- 150000003432 sterols Chemical class 0.000 title claims abstract 11
- 235000003702 sterols Nutrition 0.000 title claims abstract 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims 7
- 239000000203 mixture Substances 0.000 title claims 5
- 201000010099 disease Diseases 0.000 title claims 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 10
- 229910052760 oxygen Inorganic materials 0.000 claims abstract 9
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract 8
- 150000003839 salts Chemical class 0.000 claims abstract 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 5
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims abstract 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract 5
- 239000001257 hydrogen Substances 0.000 claims abstract 5
- 229910052751 metal Inorganic materials 0.000 claims abstract 5
- 239000002184 metal Substances 0.000 claims abstract 5
- 239000001301 oxygen Substances 0.000 claims abstract 5
- 239000012453 solvate Substances 0.000 claims abstract 5
- 229960005070 ascorbic acid Drugs 0.000 claims abstract 4
- 235000010323 ascorbic acid Nutrition 0.000 claims abstract 4
- 239000011668 ascorbic acid Substances 0.000 claims abstract 4
- 230000002708 enhancing effect Effects 0.000 claims 8
- 230000001747 exhibiting effect Effects 0.000 claims 8
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 claims 7
- 108010046315 IDL Lipoproteins Proteins 0.000 claims 6
- 230000003247 decreasing effect Effects 0.000 claims 6
- 238000000034 method Methods 0.000 claims 6
- 230000003647 oxidation Effects 0.000 claims 6
- 238000007254 oxidation reaction Methods 0.000 claims 6
- 210000002966 serum Anatomy 0.000 claims 6
- 201000001320 Atherosclerosis Diseases 0.000 claims 4
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims 4
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims 4
- 108010022535 Farnesyl-Diphosphate Farnesyltransferase Proteins 0.000 claims 4
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 claims 4
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 claims 4
- 108010000775 Hydroxymethylglutaryl-CoA synthase Proteins 0.000 claims 4
- 102100028888 Hydroxymethylglutaryl-CoA synthase, cytoplasmic Human genes 0.000 claims 4
- 208000035150 Hypercholesterolemia Diseases 0.000 claims 4
- 206010061218 Inflammation Diseases 0.000 claims 4
- 108010007622 LDL Lipoproteins Proteins 0.000 claims 4
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims 4
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims 4
- 102000005782 Squalene Monooxygenase Human genes 0.000 claims 4
- 108020003891 Squalene monooxygenase Proteins 0.000 claims 4
- 102100037997 Squalene synthase Human genes 0.000 claims 4
- 108010062497 VLDL Lipoproteins Proteins 0.000 claims 4
- 229960005370 atorvastatin Drugs 0.000 claims 4
- 230000002860 competitive effect Effects 0.000 claims 4
- 208000029078 coronary artery disease Diseases 0.000 claims 4
- 208000035475 disorder Diseases 0.000 claims 4
- 230000004054 inflammatory process Effects 0.000 claims 4
- 229960004844 lovastatin Drugs 0.000 claims 4
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims 4
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 229960002855 simvastatin Drugs 0.000 claims 4
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims 4
- LGJMUZUPVCAVPU-HRJGVYIJSA-N stigmastanol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@@H](CC)C(C)C)[C@@]2(C)CC1 LGJMUZUPVCAVPU-HRJGVYIJSA-N 0.000 claims 4
- BFDNMXAIBMJLBB-UHFFFAOYSA-N stigmasterol Natural products CCC(C=CC(C)C1CCCC2C3CC=C4CC(O)CCC4(C)C3CCC12C)C(C)C BFDNMXAIBMJLBB-UHFFFAOYSA-N 0.000 claims 4
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims 4
- OSELKOCHBMDKEJ-UHFFFAOYSA-N (10R)-3c-Hydroxy-10r.13c-dimethyl-17c-((R)-1-methyl-4-isopropyl-hexen-(4c)-yl)-(8cH.9tH.14tH)-Delta5-tetradecahydro-1H-cyclopenta[a]phenanthren Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(=CC)C(C)C)C1(C)CC2 OSELKOCHBMDKEJ-UHFFFAOYSA-N 0.000 claims 3
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 claims 3
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims 3
- 229960002965 pravastatin Drugs 0.000 claims 3
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims 3
- NLQLSVXGSXCXFE-UHFFFAOYSA-N sitosterol Natural products CC=C(/CCC(C)C1CC2C3=CCC4C(C)C(O)CCC4(C)C3CCC2(C)C1)C(C)C NLQLSVXGSXCXFE-UHFFFAOYSA-N 0.000 claims 3
- MCWVPSBQQXUCTB-UHFFFAOYSA-N (24Z)-5alpha-Stigmasta-7,24(28)-dien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(=CC)C(C)C)CCC33)C)C3=CCC21 MCWVPSBQQXUCTB-UHFFFAOYSA-N 0.000 claims 2
- SGNBVLSWZMBQTH-ZRUUVFCLSA-N 24-epicampesterol 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)CC[C@H](C)C(C)C)[C@@]1(C)CC2 SGNBVLSWZMBQTH-ZRUUVFCLSA-N 0.000 claims 2
- ARYTXMNEANMLMU-UHFFFAOYSA-N 24alpha-methylcholestanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(C)C(C)C)C1(C)CC2 ARYTXMNEANMLMU-UHFFFAOYSA-N 0.000 claims 2
- CQSRUKJFZKVYCY-UHFFFAOYSA-N 5alpha-isofucostan-3beta-ol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(=CC)C(C)C)C1(C)CC2 CQSRUKJFZKVYCY-UHFFFAOYSA-N 0.000 claims 2
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 claims 2
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
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- 101710115418 Apolipoprotein(a) Proteins 0.000 claims 2
- 102100040214 Apolipoprotein(a) Human genes 0.000 claims 2
- 206010003210 Arteriosclerosis Diseases 0.000 claims 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
- 206010012289 Dementia Diseases 0.000 claims 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 2
- BTEISVKTSQLKST-UHFFFAOYSA-N Haliclonasterol Natural products CC(C=CC(C)C(C)(C)C)C1CCC2C3=CC=C4CC(O)CCC4(C)C3CCC12C BTEISVKTSQLKST-UHFFFAOYSA-N 0.000 claims 2
- 206010020772 Hypertension Diseases 0.000 claims 2
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- OSELKOCHBMDKEJ-VRUYXKNBSA-N Isofucosterol Natural products CC=C(CC[C@@H](C)[C@H]1CC[C@@H]2[C@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C)C(C)C OSELKOCHBMDKEJ-VRUYXKNBSA-N 0.000 claims 2
- 238000008214 LDL Cholesterol Methods 0.000 claims 2
- 108090001030 Lipoproteins Proteins 0.000 claims 2
- 102000004895 Lipoproteins Human genes 0.000 claims 2
- 208000001132 Osteoporosis Diseases 0.000 claims 2
- LGJMUZUPVCAVPU-JFBKYFIKSA-N Sitostanol Natural products O[C@@H]1C[C@H]2[C@@](C)([C@@H]3[C@@H]([C@H]4[C@@](C)([C@@H]([C@@H](CC[C@H](C(C)C)CC)C)CC4)CC3)CC2)CC1 LGJMUZUPVCAVPU-JFBKYFIKSA-N 0.000 claims 2
- 208000007536 Thrombosis Diseases 0.000 claims 2
- QYIXCDOBOSTCEI-UHFFFAOYSA-N alpha-cholestanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCCC(C)C)C1(C)CC2 QYIXCDOBOSTCEI-UHFFFAOYSA-N 0.000 claims 2
- JZVFJDZBLUFKCA-UTQQLQBSSA-N alpha-spinasterol Natural products CC[C@H](C=C[C@H](C)[C@H]1CC[C@H]2C3=CC[C@@H]4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C JZVFJDZBLUFKCA-UTQQLQBSSA-N 0.000 claims 2
- 230000002491 angiogenic effect Effects 0.000 claims 2
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- MCWVPSBQQXUCTB-OQTIOYDCSA-N avenasterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)CC/C(=C/C)C(C)C)CC[C@H]33)C)C3=CC[C@H]21 MCWVPSBQQXUCTB-OQTIOYDCSA-N 0.000 claims 2
- NJKOMDUNNDKEAI-UHFFFAOYSA-N beta-sitosterol Natural products CCC(CCC(C)C1CCC2(C)C3CC=C4CC(O)CCC4C3CCC12C)C(C)C NJKOMDUNNDKEAI-UHFFFAOYSA-N 0.000 claims 2
- 210000000988 bone and bone Anatomy 0.000 claims 2
- 230000008416 bone turnover Effects 0.000 claims 2
- ARYTXMNEANMLMU-ATEDBJNTSA-N campestanol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@@H](C)C(C)C)[C@@]2(C)CC1 ARYTXMNEANMLMU-ATEDBJNTSA-N 0.000 claims 2
- 230000001413 cellular effect Effects 0.000 claims 2
- KZJWDPNRJALLNS-FBZNIEFRSA-N clionasterol 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)CC[C@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-FBZNIEFRSA-N 0.000 claims 2
- QYIXCDOBOSTCEI-NWKZBHTNSA-N coprostanol Chemical compound C([C@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CCCC(C)C)[C@@]2(C)CC1 QYIXCDOBOSTCEI-NWKZBHTNSA-N 0.000 claims 2
- 230000006378 damage Effects 0.000 claims 2
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- OSELKOCHBMDKEJ-WGMIZEQOSA-N isofucosterol 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)CC/C(=C/C)C(C)C)[C@@]1(C)CC2 OSELKOCHBMDKEJ-WGMIZEQOSA-N 0.000 claims 2
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- 150000002632 lipids Chemical class 0.000 claims 2
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- 230000036542 oxidative stress Effects 0.000 claims 2
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- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol 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)/C=C/[C@@H](CC)C(C)C)[C@@]1(C)CC2 HCXVJBMSMIARIN-PHZDYDNGSA-N 0.000 claims 2
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- CSVWWLUMXNHWSU-UHFFFAOYSA-N (22E)-(24xi)-24-ethyl-5alpha-cholest-22-en-3beta-ol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(CC)C(C)C)C1(C)CC2 CSVWWLUMXNHWSU-UHFFFAOYSA-N 0.000 claims 1
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- BDCFUHIWJODVNG-UHFFFAOYSA-N Desmosterol Natural products C1C=C2CC(O)C=CC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 BDCFUHIWJODVNG-UHFFFAOYSA-N 0.000 claims 1
- DNVPQKQSNYMLRS-NXVQYWJNSA-N Ergosterol Natural products CC(C)[C@@H](C)C=C[C@H](C)[C@H]1CC[C@H]2C3=CC=C4C[C@@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C DNVPQKQSNYMLRS-NXVQYWJNSA-N 0.000 claims 1
- GBBBJSKVBYJMBG-QTWVXCTBSA-N Fucosterol Natural products CC=C(CC[C@@H](C)[C@@H]1CC[C@@H]2[C@H]3C=C[C@@H]4C[C@H](O)CC[C@@]4(C)[C@@H]3CC[C@@]12C)C(C)C GBBBJSKVBYJMBG-QTWVXCTBSA-N 0.000 claims 1
- CQSRUKJFZKVYCY-WZJYZIMXSA-N Isofucostanol Chemical compound C/C=C(/CCC(C)[C@H]1CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2CCC4[C@@]3(CCC(C4)O)C)C)\C(C)C CQSRUKJFZKVYCY-WZJYZIMXSA-N 0.000 claims 1
- JZVFJDZBLUFKCA-INYURWPISA-N Poriferasta-7,22E-dien-3beta-ol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)/C=C/[C@H](CC)C(C)C)CC[C@H]33)C)C3=CC[C@H]21 JZVFJDZBLUFKCA-INYURWPISA-N 0.000 claims 1
- HCXVJBMSMIARIN-LWINXXIXSA-N Poriferasterol Natural products CC[C@H](C=C[C@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)C(C)C HCXVJBMSMIARIN-LWINXXIXSA-N 0.000 claims 1
- OILXMJHPFNGGTO-ZRUUVFCLSA-N UNPD197407 Natural products C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)C=C[C@H](C)C(C)C)[C@@]1(C)CC2 OILXMJHPFNGGTO-ZRUUVFCLSA-N 0.000 claims 1
- HZYXFRGVBOPPNZ-UHFFFAOYSA-N UNPD88870 Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)=CCC(CC)C(C)C)C1(C)CC2 HZYXFRGVBOPPNZ-UHFFFAOYSA-N 0.000 claims 1
- JZVFJDZBLUFKCA-FXIAWGAOSA-N alpha-Spinasterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@@H](CC[C@@]3([C@@H]([C@H](C)/C=C/[C@@H](CC)C(C)C)CC[C@H]33)C)C3=CC[C@H]21 JZVFJDZBLUFKCA-FXIAWGAOSA-N 0.000 claims 1
- SLQKYSPHBZMASJ-UHFFFAOYSA-N bastadin-1 Natural products CC12CCC(O)CC1CCC1=C2CCC2(C)C(C(C)CCC(=C)C(C)C)CCC21 SLQKYSPHBZMASJ-UHFFFAOYSA-N 0.000 claims 1
- MJVXAPPOFPTTCA-UHFFFAOYSA-N beta-Sistosterol Natural products CCC(CCC(C)C1CCC2C3CC=C4C(C)C(O)CCC4(C)C3CCC12C)C(C)C MJVXAPPOFPTTCA-UHFFFAOYSA-N 0.000 claims 1
- OILXMJHPFNGGTO-ZAUYPBDWSA-N brassicasterol 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)/C=C/[C@H](C)C(C)C)[C@@]1(C)CC2 OILXMJHPFNGGTO-ZAUYPBDWSA-N 0.000 claims 1
- 235000004420 brassicasterol Nutrition 0.000 claims 1
- SGNBVLSWZMBQTH-PODYLUTMSA-N campesterol 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)CC[C@@H](C)C(C)C)[C@@]1(C)CC2 SGNBVLSWZMBQTH-PODYLUTMSA-N 0.000 claims 1
- 235000000431 campesterol Nutrition 0.000 claims 1
- -1 chalinosterol Chemical compound 0.000 claims 1
- AVSXSVCZWQODGV-DPAQBDIFSA-N desmosterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CCC=C(C)C)C)[C@@]1(C)CC2 AVSXSVCZWQODGV-DPAQBDIFSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- IBAFJAONJZIYIT-UHFFFAOYSA-N epicodisterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(CCC(C)C(C)=C)C)C1(C)CC2 IBAFJAONJZIYIT-UHFFFAOYSA-N 0.000 claims 1
- DNVPQKQSNYMLRS-SOWFXMKYSA-N ergosterol Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H](CC[C@]3([C@H]([C@H](C)/C=C/[C@@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 DNVPQKQSNYMLRS-SOWFXMKYSA-N 0.000 claims 1
- YYLFLRIUDMIWTD-UHFFFAOYSA-N ethyldesmosterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)=C(C)C)C1(C)CC2 YYLFLRIUDMIWTD-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- BALNAVKTUKBYSD-UHFFFAOYSA-N nervisterol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C(C)C)C(C)=C)C1(C)CC2 BALNAVKTUKBYSD-UHFFFAOYSA-N 0.000 claims 1
- STLJXSQSUAPXFX-UHFFFAOYSA-N peposterol Chemical compound C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)=C(C)C)CCC33)C)C3=CCC21 STLJXSQSUAPXFX-UHFFFAOYSA-N 0.000 claims 1
- LGJMUZUPVCAVPU-GJAZBXDESA-N poriferastan-3beta-ol Chemical compound C([C@@H]1CC2)[C@@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@H](CC)C(C)C)[C@@]2(C)CC1 LGJMUZUPVCAVPU-GJAZBXDESA-N 0.000 claims 1
- KZJWDPNRJALLNS-VJSFXXLFSA-N sitosterol 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)CC[C@@H](CC)C(C)C)[C@@]1(C)CC2 KZJWDPNRJALLNS-VJSFXXLFSA-N 0.000 claims 1
- 235000015500 sitosterol Nutrition 0.000 claims 1
- 229950005143 sitosterol Drugs 0.000 claims 1
- GHIZCSMTYWOBQA-BZSCQJQFSA-N spinasterol Natural products CC[C@H](C=C[C@@H](C)[C@@H]1CC[C@@]2(C)C3=CC[C@@H]4C[C@H](O)CC[C@]4(C)[C@@H]3CC[C@]12C)C(C)C GHIZCSMTYWOBQA-BZSCQJQFSA-N 0.000 claims 1
- QOXPZVASXWSKKU-UHFFFAOYSA-N stellasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(C)C(C)C)CCC33)C)C3=CCC21 QOXPZVASXWSKKU-UHFFFAOYSA-N 0.000 claims 1
- 235000016831 stigmasterol Nutrition 0.000 claims 1
- 229940032091 stigmasterol Drugs 0.000 claims 1
Classifications
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- 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
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- 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
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- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
Disclosed is a compound comprising a sterol or stanol, including biologically acceptable salts thereof, having one or more of the formulae a-f wherein R is a sterol or stanol moiety, R2 is a cholesterol biosynthesis inhibitor with at least one free and reactive carboxyl group; R3 is a cholesterol biosynthesis inhibitor with at least one free and reactive hydroxyl group; R4 is derived from ascorbic acid, X is either hydrogen or is selected from the group consisting of a biologically acceptable metal, or an alkali earth metal and n = 1-5, including all biologically acceptable salts or solvates thereof; wherein R is linked in formulae b), c), d) or f) via oxygen, R2 is linked in formulae b), c), d) or f) via a carboxyl function, and R3 is linked in formulae b), c), d) or f) via a hydroxyl group.
Claims (9)
1.WE CLAIM: 1. A compound comprising a sterol or stanol, including biologically acceptable salts thereof, having one or more of the following formulae: a) o R2 —(CH2)n —C —O —R b) R2—R , with the proviso that R2 is not linked to R via a linker Y-CO-CH2-CH2-CO-O-, wherein Y is O or NH; c) o o ii ii r2—c— c-o-r d) 0 ii r3— p—o-r 1 ox e) 0 R2—R, —P —0—R 1 ox f) o o r3—p-r4 -p-o-r ix ix wherein R is a sterol or stanol moiety, R2 is a cholesterol biosynthesis inhibitor with at 545087 least one free and reactive carboxyl group; R3 is a cholesterol biosynthesis inhibitor with at least one free and reactive hydroxyl group; R4 is derived from ascorbic acid, X is either hydrogen or is selected from the group consisting of a biologically acceptable metal, or an alkali earth metal and n=1-5, including all biologically acceptable salts or solvates thereof; wherein R is linked in formulae b), c), d) or f) via oxygen, R2 is linked in formulae b), c), d) or f) via a carboxyl function, and R3 is linked in formulae b), c), d) or f) via a hydroxyl group.
2. A compound according to claim 1, having the formulae a), c), d), e) or f) as defined in claim 1.
3. The compound of claim 1 or claim 2 wherein the sterol is selected from the group consisting of sitosterol, campesterol, stigmasterol, brassicasterol (including dihydrobrassicasterol), desmosterol, chalinosterol, poriferasterol, clionasterol, ergosterol, coprosterol, codisterol, isofucosterol, fucosterol, clerosterol, nervisterol, lathosterol, stellasterol, spinasterol, chondrillasterol, peposterol, avenasterol, isoavenasterol, fecosterol, and pollinastasterol.
4. The compound of claim 1 or claim 2 wherein the stanol is selected from the group consisting of sitostanol, campestanol, stigmastanol, brassicastano! (including dihydrobrassicastanol), desmostanol, chalinostanol, poriferastanol, clionastanol, ergostanol, coprostanol, codistanol, isofucostanol, fucostanol, clerostanol, nervistanol, lathostanol, stellastanol, spinastanol, chondrillastanol, pepostanol, avenastanol, isoavenastanol, fecostanol, and poflinastastanol.
5. The compound of claim 1 or claim 2 wherein the sterol and stanol are in either a natural or artificially synthesized form.
6. The compound of claim 1 or claim 2 wherein the sterol and stanoi are in any one of their isomeric forms.
7. The compound of claim 1 or claim 2 wherein the R2 and R3 are selected from the group consisting of competitive inhibitors of HMG CoA reductase, HMG CoA synthase, squalene synthase, and squalene epoxidase.
8. The compound of claim 1 or claim 2 wherein R2 is either atorvastatin or pravastatin.
9. The compound of claim 1 or claim 2 wherein R3 is either simvastatin or lovastatin. 0FF'ce ySfSrT '< SEP to# 49 3uoci oi c\aW 545087 1 having the following formula: AV ^ecomP°' •*<*»** ln91t"mUla'' -vCW HO, r / 12. the coroP00' rt><*d»w' V\avVnQ t^e^ftoWvn9 forrn^3' HO. HO b"M® w .,*-Ar - -s H,C so comP' ,0uomPoun< V\avVr*9 ^oWo^Q ^ocm^a- ■\5. the compo' Df da,rn H4C . „ fnrtn^a- tbefo«°^n9 -* ^ having HaP ,Cfts 51 545087 16. The compound of claim 1 having the following formula: 17. The compound of claim 1 having the following formula: 18. A pharmaceutical composition comprising at least one compound having one or more of the following formulae: a) o r2-~) r2—R , with the proviso that R2 is not linked to R via a linker Y-CO-CH2-CH2-CO-O-, wherein Y is O or NH; c) e) o R2—R4 —p—o-r ! ox 52 545087 O O II u r3—p —fu -p -o-r OX OX wherein R is a sterol or stanof moiety, R2 is a cholesterol biosynthesis inhibitor with at least one free and reactive carboxyl group; R3 is a cholesterol biosynthesis inhibitor with at least one free and reactive hydroxyl group; R4 is derived from ascorbic add, X is either hydrogen or is selected from the group consisting of a biologically acceptable metal, or an alkali earth metal and n=1-5, including all biologically acceptable salts or solvates thereof and a pharmaceutically acceptable carrier therefor; wherein R is linked in formulae b), c), d) or f) via oxygen, R2 is linked in formulae b), c), d) or f) via a carboxyl function, and R3 is linked in formulae b), c), d) or f) via a hydroxyl group. 19. A pharmaceutical composition according to claim 18, wherein the composition comprises a compound having the formulae a), c), d), e) orf) as defined in claim 18. 20. The composition of claim 18 or 19 wherein R2 and R3 are selected from the group consisting of competitive inhibitors of HMG CoA reductase, HMG CoA synthase, squalene synthase, and squalene epoxidase. 21. The composition of claim 18 or 19 wherein R2 is either atorvastatin or provastatin. 22. The composition of claim 18 or 19 wherein R3 is either simvastatin or lovastatin. 23. Use of a non-toxic and therapeutically effective amount of one or more compounds having the following formulae: a) b) r2 r , with the proviso that R2 is not linked to R via a linker Y-C0-CH2-CH2-C0-0-, wherein Y is O or NH; r2 {ch2)n —c —o —r O II 53 c) O O 545087 It JJ Rg —C *—C —*O —R d) o R3 —P —O -R ix e) o r2_a, —p—o—r 6x f) 0 o i! » R3— P— R4-P-0-R 1 1 ox ox wherein R is a sterol or stanol moiety, R2 is a cholesterol biosynthesis inhibitor with at least one free and reactive carboxyl group; R3 is a cholesterol biosynthesis inhibitor with at least one free and reactive hydroxyl group; R4 is derived from ascorbic acid, X is either hydrogen or is selected from the group consisting of a biologically acceptable metal, or an alkali earth metal and n=1-5, including all biologically acceptable salts or solvates thereof; wherein R is linked in formulae b), c), d) or f) via oxygen, R2 is linked in formulae b), c), d) or f) via a carboxyl function, and R3 is linked in formulae b), c), d) or f) via a hydroxyl group; for the manufacture of a pharmaceutical composition for achieving one or more of the following therapeutic goals: a) preventing, treating or alleviating one or more conditions associated with CVD generally and including arteriosclerosis, atherosclerosis, arteriolosclerosis, angina pectoris, and thrombosis; b) reducing and/or eliminating one or more of the risk factors associated with CVD c) preventing, treating or alleviating atherosclerosis; d) preventing, treating or alleviating hypercholesterolemia; e) preventing, treating or alleviating a hyperlipidic condition; f) preventing, treating or alleviating dislipidemia; g) preventing, treating or alleviating hypertension; h) preventing, treating or alleviating coronary artery disease; i) preventing, treating or alleviating coronary plaque development; M SEP ftEC fziy |p n 54 545087 j) preventing, treating or alleviating coronary plaque inflammation; k) lowering serum LDL cholesterol; I) increasing serum HDL cholesterol; m) decreasing serum triglycerides levels; n) decreasing cholesterol biosynthesis; o) preventing, reducing, eliminating or ameliorating a dislipidemic condition or disorder; p) preventing, reducing, eliminating or ameliorating hypercholesterolemia or hypoalphalipoproteinemia, q) preventing, reducing, eliminating, stabilizing or ameliorating the development of atherosclerotic lesions or plaque; r) preventing, reducing, eliminating, or ameliorating the development of inflammation associated with the development of cardiovascular disease and coronary artery disease; s) preventing, reducing, eliminating or ameliorating any condition, disease or disorder which has as its basis or which is exacerbated by a deficiency in plasma HDL, or by an excess of either LDL, VLDL, Lp(a), beta-VLDL, IDL or remnant lipoproteins; t) decreasing the risk of a stroke; u) inhibition of isoprenoid synthesis; v) preventing, treating or alleviating Alzheimer's disease; w) preventing, treating or alleviating dementia; x) preventing, treating or alleviating osteoporosis; y) preventing, reducing, eliminating or ameliorating injuries due to oxidative stress; z) enhancing and/or preserving the stability of HDL from oxidation; aa)enhancing and/or preserving the stability of LDL, VLDL or IDL from oxidation bb)enhancing and/or preserving the stability of triglyceride (TG) from oxidation; cc) exhibiting anti-coagulatant properties; dd)exhibiting anti-proliferative properties; ee)exhibiting immunomodulatory properties; ff) exhibiting angiogenic properties; gg)preventing, treating or alleviating tumour growth; hh)increasing bone mass and/or bone turnover; and ii) enhancing any of the non-lipid related, pleiotropic effects administration of statins, in particular at the cellular and molecular level. INIfu© 0/r$eVftfi«ry u s& 2009 / V£ 55 545087 24. A use according to claim 23, wherein the compound has the formula a), c), d), e) or f) as defined in claim 23. 25. The use of claim 23 or 24 wherein R2 and R3 are selected from the group consisting of competitive inhibitors of HMG CoA reductase, HMG CoA synthase, squalene synthase, and squalene epoxidase. 26. The use of claim 23 or 24 wherein R2 is either atorvastatin or pravastatin. 27. The use of claim 23 or 24 wherein R3 is either simvastatin or lovastatin. 28. A method of achieving one or more of the following therapeutic goals in a non-human animal: a) preventing, treating or alleviating one or more conditions associated with CVD generally and including arteriosclerosis, atherosclerosis, arteriolosclerosis, angina pectoris, and thrombosis; b) reducing and/or eliminating one or more of the risk factors associated with CVD c) preventing, treating or alleviating atherosclerosis; d) preventing, treating or alleviating hypercholesterolemia; e) preventing, treating or alleviating a hyperlipidic condition; f) preventing, treating or alleviating dislipidemia; g) preventing, treating or alleviating hypertension; h) preventing, treating or alleviating coronary artery disease; i) preventing, treating or alleviating coronary plaque development; j) preventing, treating or alleviating coronary plaque inflammation; k) lowering serum LDL cholesterol; I) increasing serum HDL cholesterol; m) decreasing serum triglycerides levels; n) decreasing cholesterol biosynthesis; o) preventing, reducing, eliminating or ameliorating a dislipidemic condition or disorder; p) preventing, reducing, eliminating or ameliorating hypercholesterolemia or hypoalphalipoproteinemia, q) preventing, reducing, eliminating, stabilizing or ameliorating the development of atherosclerotic lesions or plaque; r) preventing, reducing, eliminating, or ameliorating the development of inflammation associated with the development of cardiovascular disease and coronary artery disease; 56 545087 s) preventing, reducing, eliminating or ameliorating any condition, disease or disorder which has as its basis or which is exacerbated by a deficiency in plasma HDL, or by an excess of either LDL, VLDL, Lp(a), beta-VLDL. IDL or remnant lipoproteins; t) decreasing the risk of a stroke; u) inhibition of isoprenoid synthesis; v) preventing, treating or alleviating Alzheimer's disease; w) preventing, treating or alleviating dementia; x) preventing, treating or alleviating osteoporosis; y) preventing, reducing, eliminating or ameliorating injuries due to Oxidative stress; z) enhancing and/or preserving the stability of HDL from oxidation; aa)enhancing and/or preserving the stability of LDL, VLDL or IDL from oxidation bb)enhancing and/or preserving the stability of triglyceride (TG) from oxidation; cc) exhibiting anti-coagulatant properties; dd)exhibiting anti-proliferative properties; ee)exhibiting immunomodulatory properties; ff) exhibiting angiogenic properties; gg)preventing, treating or alleviating tumour growth; hh)increasing bone mass and/or bone turnover; and ii) enhancing any of the non-lipid related, pleiotropic effects achieved by the= administration of statins, in particular at the cellular and molecular level which comprises administering to a non-human animal, a non-toxic and therapeutically effective amount of one or more compounds having the following formulae: o m r2—(ch2)n —c—o-r b) R2—R , with the proviso that R2 is not linked to R via a linker Y-C0-CH2-CH2-C0-0-, wherein Y is O or NH; c) o o 11 U r2 —c —c -o-r 0 II r3—p—o-r 1 ox 57 e) 545087 o R2 —R< —P—O—R ix f) O o r3 —p —r4 -p —o —r ox ox wherein R is a sterol or stanol moiety, R2 is a cholesterol biosynthesis inhibitor with at least one free and reactive carboxyl group; R3 is a cholesterol biosynthesis inhibitor with at least one free and reactive hydroxyl group; R4 is derived from ascorbic acid, X is either hydrogen or is selected from the group consisting of a biologically acceptable metal, or an alkali earth metal and n=1-5, including all biologically acceptable salts or solvates thereof; wherein R is linked in formulae b), c), d) or f) via oxygen, R2 is linked in formulae b), c), d) orf) via a carboxyl function, and R3is linked in formulae b), c), d) orf) via a hydroxyl group. 29. A method according to claim 28, wherein the compound has the formula a), c), d), e) or f) as defined in claim 28. 30. The method of claim 28 or 29 wherein R2 and R3 are selected from the group consisting of competitive inhibitors of HMG CoA reductase, HMG CoA synthase, squalene synthase, and squalene epoxidase. 31. The method of claim 28 or 29 wherein R2 is either atorvastatin or pravastatin. 32. The method of claim 28 or 29 wherein R3 is either simvastatin or lovastatin. 33. A compound according to claim 1, substantially as herein described or exemplified. 34. A pharmaceutical composition according to claim 18, substantially as herein described or exemplified. 35. A use according to claim 23, substantially as herein described or exemplified. 36. A method according to claim 28, substantially as herein described or exemplified. 58
Applications Claiming Priority (2)
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US61545603A | 2003-07-09 | 2003-07-09 | |
PCT/CA2004/000999 WO2005005453A2 (en) | 2003-07-09 | 2004-07-09 | Novel compounds and compositions comprising sterols and/or stanols and cholesterol biosynthesis inhibitors and use thereof in treating or preventing a variety of diseases and conditions. |
Publications (1)
Publication Number | Publication Date |
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NZ545087A true NZ545087A (en) | 2009-10-30 |
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NZ545087A NZ545087A (en) | 2003-07-09 | 2004-07-09 | Novel compounds and compositions comprising sterols and/or stanols and cholesterol biosynthesis inhibitors and use thereof in treating or preventing a variety of diseases and conditions |
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EP (1) | EP1644399A2 (en) |
JP (1) | JP2007525470A (en) |
KR (1) | KR20060052792A (en) |
CN (1) | CN1832957A (en) |
AU (1) | AU2004255285A1 (en) |
BR (1) | BRPI0412439A (en) |
CA (1) | CA2531836A1 (en) |
MX (1) | MXPA06000326A (en) |
NO (1) | NO20060632L (en) |
NZ (1) | NZ545087A (en) |
PL (1) | PL379516A1 (en) |
RU (1) | RU2006103797A (en) |
WO (1) | WO2005005453A2 (en) |
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KR100886466B1 (en) * | 2006-09-12 | 2009-03-04 | (주)한국씨엔에스팜 | New stigmasterol derivatives or pharmaceutically acceptable salts thereof, process for the preparation thereof and composition comprising the same for inhibiting obesity or for preventing and treating hyperlipidemia |
DE102007005045B4 (en) | 2007-01-26 | 2008-12-18 | Sanofi-Aventis | Phenothiazine derivatives, process for their preparation and their use as medicines |
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DE102007063671A1 (en) | 2007-11-13 | 2009-06-25 | Sanofi-Aventis Deutschland Gmbh | New crystalline diphenylazetidinone hydrates, medicaments containing these compounds and their use |
WO2010003624A2 (en) | 2008-07-09 | 2010-01-14 | Sanofi-Aventis | Heterocyclic compounds, processes for their preparation, medicaments comprising these compounds, and the use thereof |
WO2010068601A1 (en) | 2008-12-08 | 2010-06-17 | Sanofi-Aventis | A crystalline heteroaromatic fluoroglycoside hydrate, processes for making, methods of use and pharmaceutical compositions thereof |
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EP2582709B1 (en) | 2010-06-18 | 2018-01-24 | Sanofi | Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases |
WO2012120057A1 (en) | 2011-03-08 | 2012-09-13 | Sanofi | Novel substituted phenyl-oxathiazine derivatives, method for producing them, drugs containing said compounds and the use thereof |
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US5216015A (en) * | 1991-02-05 | 1993-06-01 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Compounds having hypocholesterolemic properties |
KR100711861B1 (en) * | 1999-06-23 | 2007-04-25 | 포비스 메디-테크 인코포레이티드 | Conjugates of phytosterol or phytostanol with ascorbic acid and use thereof in treating or preventing cardiovascular disease |
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- 2004-07-09 KR KR1020067000470A patent/KR20060052792A/en not_active Application Discontinuation
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NO20060632L (en) | 2006-04-06 |
WO2005005453A2 (en) | 2005-01-20 |
CN1832957A (en) | 2006-09-13 |
PL379516A1 (en) | 2006-10-02 |
RU2006103797A (en) | 2006-07-27 |
AU2004255285A1 (en) | 2005-01-20 |
MXPA06000326A (en) | 2006-03-30 |
WO2005005453A3 (en) | 2005-06-09 |
EP1644399A2 (en) | 2006-04-12 |
BRPI0412439A (en) | 2006-09-05 |
KR20060052792A (en) | 2006-05-19 |
CA2531836A1 (en) | 2005-01-20 |
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