JPS58126862A - １−ヒドロキシル化ビタミンｄ化合物の製法 - Google Patents
１−ヒドロキシル化ビタミンｄ化合物の製法Info
- Publication number
- JPS58126862A JPS58126862A JP19195682A JP19195682A JPS58126862A JP S58126862 A JPS58126862 A JP S58126862A JP 19195682 A JP19195682 A JP 19195682A JP 19195682 A JP19195682 A JP 19195682A JP S58126862 A JPS58126862 A JP S58126862A
- Authority
- JP
- Japan
- Prior art keywords
- vitamin
- group
- compound
- selenite
- hydroxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims description 33
- 238000004519 manufacturing process Methods 0.000 title description 11
- WIGIZIANZCJQQY-UHFFFAOYSA-N 4-ethyl-3-methyl-N-[2-[4-[[[(4-methylcyclohexyl)amino]-oxomethyl]sulfamoyl]phenyl]ethyl]-5-oxo-2H-pyrrole-1-carboxamide Chemical class O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCC(C)CC2)C=C1 WIGIZIANZCJQQY-UHFFFAOYSA-N 0.000 title 1
- -1 vitamin D compounds Chemical class 0.000 claims description 48
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 39
- 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 claims description 35
- 239000011710 vitamin D Substances 0.000 claims description 35
- 229940046008 vitamin d Drugs 0.000 claims description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 33
- 229930003316 Vitamin D Natural products 0.000 claims description 32
- 235000019166 vitamin D Nutrition 0.000 claims description 32
- 229940082569 selenite Drugs 0.000 claims description 26
- MCAHWIHFGHIESP-UHFFFAOYSA-L selenite(2-) Chemical compound [O-][Se]([O-])=O MCAHWIHFGHIESP-UHFFFAOYSA-L 0.000 claims description 26
- 238000007254 oxidation reaction Methods 0.000 claims description 25
- 230000003647 oxidation Effects 0.000 claims description 18
- 239000007800 oxidant agent Substances 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 239000007858 starting material Substances 0.000 claims description 11
- 239000011541 reaction mixture Substances 0.000 claims description 10
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- 238000005805 hydroxylation reaction Methods 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 230000001590 oxidative effect Effects 0.000 claims description 6
- 239000000376 reactant Substances 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000011065 in-situ storage Methods 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000000468 ketone group Chemical group 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 2
- 125000003700 epoxy group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 150000004965 peroxy acids Chemical class 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 239000000203 mixture Substances 0.000 description 38
- 239000000243 solution Substances 0.000 description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000006317 isomerization reaction Methods 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 229940088594 vitamin Drugs 0.000 description 14
- 239000011782 vitamin Substances 0.000 description 14
- 150000003722 vitamin derivatives Chemical class 0.000 description 14
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 12
- 229930003231 vitamin Natural products 0.000 description 11
- 235000013343 vitamin Nutrition 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- OFHCOWSQAMBJIW-AVJTYSNKSA-N alfacalcidol Chemical class C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C OFHCOWSQAMBJIW-AVJTYSNKSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 229960002061 ergocalciferol Drugs 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 238000010626 work up procedure Methods 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
- 239000011653 vitamin D2 Substances 0.000 description 6
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 235000001892 vitamin D2 Nutrition 0.000 description 5
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound 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)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 5
- 208000013038 Hypocalcemia Diseases 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
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000000705 hypocalcaemia Effects 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- WAZPLXZGZWWXDQ-UHFFFAOYSA-N 4-methyl-4-oxidomorpholin-4-ium;hydrate Chemical compound O.C[N+]1([O-])CCOCC1 WAZPLXZGZWWXDQ-UHFFFAOYSA-N 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 3
- 208000020084 Bone disease Diseases 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000004020 conductor Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000010409 thin film Substances 0.000 description 3
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 3
- 235000005282 vitamin D3 Nutrition 0.000 description 3
- 239000011647 vitamin D3 Substances 0.000 description 3
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound 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-YRZJJWOYSA-N 0.000 description 3
- 229940021056 vitamin d3 Drugs 0.000 description 3
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 101001081176 Homo sapiens Hyaluronan mediated motility receptor Proteins 0.000 description 2
- 102100027735 Hyaluronan mediated motility receptor Human genes 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000746 allylic group Chemical group 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 2
- UEJBTVZPRCSFBM-UHFFFAOYSA-N diethyl selenite Chemical compound CCO[Se](=O)OCC UEJBTVZPRCSFBM-UHFFFAOYSA-N 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- YWWZCHLUQSHMCL-UHFFFAOYSA-N diphenyl diselenide Chemical compound C=1C=CC=CC=1[Se][Se]C1=CC=CC=C1 YWWZCHLUQSHMCL-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 229960003750 ethyl chloride Drugs 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000011491 glass wool Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 150000002432 hydroperoxides Chemical class 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 238000007699 photoisomerization reaction Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 208000007442 rickets Diseases 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- 125000005490 tosylate group Chemical class 0.000 description 2
- 150000005671 trienes Chemical class 0.000 description 2
- RMDJVOZETBHEAR-LQYWTLTGSA-N vitamin D5 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CC[C@@H](CC)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C RMDJVOZETBHEAR-LQYWTLTGSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- PLSKUXASMLOIHH-UHFFFAOYSA-N 1,3,2$l^{4}-dioxaselenolane 2-oxide Chemical compound O=[Se]1OCCO1 PLSKUXASMLOIHH-UHFFFAOYSA-N 0.000 description 1
- VEPOHXYIFQMVHW-XOZOLZJESA-N 2,3-dihydroxybutanedioic acid (2S,3S)-3,4-dimethyl-2-phenylmorpholine Chemical compound OC(C(O)C(O)=O)C(O)=O.C[C@H]1[C@@H](OCCN1C)c1ccccc1 VEPOHXYIFQMVHW-XOZOLZJESA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- QYSXJUFSXHHAJI-FVUVGDFOSA-N 5,6-trans-vitamin D3 Chemical compound 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-FVUVGDFOSA-N 0.000 description 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000013725 Chronic Kidney Disease-Mineral and Bone disease Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 208000029663 Hypophosphatemia Diseases 0.000 description 1
- 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 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 1
- 241001474791 Proboscis Species 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 206010041969 Steatorrhoea Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 125000005333 aroyloxy group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000002826 coolant Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 150000001993 dienes Chemical class 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- NTEFHFJOCXLHIX-UHFFFAOYSA-N dimethyl selenite Chemical compound CO[Se](=O)OC NTEFHFJOCXLHIX-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- MCAHWIHFGHIESP-UHFFFAOYSA-M hydrogenselenite Chemical compound O[Se]([O-])=O MCAHWIHFGHIESP-UHFFFAOYSA-M 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 210000003127 knee Anatomy 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000004971 nitroalkyl group Chemical group 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 208000005368 osteomalacia Diseases 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 239000005297 pyrex Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 201000006409 renal osteodystrophy Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 238000006884 silylation reaction Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 208000001162 steatorrhea Diseases 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical class CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000003698 tetramethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000005979 thermal decomposition reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- PNVUZMNHWBDJQY-UHFFFAOYSA-N trioxidanylmethane Chemical compound COOO PNVUZMNHWBDJQY-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8133021 | 1981-11-02 | ||
| GB8133019 | 1981-11-02 | ||
| GB8133019 | 1981-11-02 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58126862A true JPS58126862A (ja) | 1983-07-28 |
| JPH0353299B2 JPH0353299B2 (enrdf_load_stackoverflow) | 1991-08-14 |
Family
ID=10525577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP19195682A Granted JPS58126862A (ja) | 1981-11-02 | 1982-11-02 | １−ヒドロキシル化ビタミンｄ化合物の製法 |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS58126862A (enrdf_load_stackoverflow) |
| ZA (1) | ZA828012B (enrdf_load_stackoverflow) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6045516A (ja) * | 1983-08-02 | 1985-03-12 | Kureha Chem Ind Co Ltd | １α―ヒドロキシビタミンＤ３類を含有することを特徴とする抗炎症解熱鎮痛剤 |
| JPS60120812A (ja) * | 1983-12-02 | 1985-06-28 | Teijin Ltd | 糖尿病性骨減少症治療剤 |
| JP2004504295A (ja) * | 2000-07-18 | 2004-02-12 | ボーン ケア インターナショナル インコーポレイテッド | 安定化１α−ヒドロキシビタミンＤ |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55105662A (en) * | 1978-11-07 | 1980-08-13 | Res Inst Medicine Chem | Manufacture of 11hydroxlated vitamin d |
-
1982
- 1982-11-02 JP JP19195682A patent/JPS58126862A/ja active Granted
- 1982-11-02 ZA ZA828012A patent/ZA828012B/xx unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS55105662A (en) * | 1978-11-07 | 1980-08-13 | Res Inst Medicine Chem | Manufacture of 11hydroxlated vitamin d |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6045516A (ja) * | 1983-08-02 | 1985-03-12 | Kureha Chem Ind Co Ltd | １α―ヒドロキシビタミンＤ３類を含有することを特徴とする抗炎症解熱鎮痛剤 |
| JPS60120812A (ja) * | 1983-12-02 | 1985-06-28 | Teijin Ltd | 糖尿病性骨減少症治療剤 |
| JP2004504295A (ja) * | 2000-07-18 | 2004-02-12 | ボーン ケア インターナショナル インコーポレイテッド | 安定化１α−ヒドロキシビタミンＤ |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0353299B2 (enrdf_load_stackoverflow) | 1991-08-14 |
| ZA828012B (en) | 1983-09-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP3494637B2 (ja) | １９−ノル−ビタミンｄ化合物の中間体の製造方法 | |
| JPH02163A (ja) | 新規化合物およびその製法 | |
| EP0078705B1 (en) | Process for the preparation of 1-hydroxylated vitamin d compounds | |
| JPS5854160B2 (ja) | １α，３β−ジヒドロキシステロイド−５−エンまたはその誘導体の製造方法 | |
| JPH0742305B2 (ja) | ２５，２６，２７−トリノルコレステロール化合物 | |
| JPS58126862A (ja) | １−ヒドロキシル化ビタミンｄ化合物の製法 | |
| JPS5823660A (ja) | １α―ヒドロキシビタミンＤまたは１α―ヒドロキシ―プレビタミンＤ化合物の製造方法 | |
| DK158991B (da) | Cholestadienderivater, der kan anvendes som mellemprodukter til brug ved fremstillingen af homovitamin-d3-derivater | |
| CZ286090B6 (cs) | Způsob výroby derivátů vitaminu D a aldehydický adukt použitelný jako meziprodukt | |
| EP0045524A1 (en) | 22-Arylsulfonyl-24,25-dihydroxycholestanes and process for preparing the same | |
| JPH0489473A (ja) | １α―ヒドロキシタキステロール誘導体の製造方法 | |
| JPH05208995A (ja) | ビタミンｄ誘導体のための中間体および製造方法 | |
| JP3483155B2 (ja) | １α，２５−ジヒドロキシビタミンＤ４およびＤ７の製造法 | |
| JP3105973B2 (ja) | 活性型ビタミンｄ誘導体の製造法 | |
| JP2818493B2 (ja) | ２５−ヒドロキシビタミンＤ２ 化合物および対応する１α−ヒドロキシル化誘導体の製造方法 | |
| JP2750170B2 (ja) | ステロイド誘導体の製造法 | |
| JPH05339230A (ja) | 活性型ビタミンｄ２及びその誘導体の製造法 | |
| JPH07309891A (ja) | ステロイド誘導体の製造法 | |
| WO2006052066A1 (en) | Process for preparing 1-alpha-hydroxycholecalciferol derivatives | |
| JP2683395B2 (ja) | ステロイド誘導体 | |
| JPS63264452A (ja) | フッ素化ビタミンｄ↓３誘導体 | |
| JPS58216179A (ja) | ７，８−エポキシ化ビタミンｄ↓３誘導体 | |
| JPS6028986A (ja) | ステロイドの製造法 | |
| NO180537B (no) | Fremgangsmåte for fremstilling av vitamin D2-forbindelser og de tilsvarende -hydroksylerte derivater | |
| JPH0873425A (ja) | フッ素化ビタミンｄ誘導体および製造方法 |