IL130484A - History of -16N-Vitamin-D - Google Patents
History of -16N-Vitamin-DInfo
- Publication number
- IL130484A IL130484A IL13048497A IL13048497A IL130484A IL 130484 A IL130484 A IL 130484A IL 13048497 A IL13048497 A IL 13048497A IL 13048497 A IL13048497 A IL 13048497A IL 130484 A IL130484 A IL 130484A
- Authority
- IL
- Israel
- Prior art keywords
- hydroxy
- dihydroxy
- ethyl
- brs
- tetraene
- Prior art date
Links
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 63
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 42
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 34
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 27
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 150000003710 vitamin D derivatives Chemical class 0.000 claims abstract description 22
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
- 125000003118 aryl group Chemical group 0.000 claims abstract description 16
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 15
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 15
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 239000001301 oxygen Substances 0.000 claims abstract description 11
- -1 3-hydroxy-3-methylbutyl group Chemical group 0.000 claims description 503
- 150000001875 compounds Chemical class 0.000 claims description 208
- 238000000034 method Methods 0.000 claims description 91
- 125000006239 protecting group Chemical group 0.000 claims description 17
- 239000008177 pharmaceutical agent Substances 0.000 claims description 8
- 238000006317 isomerization reaction Methods 0.000 claims description 7
- 238000010511 deprotection reaction Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 501
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 366
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 332
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 293
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 286
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 166
- 238000012746 preparative thin layer chromatography Methods 0.000 description 148
- 239000000243 solution Substances 0.000 description 139
- 238000002360 preparation method Methods 0.000 description 118
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 114
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 112
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 108
- 239000012230 colorless oil Substances 0.000 description 103
- 238000005481 NMR spectroscopy Methods 0.000 description 84
- 238000001819 mass spectrum Methods 0.000 description 79
- 238000006243 chemical reaction Methods 0.000 description 77
- 238000010992 reflux Methods 0.000 description 56
- 238000010438 heat treatment Methods 0.000 description 49
- 239000002904 solvent Substances 0.000 description 47
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 28
- 239000012267 brine Substances 0.000 description 22
- 239000011259 mixed solution Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- 229910001868 water Inorganic materials 0.000 description 20
- 239000000047 product Substances 0.000 description 18
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 17
- 239000012312 sodium hydride Substances 0.000 description 17
- 229910000104 sodium hydride Inorganic materials 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- VFTFKUDGYRBSAL-UHFFFAOYSA-N 15-crown-5 Chemical compound C1COCCOCCOCCOCCO1 VFTFKUDGYRBSAL-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 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)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 14
- 150000003704 vitamin D3 derivatives Chemical class 0.000 description 14
- 238000005804 alkylation reaction Methods 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 9
- 230000004069 differentiation Effects 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 239000011575 calcium Substances 0.000 description 8
- 229910052791 calcium Inorganic materials 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 230000001939 inductive effect Effects 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- KOSYAAIZOGNATQ-UHFFFAOYSA-N o-phenyl chloromethanethioate Chemical compound ClC(=S)OC1=CC=CC=C1 KOSYAAIZOGNATQ-UHFFFAOYSA-N 0.000 description 7
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 102000009310 vitamin D receptors Human genes 0.000 description 7
- 108050000156 vitamin D receptors Proteins 0.000 description 7
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
- 208000037147 Hypercalcaemia Diseases 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 description 6
- 238000011156 evaluation Methods 0.000 description 6
- 230000000148 hypercalcaemia Effects 0.000 description 6
- 208000030915 hypercalcemia disease Diseases 0.000 description 6
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
- 238000010626 work up procedure Methods 0.000 description 6
- GNRLXJIJULMSKF-KVVMQPAJSA-N (1R)-2-[tert-butyl(dimethyl)silyl]oxy-1-[(9S,10R,13S,14S)-10,13-dimethyl-2,3,4,9,11,12,14,15-octahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanol Chemical compound [Si](C)(C)(C(C)(C)C)OC[C@@H](C1=CC[C@H]2C3=CC=C4CCCC[C@]4(C)[C@H]3CC[C@]12C)O GNRLXJIJULMSKF-KVVMQPAJSA-N 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- KCERYUSEDXNNHR-IDNYGZCWSA-N (1s)-1-[(1s,3r,9s,10r,13s,14s)-1,3-bis[[tert-butyl(dimethyl)silyl]oxy]-10,13-dimethyl-2,3,4,9,11,12,14,15-octahydro-1h-cyclopenta[a]phenanthren-17-yl]ethanol Chemical compound C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]2(C)[C@@H](CC[C@@]3(C([C@@H](O)C)=CC[C@H]33)C)C3=CC=C21 KCERYUSEDXNNHR-IDNYGZCWSA-N 0.000 description 4
- ACWCGDGCBASRKT-UHFFFAOYSA-N 1-bromo-3-ethylpentan-3-ol Chemical compound CCC(O)(CC)CCBr ACWCGDGCBASRKT-UHFFFAOYSA-N 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
- AQOUWWUQSJUIOL-UHFFFAOYSA-N 2-pentan-3-yloxirane Chemical compound CCC(CC)C1CO1 AQOUWWUQSJUIOL-UHFFFAOYSA-N 0.000 description 4
- RBFVGQWGOARJRU-UHFFFAOYSA-N 4-bromo-2-methylbutan-2-ol Chemical compound CC(C)(O)CCBr RBFVGQWGOARJRU-UHFFFAOYSA-N 0.000 description 4
- YDZBUQJQTJIIBL-UHFFFAOYSA-N 6-bromo-2-methylhexan-2-ol Chemical compound CC(C)(O)CCCCBr YDZBUQJQTJIIBL-UHFFFAOYSA-N 0.000 description 4
- XWPXCICGZJYFBC-UHFFFAOYSA-N 6-bromo-3-ethylhexan-3-ol Chemical compound CCC(O)(CC)CCCBr XWPXCICGZJYFBC-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- JIHYVJVUTYJQNX-KTKRTIGZSA-N [(z)-5-bromo-2-methylpent-3-en-2-yl]oxy-triethylsilane Chemical compound CC[Si](CC)(CC)OC(C)(C)\C=C/CBr JIHYVJVUTYJQNX-KTKRTIGZSA-N 0.000 description 4
- PIYGGTMRVZMESL-QXMHVHEDSA-N [(z)-6-bromo-3-ethylhex-4-en-3-yl]oxy-triethylsilane Chemical compound CC[Si](CC)(CC)OC(CC)(CC)\C=C/CBr PIYGGTMRVZMESL-QXMHVHEDSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 239000003435 antirheumatic agent Substances 0.000 description 4
- YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 4
- 230000000121 hypercalcemic effect Effects 0.000 description 4
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- GNRLXJIJULMSKF-DJXHULFLSA-N (1S)-2-[tert-butyl(dimethyl)silyl]oxy-1-[(9S,10R,13S,14S)-10,13-dimethyl-2,3,4,9,11,12,14,15-octahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanol Chemical compound C(C)(C)(C)[Si](OC[C@H](C1=CC[C@H]2C3=CC=C4CCCC[C@]4(C)[C@H]3CC[C@]12C)O)(C)C GNRLXJIJULMSKF-DJXHULFLSA-N 0.000 description 3
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 3
- NGHUFOGBPHDTHY-ONEGZZNKSA-N (e)-5-bromo-2-methylpent-3-en-2-ol Chemical compound CC(C)(O)\C=C\CBr NGHUFOGBPHDTHY-ONEGZZNKSA-N 0.000 description 3
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
- ISULLEUFOQSBGY-UHFFFAOYSA-N 4-phenyl-1,2,4-triazole-3,5-dione Chemical compound O=C1N=NC(=O)N1C1=CC=CC=C1 ISULLEUFOQSBGY-UHFFFAOYSA-N 0.000 description 3
- JPICDYJACXLENM-DNZWLJDLSA-N C([C@H]1C=2[C@@H]([C@]3(CCCCC3=CC=2)C)CC[C@@]11C)C=C1CCSC(=O)OC1=CC=CC=C1 Chemical compound C([C@H]1C=2[C@@H]([C@]3(CCCCC3=CC=2)C)CC[C@@]11C)C=C1CCSC(=O)OC1=CC=CC=C1 JPICDYJACXLENM-DNZWLJDLSA-N 0.000 description 3
- 101150041968 CDC13 gene Proteins 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- RCBVKBFIWMOMHF-UHFFFAOYSA-L hydroxy-(hydroxy(dioxo)chromio)oxy-dioxochromium;pyridine Chemical compound C1=CC=NC=C1.C1=CC=NC=C1.O[Cr](=O)(=O)O[Cr](O)(=O)=O RCBVKBFIWMOMHF-UHFFFAOYSA-L 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052987 metal hydride Inorganic materials 0.000 description 3
- 150000004681 metal hydrides Chemical class 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 150000002924 oxiranes Chemical class 0.000 description 3
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 3
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
- 229910000105 potassium hydride Inorganic materials 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 125000005415 substituted alkoxy group Chemical group 0.000 description 3
- 125000003107 substituted aryl group Chemical group 0.000 description 3
- REYZXWIIUPKFTI-YFKPBYRVSA-N (2r)-2-propan-2-yloxirane Chemical compound CC(C)[C@@H]1CO1 REYZXWIIUPKFTI-YFKPBYRVSA-N 0.000 description 2
- REYZXWIIUPKFTI-RXMQYKEDSA-N (2s)-2-propan-2-yloxirane Chemical compound CC(C)[C@H]1CO1 REYZXWIIUPKFTI-RXMQYKEDSA-N 0.000 description 2
- KXKDZLRTIFHOHW-UHFFFAOYSA-N (5-methyl-2-propan-2-ylcyclohexyl) 5-hydroxy-1,3-oxathiolane-2-carboxylate Chemical compound CC(C)C1CCC(C)CC1OC(=O)C1SCC(O)O1 KXKDZLRTIFHOHW-UHFFFAOYSA-N 0.000 description 2
- RDJOJYOGHDUYHJ-AATRIKPKSA-N (e)-6-bromo-3-ethylhex-4-en-3-ol Chemical compound CCC(O)(CC)\C=C\CBr RDJOJYOGHDUYHJ-AATRIKPKSA-N 0.000 description 2
- QPXDKQBBJCTNOY-UHFFFAOYSA-N 1,10-phenanthrolin-10-ium;chloride Chemical compound Cl.C1=CN=C2C3=NC=CC=C3C=CC2=C1 QPXDKQBBJCTNOY-UHFFFAOYSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- GELKGHVAFRCJNA-UHFFFAOYSA-N 2,2-Dimethyloxirane Chemical compound CC1(C)CO1 GELKGHVAFRCJNA-UHFFFAOYSA-N 0.000 description 2
- OVKYVUFYOFPYNK-UHFFFAOYSA-N 2,2-diethyloxirane Chemical compound CCC1(CC)CO1 OVKYVUFYOFPYNK-UHFFFAOYSA-N 0.000 description 2
- UWKQJZCTQGMHKD-UHFFFAOYSA-N 2,6-di-tert-butylpyridine Chemical compound CC(C)(C)C1=CC=CC(C(C)(C)C)=N1 UWKQJZCTQGMHKD-UHFFFAOYSA-N 0.000 description 2
- HVHZEKKZMFRULH-UHFFFAOYSA-N 2,6-ditert-butyl-4-methylpyridine Chemical compound CC1=CC(C(C)(C)C)=NC(C(C)(C)C)=C1 HVHZEKKZMFRULH-UHFFFAOYSA-N 0.000 description 2
- KLNAKPRPVCQFAW-UHFFFAOYSA-N 3-(bromomethyl)-2,2-dimethyloxirane Chemical compound CC1(C)OC1CBr KLNAKPRPVCQFAW-UHFFFAOYSA-N 0.000 description 2
- 125000004337 3-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- SETCXRSLHABWNW-UHFFFAOYSA-N 5-bromo-2-methylpent-3-yn-2-ol Chemical compound CC(C)(O)C#CCBr SETCXRSLHABWNW-UHFFFAOYSA-N 0.000 description 2
- URXHMYXECNIWNJ-UHFFFAOYSA-N 6-bromo-3-ethylhex-4-yn-3-ol Chemical compound CCC(O)(CC)C#CCBr URXHMYXECNIWNJ-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- HDEOQBUMSRTDBE-XSDIEEQYSA-N CCC1=CC[C@H]2C3=CC=C4CCCC[C@]4(C)[C@H]3CC[C@]12C Chemical compound CCC1=CC[C@H]2C3=CC=C4CCCC[C@]4(C)[C@H]3CC[C@]12C HDEOQBUMSRTDBE-XSDIEEQYSA-N 0.000 description 2
- 108010052832 Cytochromes Proteins 0.000 description 2
- 102000018832 Cytochromes Human genes 0.000 description 2
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- 229910000085 borane Inorganic materials 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000000125 calcaemic effect Effects 0.000 description 1
- 229960005084 calcitriol Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001845 chromium compounds Chemical class 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 229910000365 copper sulfate Inorganic materials 0.000 description 1
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000010537 deprotonation reaction Methods 0.000 description 1
- PPQUYYAZSOKTQD-UHFFFAOYSA-M diethylalumanylium;iodide Chemical compound CC[Al](I)CC PPQUYYAZSOKTQD-UHFFFAOYSA-M 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- KXONJIYGYMNJHZ-UHFFFAOYSA-N ethyl chloromethanedithioate Chemical compound CCSC(Cl)=S KXONJIYGYMNJHZ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- USSBDBZGEDUBHE-UHFFFAOYSA-L magnesium;2-oxidooxycarbonylbenzoate Chemical compound [Mg+2].[O-]OC(=O)C1=CC=CC=C1C([O-])=O USSBDBZGEDUBHE-UHFFFAOYSA-L 0.000 description 1
- 150000002697 manganese compounds Chemical class 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- CRPQEIZIDRUDJK-UHFFFAOYSA-N methyl chloromethanedithioate Chemical compound CSC(Cl)=S CRPQEIZIDRUDJK-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- GSINXVXKCJCOMC-UHFFFAOYSA-N o-(3,4-dichlorophenyl) chloromethanethioate Chemical compound ClC(=S)OC1=CC=C(Cl)C(Cl)=C1 GSINXVXKCJCOMC-UHFFFAOYSA-N 0.000 description 1
- VOIBZWCASZBGTE-UHFFFAOYSA-N o-(3-chlorophenyl) chloromethanethioate Chemical compound ClC(=S)OC1=CC=CC(Cl)=C1 VOIBZWCASZBGTE-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 150000002908 osmium compounds Chemical class 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- QPCKHSBSZMRDPJ-UHFFFAOYSA-N propan-2-yl chloromethanedithioate Chemical compound CC(C)SC(Cl)=S QPCKHSBSZMRDPJ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 150000004053 quinones Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 150000003304 ruthenium compounds Chemical class 0.000 description 1
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 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
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 238000002525 ultrasonication Methods 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
- C07J7/0005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21
- C07J7/0065—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by an OH group free esterified or etherified
- C07J7/007—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms not substituted in position 21 substituted in position 20 by an OH group free esterified or etherified not substituted in position 17 alfa
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34178696 | 1996-12-20 | ||
| PCT/JP1997/004715 WO1998028266A1 (fr) | 1996-12-20 | 1997-12-19 | Derives de vitamine d 16-ene |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL130484A0 IL130484A0 (en) | 2000-06-01 |
| IL130484A true IL130484A (en) | 2004-07-25 |
Family
ID=18348753
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL13048497A IL130484A (en) | 1996-12-20 | 1997-12-19 | History of -16N-Vitamin-D |
| IL17189097A IL161890A0 (en) | 1996-12-20 | 1997-12-19 | 16-Ene-vitamin d derivatives |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL17189097A IL161890A0 (en) | 1996-12-20 | 1997-12-19 | 16-Ene-vitamin d derivatives |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US6326503B1 (cs) |
| EP (1) | EP0947504B1 (cs) |
| KR (2) | KR100573234B1 (cs) |
| AT (1) | ATE248814T1 (cs) |
| AU (1) | AU720454B2 (cs) |
| CA (1) | CA2275382A1 (cs) |
| DE (1) | DE69724646T2 (cs) |
| DK (1) | DK0947504T3 (cs) |
| ES (1) | ES2206758T3 (cs) |
| IL (2) | IL130484A (cs) |
| NO (1) | NO992981L (cs) |
| PT (1) | PT947504E (cs) |
| WO (1) | WO1998028266A1 (cs) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU7497798A (en) * | 1997-05-16 | 1998-12-08 | F. Hoffmann-La Roche Ag | 3-epi compounds of vitamin d3 and uses thereof |
| HK1042337A1 (en) * | 1999-02-18 | 2002-08-09 | Chugai Seiyaku Kabushiki Kaisha | Method for screening compound having affinity for vitamin d receptor |
| US6960576B2 (en) | 1999-09-13 | 2005-11-01 | Bristol-Myers Squibb Pharma Company | Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production |
| AU2001248777A1 (en) * | 2000-04-19 | 2001-10-30 | Chugai Seiyaku Kabushiki Kaisha | Vitamin d derivatives |
| CN101462994B (zh) * | 2000-06-15 | 2012-11-28 | 中外制药株式会社 | 维生素d衍生物 |
| US7985744B2 (en) * | 2000-06-15 | 2011-07-26 | Chugai Seiyaku Kabushiki Kaisha | Vitamin D derivatives |
| CA2586679A1 (en) | 2004-11-12 | 2006-05-18 | Bioxell Spa | Combined use of vitamin d derivatives and anti-proliferative agents for treating bladder cancer |
| JP4961562B2 (ja) * | 2005-03-04 | 2012-06-27 | 国立大学法人 東京医科歯科大学 | １９−ノルビタミンｄ誘導体 |
| JP5095413B2 (ja) * | 2005-11-30 | 2012-12-12 | 中外製薬株式会社 | 光反応を用いるビタミンｄ誘導体の製法 |
| US8796246B2 (en) | 2006-06-02 | 2014-08-05 | Nippon Shinyaku Co., Ltd. | 9, 10-secopregnane derivative and pharmaceutical |
| US20100196308A1 (en) | 2009-01-27 | 2010-08-05 | Jimenez Joaquin J | Vitamin d3 and analogs thereof for alleviating side effects associated with chemotherapy |
| WO2011019617A2 (en) | 2009-08-14 | 2011-02-17 | Cytotech Labs, Llc | Vitamin d3 and analogs thereof for treating alopecia |
| WO2012151058A1 (en) | 2011-05-03 | 2012-11-08 | Wisconsin Alumni Research Foundation | (20s)-24-(p-toluenesulfonyloxy)-25,26,27-trinorvitamin d3 analogs and their uses |
| HK1222819A1 (zh) | 2013-05-29 | 2017-07-14 | 博格有限责任公司 | 使用维生素d预防或减轻化疗诱发的脱发 |
| CN106279239B (zh) * | 2015-05-29 | 2019-06-28 | 上海彩迩文生化科技有限公司 | 多烯化合物、制备方法及其应用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9007236D0 (en) * | 1990-03-30 | 1990-05-30 | Leo Pharm Prod Ltd | Chemical compounds |
| JPH0680626A (ja) * | 1991-05-09 | 1994-03-22 | Chugai Pharmaceut Co Ltd | 新規な２２−オキサビタミンｄ誘導体 |
| GB9226877D0 (en) * | 1992-12-23 | 1993-02-17 | Leo Pharm Prod Ltd | Chemical compounds |
| JP3415877B2 (ja) * | 1993-03-05 | 2003-06-09 | 中外製薬株式会社 | ２２−オキサビタミンｄ誘導体 |
| US5401733A (en) * | 1993-10-01 | 1995-03-28 | Hoffmann-La Roche Inc. | Stable and active metabolites of 1,25-dihydroxy-16-ene-cholecalciferol |
| US5428029A (en) * | 1993-11-24 | 1995-06-27 | Hoffmann-La Roche Inc. | Vitamin D3 fluorinated analogs |
| US6121469A (en) * | 1993-12-23 | 2000-09-19 | The Regents Of The University Of California | Therapeutically effective 1α,25-dihydroxyvitamin D3 analogs |
| CN1046502C (zh) * | 1994-04-11 | 1999-11-17 | 中外制药株式会社 | 22－硫代维生素d3衍生物 |
| JP3759639B2 (ja) * | 1994-04-11 | 2006-03-29 | 中外製薬株式会社 | ２２−チアビタミン▲ｄ３▼誘導体 |
| PE28297A1 (es) * | 1995-01-26 | 1997-08-20 | Hoffmann La Roche | Empleo dermatologico de derivados de vitamina d |
| JP3715673B2 (ja) * | 1995-03-10 | 2005-11-09 | 中外製薬株式会社 | ビタミンｄ合成中間体の製造方法 |
| US5939408A (en) * | 1996-05-23 | 1999-08-17 | Hoffman-La Roche Inc. | Vitamin D3 analogs |
-
1997
- 1997-12-19 ES ES97949173T patent/ES2206758T3/es not_active Expired - Lifetime
- 1997-12-19 AU AU78727/98A patent/AU720454B2/en not_active Ceased
- 1997-12-19 AT AT97949173T patent/ATE248814T1/de not_active IP Right Cessation
- 1997-12-19 CA CA002275382A patent/CA2275382A1/en not_active Abandoned
- 1997-12-19 KR KR1019997005552A patent/KR100573234B1/ko not_active Expired - Fee Related
- 1997-12-19 WO PCT/JP1997/004715 patent/WO1998028266A1/ja not_active Application Discontinuation
- 1997-12-19 IL IL13048497A patent/IL130484A/en not_active IP Right Cessation
- 1997-12-19 PT PT97949173T patent/PT947504E/pt unknown
- 1997-12-19 DE DE69724646T patent/DE69724646T2/de not_active Expired - Lifetime
- 1997-12-19 EP EP97949173A patent/EP0947504B1/en not_active Expired - Lifetime
- 1997-12-19 IL IL17189097A patent/IL161890A0/xx unknown
- 1997-12-19 KR KR1020057024464A patent/KR20050123185A/ko not_active Ceased
- 1997-12-19 DK DK97949173T patent/DK0947504T3/da active
-
1999
- 1999-06-17 NO NO992981A patent/NO992981L/no not_active Application Discontinuation
-
2000
- 2000-08-18 US US09/640,800 patent/US6326503B1/en not_active Expired - Fee Related
-
2001
- 2001-10-03 US US09/969,350 patent/US6433200B1/en not_active Expired - Fee Related
-
2002
- 2002-06-24 US US10/177,603 patent/US6555699B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2275382A1 (en) | 1998-07-02 |
| EP0947504B1 (en) | 2003-09-03 |
| DE69724646D1 (de) | 2003-10-09 |
| US6433200B1 (en) | 2002-08-13 |
| DE69724646T2 (de) | 2004-06-17 |
| ATE248814T1 (de) | 2003-09-15 |
| NO992981D0 (no) | 1999-06-17 |
| NO992981L (no) | 1999-08-18 |
| AU7872798A (en) | 1998-07-17 |
| KR20000057692A (ko) | 2000-09-25 |
| WO1998028266A1 (fr) | 1998-07-02 |
| KR20050123185A (ko) | 2005-12-29 |
| US20020193616A1 (en) | 2002-12-19 |
| US6555699B2 (en) | 2003-04-29 |
| ES2206758T3 (es) | 2004-05-16 |
| EP0947504A4 (cs) | 1999-11-17 |
| AU720454B2 (en) | 2000-06-01 |
| DK0947504T3 (da) | 2003-11-24 |
| IL130484A0 (en) | 2000-06-01 |
| KR100573234B1 (ko) | 2006-04-24 |
| PT947504E (pt) | 2003-12-31 |
| IL161890A0 (en) | 2005-11-20 |
| US20020032340A1 (en) | 2002-03-14 |
| EP0947504A1 (en) | 1999-10-06 |
| US6326503B1 (en) | 2001-12-04 |
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