UA77033C2 - Спосіб отримання водорозчинних фосфонооксиметильних похідних спирту та фенолу - Google Patents

Спосіб отримання водорозчинних фосфонооксиметильних похідних спирту та фенолу Download PDF

Info

Publication number: UA77033C2
Authority: UA; Ukraine
Prior art keywords: mol; stage; base; reaction; phosphoric acid
Prior art date: 2001-12-21

Application number

UA20040604550A

Other languages

English (en)

Russian (ru)

Ukrainian (uk)

Inventor

Джордж Бонневілле

Грег Делаханті

Ендрю Дж. Уолз

Original Assignee

Mgi Gp Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2001-12-21

Filing date

2002-12-20

Publication date

2006-10-16

2002-12-20 Application filed by Mgi Gp Inc filed Critical Mgi Gp Inc

2006-10-16 Publication of UA77033C2 publication Critical patent/UA77033C2/uk

Links

238000000034 method Methods 0.000 title claims abstract description 39
239000003814 drug Substances 0.000 title claims abstract description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 16
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 title claims abstract description 15
VBKBIDUVUIYPEC-UHFFFAOYSA-N phosphonooxymethoxymethyl dihydrogen phosphate Chemical class OP(O)(=O)OCOCOP(O)(O)=O VBKBIDUVUIYPEC-UHFFFAOYSA-N 0.000 title abstract 2
-1 phosphonooxymethyl Chemical class 0.000 claims abstract description 16
OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 claims abstract description 15
229940079593 drug Drugs 0.000 claims abstract description 14
VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims abstract description 12
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims abstract description 11
229940127093 camptothecin Drugs 0.000 claims abstract description 11
VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims abstract description 11
239000001257 hydrogen Substances 0.000 claims abstract description 11
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
229960004134 propofol Drugs 0.000 claims abstract description 11
GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims abstract description 10
150000001768 cations Chemical class 0.000 claims abstract description 10
229910001413 alkali metal ion Inorganic materials 0.000 claims abstract description 9
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims abstract description 6
229930105110 Cyclosporin A Natural products 0.000 claims abstract description 6
108010036949 Cyclosporine Proteins 0.000 claims abstract description 6
229930003427 Vitamin E Natural products 0.000 claims abstract description 5
229960005420 etoposide Drugs 0.000 claims abstract description 5
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims abstract description 5
WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims abstract description 5
229940046009 vitamin E Drugs 0.000 claims abstract description 5
239000011709 vitamin E Substances 0.000 claims abstract description 5
235000019165 vitamin E Nutrition 0.000 claims abstract description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 5
JPOXNPPZZKNXOV-UHFFFAOYSA-N bromochloromethane Chemical compound ClCBr JPOXNPPZZKNXOV-UHFFFAOYSA-N 0.000 claims description 30
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 28
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
239000002904 solvent Substances 0.000 claims description 21
239000002585 base Substances 0.000 claims description 18
238000006243 chemical reaction Methods 0.000 claims description 17
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
MKTOTUYWFIPBRT-UHFFFAOYSA-N [Na].[Na].P(=O)(O)(O)OC1=C(C(=C(C(=C1)C(C)C)O)C(C)C)C Chemical compound [Na].[Na].P(=O)(O)(O)OC1=C(C(=C(C(=C1)C(C)C)O)C(C)C)C MKTOTUYWFIPBRT-UHFFFAOYSA-N 0.000 claims description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
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 claims description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
150000001413 amino acids Chemical class 0.000 claims description 3
229910052744 lithium Inorganic materials 0.000 claims description 3
239000003880 polar aprotic solvent Substances 0.000 claims description 3
229910052700 potassium Inorganic materials 0.000 claims description 3
239000011591 potassium Substances 0.000 claims description 3
229910052708 sodium Inorganic materials 0.000 claims description 3
239000011734 sodium Substances 0.000 claims description 3
LHVRNLFXKYWAQL-UHFFFAOYSA-N 1-(chloromethoxy)-2,3-di(propan-2-yl)benzene Chemical compound CC(C)C1=CC=CC(OCCl)=C1C(C)C LHVRNLFXKYWAQL-UHFFFAOYSA-N 0.000 claims description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 2
229910000102 alkali metal hydride Inorganic materials 0.000 claims description 2
150000008046 alkali metal hydrides Chemical class 0.000 claims description 2
150000003973 alkyl amines Chemical class 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 claims description 2
150000002500 ions Chemical class 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
150000003222 pyridines Chemical class 0.000 claims description 2
229910000104 sodium hydride Inorganic materials 0.000 claims description 2
239000012312 sodium hydride Substances 0.000 claims description 2
239000000010 aprotic solvent Substances 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
229960001265 ciclosporin Drugs 0.000 abstract description 2
238000004519 manufacturing process Methods 0.000 abstract description 2
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000000243 solution Substances 0.000 description 15
239000000203 mixture Substances 0.000 description 14
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
239000003921 oil Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
239000007787 solid Substances 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 5
239000012044 organic layer Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
XYMTUFXXCMZHCU-UHFFFAOYSA-N 2-(chloromethoxy)-1,3-di(propan-2-yl)benzene Chemical compound CC(C)C1=CC=CC(C(C)C)=C1OCCl XYMTUFXXCMZHCU-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
230000008034 disappearance Effects 0.000 description 4
150000002431 hydrogen Chemical class 0.000 description 4
239000007858 starting material Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
WVYWICLMDOOCFB-UHFFFAOYSA-N 4-methyl-2-pentanol Chemical compound CC(C)CC(C)O WVYWICLMDOOCFB-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
239000002253 acid Substances 0.000 description 3
230000000711 cancerogenic effect Effects 0.000 description 3
231100000315 carcinogenic Toxicity 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000000284 extract Substances 0.000 description 3
210000003739 neck Anatomy 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 2
235000010469 Glycine max Nutrition 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
206010061535 Ovarian neoplasm Diseases 0.000 description 2
PMTZVNXRAHOUTA-UHFFFAOYSA-N [4-hydroxy-2-methyl-3,5-di(propan-2-yl)phenyl] dihydrogen phosphate Chemical compound P(=O)(O)(O)OC1=C(C(=C(C(=C1)C(C)C)O)C(C)C)C PMTZVNXRAHOUTA-UHFFFAOYSA-N 0.000 description 2
238000009835 boiling Methods 0.000 description 2
239000012267 brine Substances 0.000 description 2
210000001072 colon Anatomy 0.000 description 2
208000029742 colonic neoplasm Diseases 0.000 description 2
150000001875 compounds Chemical class 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
238000004817 gas chromatography Methods 0.000 description 2
239000008187 granular material Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
238000002390 rotary evaporation Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
GCKMFJBGXUYNAG-UHFFFAOYSA-N 17alpha-methyltestosterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C)(O)C1(C)CC2 GCKMFJBGXUYNAG-UHFFFAOYSA-N 0.000 description 1
241001519451 Abramis brama Species 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
241000759909 Camptotheca Species 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
244000025361 Ficus carica Species 0.000 description 1
235000008730 Ficus carica Nutrition 0.000 description 1
244000068988 Glycine max Species 0.000 description 1
NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
206010061902 Pancreatic neoplasm Diseases 0.000 description 1
235000016496 Panda oleosa Nutrition 0.000 description 1
240000000220 Panda oleosa Species 0.000 description 1
208000010378 Pulmonary Embolism Diseases 0.000 description 1
108010067445 RA V Proteins 0.000 description 1
208000015634 Rectal Neoplasms Diseases 0.000 description 1
208000005718 Stomach Neoplasms Diseases 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000013543 active substance Substances 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229940087168 alpha tocopherol Drugs 0.000 description 1
230000003444 anaesthetic effect Effects 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
KUCQYCKVKVOKAY-CTYIDZIISA-N atovaquone Chemical compound C1([C@H]2CC[C@@H](CC2)C2=C(C(C3=CC=CC=C3C2=O)=O)O)=CC=C(Cl)C=C1 KUCQYCKVKVOKAY-CTYIDZIISA-N 0.000 description 1
229960003159 atovaquone Drugs 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
244000309464 bull Species 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
229940121657 clinical drug Drugs 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
208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 1
229960000766 danazol Drugs 0.000 description 1
229960000691 diiodohydroxyquinoline Drugs 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
UXZFQZANDVDGMM-UHFFFAOYSA-N iodoquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(I)C2=C1 UXZFQZANDVDGMM-UHFFFAOYSA-N 0.000 description 1
230000002262 irrigation Effects 0.000 description 1
238000003973 irrigation Methods 0.000 description 1
244000145841 kine Species 0.000 description 1
239000010410 layer Substances 0.000 description 1
229960004194 lidocaine Drugs 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
208000020816 lung neoplasm Diseases 0.000 description 1
229940126601 medicinal product Drugs 0.000 description 1
201000001441 melanoma Diseases 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229960001566 methyltestosterone Drugs 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
229930014626 natural product Natural products 0.000 description 1
230000002611 ovarian Effects 0.000 description 1
238000010979 pH adjustment Methods 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
229940002612 prodrug Drugs 0.000 description 1
239000000651 prodrug Substances 0.000 description 1
239000008213 purified water Substances 0.000 description 1
206010038038 rectal cancer Diseases 0.000 description 1
201000001275 rectum cancer Diseases 0.000 description 1
239000004576 sand Substances 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
238000009958 sewing Methods 0.000 description 1
230000008667 sleep stage Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
229960000984 tocofersolan Drugs 0.000 description 1
TUBWTFZPLDUNIL-HJJYVODLSA-N tpc-a Chemical compound O.O.O.O.O.C1=CC(OC)=CC=C1C[C@H](N(C)C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](N(C1=O)C)C2)C(=O)N[C@H](C)C(=O)N(C)[C@@H]1CC(C=C1)=CC=C1OC1=CC2=CC=C1O.C1=CC(OC)=CC=C1C[C@H](N(C)C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](N(C1=O)C)C2)C(=O)N[C@H](C)C(=O)N(C)[C@@H]1CC(C=C1)=CC=C1OC1=CC2=CC=C1O.C1=CC(OC)=CC=C1C[C@H](N(C)C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](N(C1=O)C)C2)C(=O)N[C@H](C)C(=O)N(C)[C@@H]1CC(C=C1)=CC=C1OC1=CC2=CC=C1O.C1=CC(OC)=CC=C1C[C@H](N(C)C(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](N(C1=O)C)C2)C(=O)N[C@H](C)C(=O)N(C)[C@@H]1CC(C=C1)=CC=C1OC1=CC2=CC=C1O TUBWTFZPLDUNIL-HJJYVODLSA-N 0.000 description 1
QQXLDOJGLXJCSE-KNVOCYPGSA-N tropinone Chemical compound C1C(=O)C[C@H]2CC[C@@H]1N2C QQXLDOJGLXJCSE-KNVOCYPGSA-N 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
239000002076 α-tocopherol Substances 0.000 description 1
235000004835 α-tocopherol Nutrition 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
- C07K7/645—Cyclosporins; Related peptides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P23/00—Anaesthetics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- 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
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/091—Esters of phosphoric acids with hydroxyalkyl compounds with further substituents on alkyl
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/6552—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring
- C07F9/65522—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a six-membered ring condensed with carbocyclic rings or carbocyclic ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Biochemistry (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Biophysics (AREA)
Anesthesiology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Genetics & Genomics (AREA)
Transplantation (AREA)
Neurosurgery (AREA)
Obesity (AREA)
Biomedical Technology (AREA)
Diabetes (AREA)
Neurology (AREA)
Nutrition Science (AREA)
Hematology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Saccharide Compounds (AREA)
Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

UA20040604550A 2001-12-21 2002-12-20 Спосіб отримання водорозчинних фосфонооксиметильних похідних спирту та фенолу UA77033C2 (uk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US34186701P	2001-12-21	2001-12-21
PCT/US2002/040748 WO2003059255A2 (fr)	2001-12-21	2002-12-20	Procede de preparation de derives de phosphonooxymethyle d'alcool et de phenol

Publications (1)

Publication Number	Publication Date
UA77033C2 true UA77033C2 (uk)	2006-10-16

Family

ID=23339347

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA20040604550A UA77033C2 (uk)	2001-12-21	2002-12-20	Спосіб отримання водорозчинних фосфонооксиметильних похідних спирту та фенолу

Country Status (20)

Country	Link
US (2)	US7229978B2 (fr)
EP (2)	EP1471920B1 (fr)
JP (2)	JP4369237B2 (fr)
KR (3)	KR100937162B1 (fr)
CN (2)	CN100413508C (fr)
AT (1)	ATE423563T1 (fr)
AU (2)	AU2002360682B2 (fr)
CA (1)	CA2470423C (fr)
DE (1)	DE60231336D1 (fr)
ES (1)	ES2322245T3 (fr)
HU (1)	HU230216B1 (fr)
IL (1)	IL162550A (fr)
IN (1)	IN2012DN01975A (fr)
MX (1)	MXPA04005892A (fr)
NZ (1)	NZ533535A (fr)
PL (1)	PL205940B1 (fr)
RU (1)	RU2310659C2 (fr)
UA (1)	UA77033C2 (fr)
WO (1)	WO2003059255A2 (fr)
ZA (1)	ZA200404579B (fr)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU2003231765B9 (en)	2002-04-26	2010-01-28	Gilead Sciences, Inc.	Cellular accumulation of phosphonate analogs of HIV protease inhibitor compounds and the compounds as such
WO2005002626A2 (fr)	2003-04-25	2005-01-13	Gilead Sciences, Inc.	Composes de phosphonate therapeutiques
US7470724B2 (en)	2003-04-25	2008-12-30	Gilead Sciences, Inc.	Phosphonate compounds having immuno-modulatory activity
US7300924B2 (en)	2003-04-25	2007-11-27	Gilead Sciences, Inc.	Anti-infective phosphonate analogs
EA200501678A1 (ru) *	2003-04-25	2006-10-27	Джилид Сайэнс, Инк.	Фосфонатсодержащие иммуномодулирующие соединения (варианты), способ их получения, фармацевтическая композиция, лекарственная форма на их основе и способы модулирования или ингибирования иммунного ответа у млекопитающего
US7452901B2 (en)	2003-04-25	2008-11-18	Gilead Sciences, Inc.	Anti-cancer phosphonate analogs
JP2006524710A (ja)	2003-04-25	2006-11-02	ギリアードサイエンシーズ，インコーポレイテッド	キナーゼインヒビターホスホネート抱合体
US7407965B2 (en)	2003-04-25	2008-08-05	Gilead Sciences, Inc.	Phosphonate analogs for treating metabolic diseases
WO2004096287A2 (fr)	2003-04-25	2004-11-11	Gilead Sciences, Inc.	Composes de phosphonate inhibiteurs de l'inosine monophosphate deshydrogenase
US7432261B2 (en)	2003-04-25	2008-10-07	Gilead Sciences, Inc.	Anti-inflammatory phosphonate compounds
PL1628685T3 (pl)	2003-04-25	2011-05-31	Gilead Sciences Inc	Przeciwwirusowe analogi fosfonianowe
US20040225022A1 (en) *	2003-05-09	2004-11-11	Desai Neil P.	Propofol formulation containing reduced oil and surfactants
AU2004286239A1 (en)	2003-10-24	2005-05-12	Gilead Sciences, Inc.	Methods and compositions for identifying therapeutic compounds
WO2005044308A1 (fr)	2003-10-24	2005-05-19	Gilead Sciences, Inc.	Analogues phosphonates d'antimetabolites
US7427624B2 (en)	2003-10-24	2008-09-23	Gilead Sciences, Inc.	Purine nucleoside phosphorylase inhibitory phosphonate compounds
DE602004019815D1 (de)	2003-12-22	2009-04-16	Gilead Sciences Inc	4'-substituierte carbovir- und abacavir-derivate sowie verwandte verbindungen mit hiv- und hcv-antiviraler wirkung
EP1778251B1 (fr)	2004-07-27	2011-04-13	Gilead Sciences, Inc.	Conjugues de phosphonate nucleosidique comme agents anti-vih
AU2009268681B2 (en)	2008-07-08	2014-10-02	Gilead Sciences, Inc.	Salts of HIV inhibitor compounds
KR20100032803A (ko) *	2008-09-18	2010-03-26	씨제이제일제당 (주)	아데포비어디피복실의 개선된 제조방법
CN101845057B (zh) *	2009-03-27	2013-10-23	四川大学	取代苯酚的甲缩醛磷酸盐麻醉镇静药用化合物及制备方法
US9150600B2 (en)	2009-05-07	2015-10-06	Regents Of The University Of Minnesota	Triptolide prodrugs
EP2427467B1 (fr) *	2009-05-07	2015-08-05	Regents of the University of Minnesota	Promédicaments à base de triptolide
JP2012140330A (ja) *	2010-12-28	2012-07-26	Tosoh Corp	水溶性リン酸エステルの精製方法
ITMI20110580A1 (it) *	2011-04-08	2012-10-09	Chemelectiva S R L	Iintermedi utili per la preparazione di fospropofol e processo per la loro preparazione
UY34072A (es)	2011-05-17	2013-01-03	Novartis Ag	Derivados sustituidos de indol
CN102351895A (zh) *	2011-08-08	2012-02-15	陕西合成药业有限公司	甲磷丙泊酚二钠水合物及其制备方法和用途
CN102382133B (zh) *	2011-12-02	2016-03-23	陕西合成药业股份有限公司	一种磷丙泊酚钠的制备及纯化方法
CN102516099B (zh) *	2011-12-02	2013-07-17	成都苑东药业有限公司	一种水溶性三醇胺的衍生物
CN102399236A (zh) *	2011-12-27	2012-04-04	上海立科药物化学有限公司	磷丙泊酚钠的合成方法
CN102603798A (zh) *	2012-02-14	2012-07-25	陕西合成药业有限公司	一种唑系化合物水溶性前药的制备方法
ES2746987T3 (es) *	2013-05-09	2020-03-09	Sichuan Haisco Pharmaceutical Co Ltd	Derivado de fenol y método de preparación y uso en medicina de los mismos
US11331271B2 (en)	2016-05-27	2022-05-17	The Johns Hopkins University	Buccal, sublingual and intranasal delivery of fospropofol
EP3661937B1 (fr)	2017-08-01	2021-07-28	Gilead Sciences, Inc.	Formes crystallines d'éthyl ((s)-((((2r,5r)-5-(6-amino-9h-purin-9-yl)-4-fluoro-2,5-dihydrofuran-2-yl)oxy)méthyl)(phénoxy)phosphoryl)-l-alaninate (gs-9131) pour le traitement des infections virales
CN109456360B (zh) *	2018-12-17	2021-05-14	河南中医药大学	一种磷丙泊酚钠的制备方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2833827A (en)	1955-01-17	1958-05-06	Bayer Ag	Tri (3, 5-di lower alkyl-4-hydroxy phenyl)-sulfonium chlorides and method of preparing same
GB814278A (en)	1956-11-13	1959-06-03	Bataafsche Petroleum	Process for the preparation of 2.4.6 trialkylated phenols
JPS56131594A (en) *	1980-03-17	1981-10-15	Mitsui Toatsu Chem Inc	Preparation of alkyl phosphate
JPH04282337A (ja) *	1991-03-08	1992-10-07	Fuji Photo Film Co Ltd	２−アリールオキシ−１−クロルプロパンの製造方法
TW354293B (en) *	1995-06-06	1999-03-11	Bristol Myers Squibb Co	Prodrugs of paclitaxel derivatives
US6201257B1 (en) *	1996-10-10	2001-03-13	Advanced Scientific Concepts, Inc.	Semiconductor X-ray photocathodes devices
US6204257B1 (en) *	1998-08-07	2001-03-20	Universtiy Of Kansas	Water soluble prodrugs of hindered alcohols

2002
- 2002-12-20 CA CA2470423A patent/CA2470423C/fr not_active Expired - Fee Related
- 2002-12-20 AU AU2002360682A patent/AU2002360682B2/en not_active Ceased
- 2002-12-20 AT AT02795960T patent/ATE423563T1/de not_active IP Right Cessation
- 2002-12-20 KR KR1020087007455A patent/KR100937162B1/ko not_active Expired - Fee Related
- 2002-12-20 IN IN1975DEN2012 patent/IN2012DN01975A/en unknown
- 2002-12-20 KR KR1020107017896A patent/KR20100101011A/ko not_active Withdrawn
- 2002-12-20 PL PL370489A patent/PL205940B1/pl unknown
- 2002-12-20 UA UA20040604550A patent/UA77033C2/uk unknown
- 2002-12-20 CN CNB028258827A patent/CN100413508C/zh not_active Expired - Fee Related
- 2002-12-20 US US10/498,013 patent/US7229978B2/en not_active Expired - Fee Related
- 2002-12-20 DE DE60231336T patent/DE60231336D1/de not_active Expired - Lifetime
- 2002-12-20 JP JP2003559420A patent/JP4369237B2/ja not_active Expired - Fee Related
- 2002-12-20 HU HU0500139A patent/HU230216B1/hu not_active IP Right Cessation
- 2002-12-20 CN CN200810145160XA patent/CN101367834B/zh not_active Expired - Fee Related
- 2002-12-20 EP EP02795960A patent/EP1471920B1/fr not_active Expired - Lifetime
- 2002-12-20 NZ NZ533535A patent/NZ533535A/en not_active IP Right Cessation
- 2002-12-20 KR KR1020047009287A patent/KR101016969B1/ko not_active Expired - Fee Related
- 2002-12-20 RU RU2004120071/04A patent/RU2310659C2/ru not_active IP Right Cessation
- 2002-12-20 EP EP09153421A patent/EP2058320B1/fr not_active Expired - Lifetime
- 2002-12-20 ES ES02795960T patent/ES2322245T3/es not_active Expired - Lifetime
- 2002-12-20 WO PCT/US2002/040748 patent/WO2003059255A2/fr not_active Ceased
2004
- 2004-06-09 ZA ZA200404579A patent/ZA200404579B/xx unknown
- 2004-06-16 IL IL162550A patent/IL162550A/en not_active IP Right Cessation
- 2004-06-16 MX MXPA04005892A patent/MXPA04005892A/es active IP Right Grant
2006
- 2006-10-26 US US11/586,576 patent/US7534776B2/en not_active Expired - Fee Related
2008
- 2008-09-08 AU AU2008212060A patent/AU2008212060B2/en not_active Ceased
2009
- 2009-03-03 JP JP2009049261A patent/JP4617382B2/ja not_active Expired - Fee Related

Also Published As

Publication number	Publication date
IL162550A (en)	2013-08-29
CA2470423C (fr)	2011-03-15
ATE423563T1 (de)	2009-03-15
JP4617382B2 (ja)	2011-01-26
CN101367834A (zh)	2009-02-18
US20050124787A1 (en)	2005-06-09
RU2004120071A (ru)	2006-01-10
ES2322245T3 (es)	2009-06-18
EP1471920A4 (fr)	2006-02-15
KR101016969B1 (ko)	2011-02-25
CN100413508C (zh)	2008-08-27
KR100937162B1 (ko)	2010-01-15
JP2009149682A (ja)	2009-07-09
WO2003059255A3 (fr)	2004-02-19
DE60231336D1 (de)	2009-04-09
KR20100101011A (ko)	2010-09-15
CN101367834B (zh)	2012-04-18
PL370489A1 (en)	2005-05-30
KR20080033551A (ko)	2008-04-16
EP2058320A1 (fr)	2009-05-13
EP1471920B1 (fr)	2009-02-25
CN1671395A (zh)	2005-09-21
JP2005514431A (ja)	2005-05-19
US7229978B2 (en)	2007-06-12
IN2012DN01975A (fr)	2015-08-21
RU2310659C2 (ru)	2007-11-20
MXPA04005892A (es)	2004-11-01
AU2008212060B2 (en)	2011-10-27
ZA200404579B (en)	2006-03-29
AU2002360682A1 (en)	2003-07-30
US7534776B2 (en)	2009-05-19
EP2058320B1 (fr)	2012-11-21
WO2003059255A2 (fr)	2003-07-24
NZ533535A (en)	2005-12-23
HUP0500139A2 (hu)	2005-05-30
KR20040072659A (ko)	2004-08-18
PL205940B1 (pl)	2010-06-30
CA2470423A1 (fr)	2003-07-24
US20070043206A1 (en)	2007-02-22
AU2008212060A1 (en)	2008-10-02
HUP0500139A3 (en)	2005-11-28
EP1471920A2 (fr)	2004-11-03
AU2002360682B2 (en)	2008-06-26
JP4369237B2 (ja)	2009-11-18
HU230216B1 (hu)	2015-10-28

Publication	Publication Date	Title
KR101016969B1 (ko)	2011-02-25	알콜 및 페놀의 수용성 포스포노옥시메틸 유도체를제조하는 방법
EA029775B1 (ru)	2018-05-31	Применение 1,3,5-триазин-2-ил фосфорамидатного соединения в синтезе софосбувира
KR102042411B1 (ko)	2019-11-08	데커신 유도체를 포함하는 결핵 예방 또는 치료용 조성물
MX2013009501A (es)	2014-02-03	Metodos para sintetizar derivados del precursor z de molibdopterina.
EP1916251A1 (fr)	2008-04-30	Sels d érianine, leurs procédés de préparation et compositions pharmaceutiques contenant ceux-ci
ZA200404423B (en)	2006-05-31	Genes encoding for carbon metabolism ad energy producing proteins
JPH10507462A (ja)	1998-07-21	エピポドフィロトキシンの水溶性誘導体、その製法、薬剤としてのその用途および抗癌治療におけるその意図的使用
DE112014001871B4 (de)	2019-11-14	Verfahren zur Herstellung von 3,4,5-Tricaffeoylchinasäure
JP2022109980A (ja)	2022-07-28	ベンゾアゼピン化合物の製造方法
HK1128292A (en)	2009-10-23	Process for preparing water-soluble phosphonooxymethyl derivatives of alcohol and phenol
HK1069336B (en)	2009-11-13	Process for preparing water-soluble phosphonooxymethyl derivatives of alcohol and phenol
HK1069336A1 (en)	2005-05-20	Process for preparing water-soluble phosphonooxymethyl derivatives of alcohol and phenol
AU2007335991B2 (en)	2013-03-28	Polyalkyloxydibenz ( c, e) oxepine derivatives as medicaments
CN110407868A (zh)	2019-11-05	一种二苯乙烯或二苯乙烷类化合物的磷酰化物制备方法
PL228421B1 (pl)	2018-03-30	1’-[(3,7-Dimetylo-3-winylookta-6-enylo]-2’-hydroksy-sn-glicero- 3’-fosfocholina i sposób jej otrzymywania