IL93456A - D2 Aphimer of A1- hydroxyvitamin and pharmaceutical preparations containing it - Google Patents
D2 Aphimer of A1- hydroxyvitamin and pharmaceutical preparations containing itInfo
- Publication number
- IL93456A IL93456A IL9345690A IL9345690A IL93456A IL 93456 A IL93456 A IL 93456A IL 9345690 A IL9345690 A IL 9345690A IL 9345690 A IL9345690 A IL 9345690A IL 93456 A IL93456 A IL 93456A
- Authority
- IL
- Israel
- Prior art keywords
- vitamin
- hydroxy
- compound
- epi
- hydroxyvitamin
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- HKXBNHCUPKIYDM-CGMHZMFXSA-N doxercalciferol Chemical class C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C HKXBNHCUPKIYDM-CGMHZMFXSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 35
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000011575 calcium Substances 0.000 abstract description 20
- 230000000694 effects Effects 0.000 abstract description 20
- 229910052791 calcium Inorganic materials 0.000 abstract description 19
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 abstract description 17
- 210000000988 bone and bone Anatomy 0.000 abstract description 15
- 230000004069 differentiation Effects 0.000 abstract description 13
- 230000000968 intestinal effect Effects 0.000 abstract description 7
- 230000004936 stimulating effect Effects 0.000 abstract description 5
- -1 vitamin D2 compound Chemical class 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 3
- 229960002061 ergocalciferol Drugs 0.000 abstract description 3
- 239000011653 vitamin D2 Substances 0.000 abstract description 3
- 230000001939 inductive effect Effects 0.000 abstract description 2
- 230000027425 release of sequestered calcium ion into cytosol Effects 0.000 abstract description 2
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 abstract 1
- 235000001892 vitamin D2 Nutrition 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 229940088594 vitamin Drugs 0.000 description 23
- 239000011782 vitamin Substances 0.000 description 23
- 239000000203 mixture Substances 0.000 description 13
- 239000011710 vitamin D Substances 0.000 description 13
- 229940046008 vitamin d Drugs 0.000 description 13
- 150000003462 sulfoxides Chemical class 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 229930003316 Vitamin D Natural products 0.000 description 9
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 9
- 230000032258 transport Effects 0.000 description 9
- 235000019166 vitamin D Nutrition 0.000 description 9
- 150000003710 vitamin D derivatives Chemical class 0.000 description 9
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 229940093499 ethyl acetate Drugs 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 238000003556 assay Methods 0.000 description 7
- 229930003231 vitamin Natural products 0.000 description 7
- 235000013343 vitamin Nutrition 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical class [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 150000003722 vitamin derivatives Chemical class 0.000 description 6
- MZWRKRWZTKMJOZ-VXKWHMMOSA-N 2-[(2s)-2,3-dimethylbutyl]-4-[3-[(2s)-2,3-dimethylbutyl]-4-methylphenyl]sulfonyl-1-methylbenzene Chemical compound C1=C(C)C(C[C@H](C)C(C)C)=CC(S(=O)(=O)C=2C=C(C[C@H](C)C(C)C)C(C)=CC=2)=C1 MZWRKRWZTKMJOZ-VXKWHMMOSA-N 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229910052786 argon Inorganic materials 0.000 description 4
- 150000002440 hydroxy compounds Chemical class 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 150000003457 sulfones Chemical class 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- MZWRKRWZTKMJOZ-FGZHOGPDSA-N 2-[(2r)-2,3-dimethylbutyl]-4-[3-[(2r)-2,3-dimethylbutyl]-4-methylphenyl]sulfonyl-1-methylbenzene Chemical compound C1=C(C)C(C[C@@H](C)C(C)C)=CC(S(=O)(=O)C=2C=C(C[C@@H](C)C(C)C)C(C)=CC=2)=C1 MZWRKRWZTKMJOZ-FGZHOGPDSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 206010057249 Phagocytosis Diseases 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000024245 cell differentiation Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 235000010755 mineral Nutrition 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000008782 phagocytosis Effects 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000018678 bone mineralization Effects 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 230000001483 mobilizing effect Effects 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 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 description 1
- RQOCXCFLRBRBCS-UHFFFAOYSA-N (22E)-cholesta-5,7,22-trien-3beta-ol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CCC(C)C)CCC33)C)C3=CC=C21 RQOCXCFLRBRBCS-UHFFFAOYSA-N 0.000 description 1
- NQICGNSARVCSGJ-JTTVCCKGSA-N (5-methyl-2-propan-2-ylcyclohexyl) 4-methylbenzenesulfinate Chemical compound CC(C)C1CCC(C)CC1O[S@@](=O)C1=CC=C(C)C=C1 NQICGNSARVCSGJ-JTTVCCKGSA-N 0.000 description 1
- YKZYRVIFGPGJJI-UHFFFAOYSA-N 1-[1-[2,3-dimethyl-1-(4-methylphenyl)butyl]sulfinyl-2,3-dimethylbutyl]-4-methylbenzene Chemical class C=1C=C(C)C=CC=1C(C(C)C(C)C)S(=O)C(C(C)C(C)C)C1=CC=C(C)C=C1 YKZYRVIFGPGJJI-UHFFFAOYSA-N 0.000 description 1
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 1
- SXSWMAUXEHKFGX-UHFFFAOYSA-N 2,3-dimethylbutan-1-ol Chemical compound CC(C)C(C)CO SXSWMAUXEHKFGX-UHFFFAOYSA-N 0.000 description 1
- MPHUAKIJAGYUEQ-VXKWHMMOSA-N 2-[(2s)-2,3-dimethylbutyl]-4-[3-[(2s)-2,3-dimethylbutyl]-4-methylphenyl]sulfinyl-1-methylbenzene Chemical compound C1=C(C)C(C[C@H](C)C(C)C)=CC(S(=O)C=2C=C(C[C@H](C)C(C)C)C(C)=CC=2)=C1 MPHUAKIJAGYUEQ-VXKWHMMOSA-N 0.000 description 1
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-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
- 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 description 1
- 229910000497 Amalgam Inorganic materials 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 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 description 1
- 238000003747 Grignard reaction Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010031240 Osteodystrophy Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000000125 calcaemic effect Effects 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 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 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000031891 intestinal absorption Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- JPXMTWWFLBLUCD-UHFFFAOYSA-N nitro blue tetrazolium(2+) Chemical compound COC1=CC(C=2C=C(OC)C(=CC=2)[N+]=2N(N=C(N=2)C=2C=CC=CC=2)C=2C=CC(=CC=2)[N+]([O-])=O)=CC=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=C([N+]([O-])=O)C=C1 JPXMTWWFLBLUCD-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000004807 phenyl sulfones Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 210000004765 promyelocyte Anatomy 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 229910001023 sodium amalgam Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 150000003431 steroids Chemical group 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C401/00—Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
-
- 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
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P3/02—Nutrients, e.g. vitamins, minerals
-
- 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
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Nutrition Science (AREA)
- Endocrinology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/321,254 US4973584A (en) | 1989-03-09 | 1989-03-09 | Novel 1α-hydroxyvitamin D2 epimer and derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL93456A0 IL93456A0 (en) | 1990-11-29 |
| IL93456A true IL93456A (en) | 1994-02-27 |
Family
ID=23249837
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9345690A IL93456A (en) | 1989-03-09 | 1990-02-20 | D2 Aphimer of A1- hydroxyvitamin and pharmaceutical preparations containing it |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4973584A (de) |
| EP (1) | EP0386793B1 (de) |
| JP (1) | JPH0737443B2 (de) |
| KR (1) | KR950005776B1 (de) |
| AT (1) | ATE90342T1 (de) |
| AU (1) | AU631618B2 (de) |
| CA (1) | CA1335105C (de) |
| DE (1) | DE69001839T2 (de) |
| DK (1) | DK0386793T3 (de) |
| ES (1) | ES2055193T3 (de) |
| HU (1) | HU207040B (de) |
| IL (1) | IL93456A (de) |
| NZ (1) | NZ232735A (de) |
| RU (1) | RU2065851C1 (de) |
| WO (1) | WO1990010619A1 (de) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5260290A (en) * | 1990-02-14 | 1993-11-09 | Wisconsin Alumni Research Foundation | Homologated vitamin D2 compounds and the corresponding 1α-hydroxylated derivatives |
| US5030772A (en) * | 1990-02-14 | 1991-07-09 | Deluca Hector F | Process for preparing vitamin D2 compounds and the corresponding 1 α-hydroxylated derivatives |
| US5756783A (en) * | 1990-09-21 | 1998-05-26 | Bone Care International, Inc. | 1α-Hydroxy-24-EPI-vitamin D4 |
| US20040009958A1 (en) * | 1991-01-08 | 2004-01-15 | Bone Care International, Inc. | Methods for preparation and use of 1alpha,24(S)-dihydroxyvitamin D2 |
| US6251883B1 (en) | 1991-01-08 | 2001-06-26 | Bone Care International, Inc. | Methods for preparation and use of 1α,24(S)-dihydroxy vitamin D2 |
| US6538037B2 (en) | 1991-01-08 | 2003-03-25 | Bone Care International, Inc. | Methods for preparation and use of 1α,24(S)-dihydroxyvitamin D2 |
| US5789397A (en) * | 1991-01-08 | 1998-08-04 | Bone Care International, Inc. | Methods for preparation and use of 1A,24(S)-dihydroxy vitamin D2 |
| US5182396A (en) * | 1991-03-29 | 1993-01-26 | Nisshin Flour Milling Co., Ltd. | 1-hydroxyvitamin d derivatives |
| AU656829B2 (en) * | 1991-12-26 | 1995-02-16 | Wisconsin Alumni Research Foundation | 26, 27-dimethylene-1 alpha, 25-dihydroxyvitamin D2 and 26,27-dihydroxyvitamin D2 and methods for preparing same |
| AU682817B2 (en) * | 1992-01-29 | 1997-10-23 | Bone Care International, Inc. | 1alpha-hydroxy-24-(epi)-vitamin D4 |
| US5194431A (en) * | 1992-07-08 | 1993-03-16 | Wisconsin Alumni Research Foundation | 24-cyclopropane vitamin D derivatives |
| DE69325253T2 (de) * | 1992-08-28 | 1999-12-02 | Bone Care International Inc., Madison | 1alpha,24(s)-dihydroxy vitamin d2, seine synthese und verwendung |
| TW267161B (de) * | 1992-11-20 | 1996-01-01 | Hoffmann La Roche | |
| JPH0753384A (ja) * | 1993-07-13 | 1995-02-28 | Wisconsin Alumni Res Found | ２４−エピ−１α−ヒドロキシビタミンＤ２ を含んでなる骨粗鬆症治療剤 |
| US5565589A (en) * | 1993-11-03 | 1996-10-15 | Wisconsin Alumni Research Foundation | 17-formyl-5,6-trans-vitamin D compounds |
| US5373004A (en) * | 1993-11-24 | 1994-12-13 | Wisconsin Alumni Research Foundation | 26,28-methylene-1α, 25-dihydroxyvitamin D2 compounds |
| US5661140A (en) * | 1994-11-21 | 1997-08-26 | Wisconsin Alumni Research Foundation | 18-nor-vitamin D compounds |
| US5716946A (en) * | 1996-02-13 | 1998-02-10 | Wisconsin Alumni Research Foundation | Multiple sclerosis treatment |
| US6416737B1 (en) | 1998-11-19 | 2002-07-09 | Board Of Trustees Of The University Of Arkansas | Increasing bone strength with selected bisphosphonates |
| WO2000059513A1 (en) * | 1999-04-01 | 2000-10-12 | Johns Hopkins University | NON-CALCEMIC, ANTIPROLIFERATIVE, TRANSCRIPTIONALLY ACTIVE SULFUR-CONTAINING ANALOGS OF 1α, 25-DIHYDROXY VITAMIN D¿3? |
| US6479474B2 (en) | 1999-07-08 | 2002-11-12 | Wisconsin Alumni Research Foundation | Dietary calcium as a supplement to vitamin D compound treatment of multiple sclerosis |
| ATE428692T1 (de) * | 2001-08-22 | 2009-05-15 | Univ Johns Hopkins | 24-schwefel-substituierte 1-alpha-25-dihydroxy- vitamin-d3-analogen |
| WO2003106411A1 (en) | 2002-06-13 | 2003-12-24 | Johns Hopkins University | 24-sulfoximine vitamin d3 compounds |
| WO2004054968A2 (en) | 2002-12-18 | 2004-07-01 | Johns Hopkins University | 25-so2-substituted analogs of 1alpha, 25-dihydroxyvitamin d3 (calcitriol) |
| JP5009617B2 (ja) * | 2003-08-20 | 2012-08-22 | ウイスコンシン アラムニ リサーチ ファンデーション | ２−メチレン−１９−ノル−ビタミンｄ２化合物 |
| AU2010208323B2 (en) | 2009-01-27 | 2016-03-10 | Berg Llc | Vitamin D3 and analogs thereof for alleviating side effects associated with chemotherapy |
| EP2464357B1 (de) | 2009-08-14 | 2019-05-22 | Berg LLC | Vitamin d3 und analoge davon zur behandlung von alopezie |
| SG10201709894RA (en) | 2013-05-29 | 2018-01-30 | Berg Llc | Preventing or mitigating chemotherapy induced alopecia using vitamin d |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3880894A (en) * | 1974-05-24 | 1975-04-29 | Wisconsin Alumni Res Found | 1,25-Dihydroxyergocalciferol |
| US3907843A (en) * | 1974-06-14 | 1975-09-23 | Wisconsin Alumni Res Found | 1{60 -Hydroxyergocalciferol and processes for preparing same |
| NL193245C (nl) * | 1983-05-09 | 1999-04-02 | Wisconsin Alumni Res Found | Aan 1Ó,25-dihydroxyvitamine D2 verwante verbinding en farmaceutisch preparaat met een het calciummetabolisme regulerende werking dat een dergelijke verbinding bevat. |
| US4769181A (en) * | 1983-11-07 | 1988-09-06 | Wisconsin Alumni Research Foundation | 1,25-dihydroxyvitamin D2 compounds |
| US4588528A (en) * | 1984-05-31 | 1986-05-13 | Wisconsin Alumni Research Foundation | 1,24-dihydroxy-Δ22 -vitamin D3 and process for preparing same |
| US4612308A (en) * | 1984-11-29 | 1986-09-16 | Hoffmann-La Roche Inc. | 25,26-Dehydro-1α,23(S,R)-dihydroxycholecalciferol and its epimers |
| US4717721A (en) * | 1985-05-30 | 1988-01-05 | Howard W. Bremer | Sidechain homo-vitamin D compounds with preferential anti-cancer activity |
-
1989
- 1989-03-09 US US07/321,254 patent/US4973584A/en not_active Expired - Lifetime
- 1989-09-22 CA CA000612518A patent/CA1335105C/en not_active Expired - Fee Related
-
1990
- 1990-02-16 WO PCT/US1990/000952 patent/WO1990010619A1/en not_active Ceased
- 1990-02-16 AU AU51925/90A patent/AU631618B2/en not_active Ceased
- 1990-02-16 RU SU904831932A patent/RU2065851C1/ru active
- 1990-02-16 HU HU8822A patent/HU207040B/hu not_active IP Right Cessation
- 1990-02-16 JP JP2504397A patent/JPH0737443B2/ja not_active Expired - Lifetime
- 1990-02-16 KR KR1019900702409A patent/KR950005776B1/ko not_active Expired - Fee Related
- 1990-02-20 IL IL9345690A patent/IL93456A/en not_active IP Right Cessation
- 1990-02-28 NZ NZ232735A patent/NZ232735A/en unknown
- 1990-03-09 AT AT90104564T patent/ATE90342T1/de not_active IP Right Cessation
- 1990-03-09 DE DE9090104564T patent/DE69001839T2/de not_active Expired - Fee Related
- 1990-03-09 DK DK90104564.1T patent/DK0386793T3/da active
- 1990-03-09 EP EP90104564A patent/EP0386793B1/de not_active Expired - Lifetime
- 1990-03-09 ES ES90104564T patent/ES2055193T3/es not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| US4973584A (en) | 1990-11-27 |
| HU207040B (en) | 1993-03-01 |
| DK0386793T3 (da) | 1993-08-02 |
| HU902288D0 (en) | 1991-07-29 |
| JPH0737443B2 (ja) | 1995-04-26 |
| JPH03504508A (ja) | 1991-10-03 |
| DE69001839D1 (de) | 1993-07-15 |
| AU631618B2 (en) | 1992-12-03 |
| EP0386793A1 (de) | 1990-09-12 |
| EP0386793B1 (de) | 1993-06-09 |
| ATE90342T1 (de) | 1993-06-15 |
| DE69001839T2 (de) | 1993-09-16 |
| ES2055193T3 (es) | 1994-08-16 |
| KR950005776B1 (ko) | 1995-05-30 |
| IL93456A0 (en) | 1990-11-29 |
| KR920700201A (ko) | 1992-02-19 |
| NZ232735A (en) | 1992-07-28 |
| RU2065851C1 (ru) | 1996-08-27 |
| WO1990010619A1 (en) | 1990-09-20 |
| CA1335105C (en) | 1995-04-04 |
| AU5192590A (en) | 1990-10-09 |
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| Date | Code | Title | Description |
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| KB | Patent renewed | ||
| KB | Patent renewed | ||
| RH1 | Patent not in force |