CS270596B2 - Method of 4-demethoxyanthracycline derivatives production - Google Patents
Method of 4-demethoxyanthracycline derivatives production Download PDFInfo
- Publication number
- CS270596B2 CS270596B2 CS887117A CS711788A CS270596B2 CS 270596 B2 CS270596 B2 CS 270596B2 CS 887117 A CS887117 A CS 887117A CS 711788 A CS711788 A CS 711788A CS 270596 B2 CS270596 B2 CS 270596B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- formula
- demethoxy
- solution
- aqueous
- amino
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 9
- 238000004519 manufacturing process Methods 0.000 title claims 2
- ZUFQFGSMHXKORU-UHFFFAOYSA-N 9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C(O)=C1C(O)CC(C(=O)C)(O)CC1=C2O ZUFQFGSMHXKORU-UHFFFAOYSA-N 0.000 claims abstract description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 4
- 235000010288 sodium nitrite Nutrition 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims 5
- 239000007864 aqueous solution Substances 0.000 claims 3
- 238000000605 extraction Methods 0.000 claims 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims 1
- 238000001704 evaporation Methods 0.000 claims 1
- 230000008020 evaporation Effects 0.000 claims 1
- 239000012044 organic layer Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 229930182470 glycoside Natural products 0.000 abstract description 4
- 150000002338 glycosides Chemical class 0.000 abstract description 4
- 229940045799 anthracyclines and related substance Drugs 0.000 abstract description 3
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 abstract description 2
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 abstract description 2
- 229960000908 idarubicin Drugs 0.000 abstract description 2
- YOFDHOWPGULAQF-MQJDWESPSA-N (7s,9s)-9-acetyl-6,7,9,11-tetrahydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical class C1[C@@](O)(C(C)=O)C[C@H](O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-MQJDWESPSA-N 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 230000000259 anti-tumor effect Effects 0.000 abstract 1
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 3
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 238000006193 diazotization reaction Methods 0.000 description 3
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000031709 bromination Effects 0.000 description 1
- 238000005893 bromination reaction Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Saccharide Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
57) Řešení spočívá v novén způsobu výroby 4-demethoxydaunomycinonu, známého aglykonu 4-demethoxyanthracyklinových gíykosidů. Tento nový postup se provádí diazotací aminoskupiny v poloze 4 ve 4-demethoxy-4aminodaunomycinonu s následnou imírnou redukcí takto vzniklé diazohiové sloučeniny působením 50% vodného roztoku kyseliny fosforné při teplotě místnosti.
270 596 (11) (13) В 2 (51) Int. Clí
Způsob podle vynálezu se týká nové metody pro výrobu známé látky 4-demethoxydaunomycinonu, která je cenným meziproduktem pro 4-demethoxy-anthracyklinové glykosidy po kondenzaci s vhodnými deriváty cukrů.
V československém patentovém spisu 270585 qe popisuje způsob výroby nového aglykonu 4-demethoxy-4-amino-7-deoxydaunomycinonu vzorce·IX· · * 1
katalytickou deben2ylací 4-demethoxy-4-benzylamino-7-deoxydaunomycinonu vzorce VIII
Z takto získaného meziproduktu vzorce IX je možno snadno získat 4-demethoxy-4-amino -7-deoxydaunomycinon obecného vzorce XVa nebo 4-demethoxy-4-daunomycinon obecného vzorce XVb .
(XVa, b) (a: R4 = H b: R4 » OH)
Anthracykli попу obecného vzorce XVa,b, které nesou aminoskupinu v poloze 4, je pak možno převést na odpovídající deaminoderiváty obecného vzorce XIV a, b
| 1 | (XIVB.b) | ( 8 · йд a H, b: = OH) |
diazotací s následnou mírnou redukcí takto získaných diazoniových sloučenin. Výchozími látkami jsou tedy 4-demethoxy-4-amino-7-deoxydaunomycinon vzorce XVa, v němž znamená atom vodíku a 4-demethoxy-4-aminodaunomycinon obecného vzorce XVb, v němž R^ znamená hy droxyskupinu. Odstranění aminoskupiny v poloze 4 diazotací s mírnou redukcí vede к získá ní známého 4-demethoxy-7-deoxydaunomycinonu vzorce XlVa, v němž. R^ znamená atom vodíku nebo 4-demetoxydaunomycinonu vzorce XlVb, v němž R^ znamená hydroxylovou skupinu. Jak je dále znázorněno, provádí se diazotace s výhodou při použití vodného roztoku dusitanu sod ného a mírná redukce se s výhodou provádí působením kyseliny fosíorné.
1) vodný roztok NaNO2 ----------------> 2) kyselina ťosťorná
kde znamená atom vodíku nebo hydroxylovou skupinu.
Sloučeninu obecného vzorce XVa, v němž R^ znamená atom vodíku, je možno snadno převést na sloučeninu obecného vzorce XVb, v němž R^ znamená hydroxylovou skupinu standardními postupy. S výhodou se postupuje tak, že se uvede do reakce 4-demethoxy-4-amino-7-d®xydaunomycinon vzorce XVa nebo 4-demethoxy-4-aminodaunomycinon vzorce XVb, rozpuštěný ve
37% vodném roztoku kyseliny chlorovodíkové při teplotě v rozmezí 0 až 5 °C po dobu 1 hodiny s vodným roztokem dusitanu sodného a pak ještě na 5 hodin při teplotě místnosti za energického míchání s vodným roztokem kyseliny fosforné o koncentraci 50 %, pak se reakč ní směs extrahuje methylendichloridem a rozpouštědlo se odstraní za sníženého tlaku.
I t
4-Demethoxy-7-deoxydaunomycinon vzorce. XlVa je*, možno převést na 4-demethoxydaunomycinon vzorce XlVb zavedením hydroxylové skupiny do polohy 1. Toho je možno dosáhnout zná mým způsobem bromací v poloze 7, například, působením bromu nebo N-bromsukcinimidu (NBS) s následným působením hydroxidu alkalického kovu nebo octanu stříbrného nebo methanolýzou takto získaného acetátu. v.
4-Demethoxydaunomycinon vzorce XlVb je aglykonem známé a Široce používané látky 4-demethoxydaunorubicinu. · t
Praktické provedení způsobu podle vynálezu bude osvětleno následujícími příklady.
Příklad 1
Způsob výroby 4-demethoxy-7-deoxydaunomycinonu (XlVa)
Claims (1)
- l,78g, 5 mmolů 4-demethoxy-4-amino-7-deoxydaunomycinonu vzorce IX se rozpustí v 75 ml vodného 37% roztoku kyseliny chlorovodíkové, roztok se zchladí na 0 až 5 °C a pak se při dá 75 ml vodného roztoku s obsahem 0,6 g dusitanu sodného. Směs se 1 hodinu míchá při tqplotě 0 až 5 °C. Pak se přidá 25 ml vodného roztoku v 50% kyseliny fosforné a směs se pd< udržuje 5 hodin na teplotě místnosti za energického míchání.Pak se roztok zředí přidáním 200 ml vody a extrahuje se methylendichloridem. Organická vrstva se oddělí, vysuší se bezvodým síranem sodným a pak ae rozpouštědlo odstraní za sníženého tlaku, čímž se v kvantitativním výtěžku získá 1,7 g 4-demathoxy-7-deoxydaunomy - .cinonu vzorce XlVa, který je analyticky srovnatelný se standardním vzorkem.Příklad 2Způsob výroby 4-demethoxydaunomycinonu (XlVb)1,86 g, 5 mmolů, 4-demethoxy-4-aminodaunomycinonu vzorce II se převede na odpovídající 4-demethoxydaunomycinon vzorce XlVb svrchu uvedeným způsobem. Ve výtěžku 1,8 g se získá sloučenina XlVb, analyticky srovnatelná se standardním vzorkem.PŘEDMÉT VYNÍLE.ZUZpůsob výroby 4-demethoxy-7-deoxydaunomycinonu nebo 4-demethoxydaunomycinonu obecného vzorce XlVa, bCS 270596 82 (XlVa, b) (a: B^ = H, b: B, = OH) kde znamená atom vodíku nebo hydroxylovou skupinu, vyznačující se tím, že se 4-demethoxy-4-amino-7-deoxydaunomycinon vzorce XVa nebo 4-deme thoxy-4-aminodaunomycinon vzorce XVb .(XVa, b) (a: S.H, b: = OH) kde má svrchu uvedený význam, rozpustí v 37% vodném roztoku kyseliny chlorovodíkové a na tento roztok se působí 1 hodinu při teplotě 0 až 5 °C za míchání vodným roztokem dusitanu sodného, načež se roztok uvede do reakce na 5 hodin s 50% vodným roztokem kyseliny fosforné při teplotě místnosti , čímž se po extrakci methylendichlorldem a odpařením extrakčního rozpouštědla za snížonóřo tlaku získá v kvantitativním výtěžku sloučenina obecného vzorce XlVa, b.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878709353A GB8709353D0 (en) | 1987-04-21 | 1987-04-21 | 4-demethoxy-4-amino-anthracyclines |
| GB888803302A GB8803302D0 (en) | 1988-02-12 | 1988-02-12 | Conversion of 4-demethoxy-4-amino anthracyclinones into 4-demethoxy-anthracyclinones |
| CS882658A CS270585B2 (en) | 1987-04-21 | 1988-04-19 | Method of 4-demethoxy-4-aminoanthracycline derivatives production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS711788A2 CS711788A2 (en) | 1989-11-14 |
| CS270596B2 true CS270596B2 (en) | 1990-07-12 |
Family
ID=26292154
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS882658A CS270585B2 (en) | 1987-04-21 | 1988-04-19 | Method of 4-demethoxy-4-aminoanthracycline derivatives production |
| CS887117A CS270596B2 (en) | 1987-04-21 | 1988-10-27 | Method of 4-demethoxyanthracycline derivatives production |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS882658A CS270585B2 (en) | 1987-04-21 | 1988-04-19 | Method of 4-demethoxy-4-aminoanthracycline derivatives production |
Country Status (26)
| Country | Link |
|---|---|
| US (2) | US4965351A (cs) |
| EP (2) | EP0426653B1 (cs) |
| JP (1) | JP2651414B2 (cs) |
| KR (1) | KR880012627A (cs) |
| CN (2) | CN1022038C (cs) |
| AT (2) | ATE83239T1 (cs) |
| AU (2) | AU600816B2 (cs) |
| CA (2) | CA1315775C (cs) |
| CS (2) | CS270585B2 (cs) |
| DE (2) | DE3876482T2 (cs) |
| DK (2) | DK170405B1 (cs) |
| ES (2) | ES2093034T3 (cs) |
| FI (1) | FI89263C (cs) |
| GR (2) | GR3007163T3 (cs) |
| HR (2) | HRP920920B1 (cs) |
| HU (2) | HU200188B (cs) |
| IE (1) | IE63510B1 (cs) |
| IL (1) | IL86088A (cs) |
| MY (2) | MY103365A (cs) |
| NO (1) | NO168702C (cs) |
| NZ (1) | NZ224252A (cs) |
| PT (2) | PT87270B (cs) |
| SI (1) | SI8810759A8 (cs) |
| SU (2) | SU1614764A3 (cs) |
| YU (2) | YU46455B (cs) |
| ZA (1) | ZA882732B (cs) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8803301D0 (en) * | 1988-02-12 | 1988-03-09 | Erba Carlo Spa | Process for preparation of 4-demethoxy-daunomycinone aglycone of 4-demethoxy-daunorubicin |
| GB8818167D0 (en) * | 1988-07-29 | 1988-09-01 | Erba Carlo Spa | Novel 4-substituted anthracyclinones & process for their preparation |
| US5412081A (en) * | 1989-02-07 | 1995-05-02 | Farmitalia Carlo Erba S.R.L. | New 4'-epi-4'-amino anthracyclines |
| GB8904794D0 (en) * | 1989-03-02 | 1989-04-12 | Erba Carlo Spa | Process for preparing anthracyclinones |
| GB8905668D0 (en) * | 1989-03-13 | 1989-04-26 | Erba Carlo Spa | New 3'-(4-morpholinyl)-and 3'-(2-methoxy-4-morpholinyl)-anthracycline derivatives |
| GB9019934D0 (en) * | 1990-09-12 | 1990-10-24 | Erba Carlo Spa | 2-hydroxy-and 2-acyloxy-4-morpholinyl anthracyclines |
| GB9216962D0 (en) * | 1992-08-11 | 1992-09-23 | Erba Carlo Spa | Therapeutically active naphthalenesulfonic-pyrrolecarboxamido derivatives |
| GB9416007D0 (en) * | 1994-08-08 | 1994-09-28 | Erba Carlo Spa | Anthracyclinone derivatives |
| US6489346B1 (en) * | 1996-01-04 | 2002-12-03 | The Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of using same |
| US6645988B2 (en) * | 1996-01-04 | 2003-11-11 | Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of using same |
| US6699885B2 (en) * | 1996-01-04 | 2004-03-02 | The Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and methods of using same |
| US5840737A (en) | 1996-01-04 | 1998-11-24 | The Curators Of The University Of Missouri | Omeprazole solution and method for using same |
| US5948896A (en) * | 1997-08-13 | 1999-09-07 | Gem Pharmaceuticals | Processes for preparing 13-deoxy anthracycline derivatives |
| US5942605A (en) * | 1998-03-03 | 1999-08-24 | Gem Pharmaceuticals, Inc. | 5-imino-13-deoxy anthracycline derivatives, their uses, and processes for preparing them |
| KR20020008297A (ko) * | 2000-07-21 | 2002-01-30 | 채문식 | 안스라사이클린계 항생물질 도노마이신을 이용한식물병방제용 살균제 |
| US20040006111A1 (en) * | 2002-01-25 | 2004-01-08 | Kenneth Widder | Transmucosal delivery of proton pump inhibitors |
| WO2004073654A2 (en) * | 2003-02-20 | 2004-09-02 | Santarus, Inc. | A novel formulation, omeprazole antacid complex-immediate release for rapid and sustained supression of gastric acid |
| US7053191B2 (en) * | 2003-05-21 | 2006-05-30 | Solux Corporation | Method of preparing 4-R-substituted 4-demethoxydaunorubicin |
| US8993599B2 (en) | 2003-07-18 | 2015-03-31 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| CA2531566C (en) * | 2003-07-18 | 2013-05-07 | Santarus, Inc. | Pharmaceutical formulation and method for treating acid-caused gastrointestinal disorders |
| JP2006528181A (ja) * | 2003-07-18 | 2006-12-14 | サンタラス インコーポレイティッド | 酸分泌を阻害するために有用な薬学的製剤ならびにそれらを作製および使用する方法 |
| US20070292498A1 (en) * | 2003-11-05 | 2007-12-20 | Warren Hall | Combinations of proton pump inhibitors, sleep aids, buffers and pain relievers |
| US8815916B2 (en) | 2004-05-25 | 2014-08-26 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| US8906940B2 (en) | 2004-05-25 | 2014-12-09 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| US7353034B2 (en) | 2005-04-04 | 2008-04-01 | X One, Inc. | Location sharing and tracking using mobile phones or other wireless devices |
| US20090092658A1 (en) * | 2007-10-05 | 2009-04-09 | Santarus, Inc. | Novel formulations of proton pump inhibitors and methods of using these formulations |
| US8357785B2 (en) * | 2008-01-08 | 2013-01-22 | Solux Corporation | Method of aralkylation of 4′-hydroxyl group of anthracylins |
| US8846882B2 (en) | 2011-04-29 | 2014-09-30 | Synbias Pharma Ag | Method of producing 4-demethoxydaunorubicin |
| RU2666356C2 (ru) * | 2013-04-29 | 2018-09-07 | НЕРВИАНО МЕДИКАЛ САЙЕНСИЗ С.р.л. | Новые производные морфолинилантрациклина |
| JP6785780B2 (ja) * | 2014-11-05 | 2020-11-18 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | 官能基化モルホリニルアントラサイクリン誘導体 |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE905014C (de) * | 1944-09-23 | 1954-02-25 | Cassella Farbwerke Mainkur Ag | Verfahren zum Ersatz der Diazogruppe durch Wasserstoff |
| US3803124A (en) | 1968-04-12 | 1974-04-09 | Farmaceutici It Soc | Process for the preparation of adriamycin and adriamycinone and adriamycin derivatives |
| GB1467383A (en) * | 1974-06-12 | 1977-03-16 | Farmaceutici Italia | Daunomycin analogues |
| GB1500421A (en) * | 1975-01-22 | 1978-02-08 | Farmaceutici Italia | Optically active anthracyclinones |
| GB1511559A (en) | 1975-09-26 | 1978-05-24 | Farmaceutici Italia | Anthracycline glycosides |
| US4021457A (en) * | 1975-11-18 | 1977-05-03 | Research Corporation | Intermediates for polycyclic quinonoid antibiotics |
| US4012448A (en) * | 1976-01-15 | 1977-03-15 | Stanford Research Institute | Synthesis of adriamycin and 7,9-epiadriamycin |
| GB1509875A (en) | 1976-06-14 | 1978-05-04 | Farmaceutici Italia | Optically active anthracyclinones and anthracycline glycosides |
| GB1567456A (en) * | 1976-11-16 | 1980-05-14 | Farmaceutici Italia | Daunomycin derivatives |
| US4109076A (en) * | 1977-09-08 | 1978-08-22 | Sri International | 5-iminodaunomycin |
| US4348388A (en) * | 1980-04-02 | 1982-09-07 | G.D. Searle & Co. | 11-Amino-11-deoxydaunorubicin and analogs |
| EP0051280B1 (en) * | 1980-11-01 | 1984-07-11 | FARMITALIA CARLO ERBA S.p.A. | Anthracycline glycosides, process for the preparation thereof, intermediate compounds and their preparation and pharmaceutical compositions |
| US4413120A (en) * | 1981-04-06 | 1983-11-01 | Purdue Research Foundation | Process for producing acosamine, daunosamine, 1-thioacosamine and related compounds |
| IT1168014B (it) * | 1981-08-05 | 1987-05-20 | Erba Farmitalia | Forme farmaceutiche a cessione protratta |
| US4563444A (en) * | 1982-05-26 | 1986-01-07 | Farmitalia Carlo Erba S.P.A. | Anthracycline glycosides, use and compositions containing same |
| US4448724A (en) * | 1982-12-20 | 1984-05-15 | The Trustees Of The University Of Pennsylvania | Synthesis of 4-demethoxydaunomycinone |
| WO1985001726A1 (en) * | 1983-10-19 | 1985-04-25 | The University Of Melbourne | Carminomycinone precursors and analogues and derivatives thereof |
| US4564674A (en) * | 1983-10-31 | 1986-01-14 | Sagami Chemical Research Center | Process for an anthracycline derivative, and an anthracyclinone derivative useful for the process |
| US4591637A (en) * | 1985-01-17 | 1986-05-27 | Sri International | Open chain-morpholino adriamycins |
| GB8617742D0 (en) * | 1986-07-21 | 1986-08-28 | Erba Farmitalia | 6-amino anthracyclines |
| GB8803301D0 (en) * | 1988-02-12 | 1988-03-09 | Erba Carlo Spa | Process for preparation of 4-demethoxy-daunomycinone aglycone of 4-demethoxy-daunorubicin |
-
1988
- 1988-04-14 NZ NZ224252A patent/NZ224252A/xx unknown
- 1988-04-15 YU YU75988A patent/YU46455B/sh unknown
- 1988-04-15 SI SI8810759A patent/SI8810759A8/sl not_active IP Right Cessation
- 1988-04-15 AU AU14695/88A patent/AU600816B2/en not_active Ceased
- 1988-04-15 IL IL86088A patent/IL86088A/xx not_active IP Right Cessation
- 1988-04-18 HU HU881983A patent/HU200188B/hu not_active IP Right Cessation
- 1988-04-18 FI FI881792A patent/FI89263C/fi active IP Right Grant
- 1988-04-18 HU HU881983A patent/HU202810B/hu not_active IP Right Cessation
- 1988-04-18 DK DK210688A patent/DK170405B1/da not_active IP Right Cessation
- 1988-04-19 CS CS882658A patent/CS270585B2/cs not_active IP Right Cessation
- 1988-04-19 IE IE117188A patent/IE63510B1/en not_active IP Right Cessation
- 1988-04-19 PT PT87270A patent/PT87270B/pt not_active IP Right Cessation
- 1988-04-19 ZA ZA882732A patent/ZA882732B/xx unknown
- 1988-04-19 KR KR1019880004424A patent/KR880012627A/ko not_active Ceased
- 1988-04-20 ES ES91100002T patent/ES2093034T3/es not_active Expired - Lifetime
- 1988-04-20 CA CA000564613A patent/CA1315775C/en not_active Expired - Fee Related
- 1988-04-20 SU SU884355593A patent/SU1614764A3/ru active
- 1988-04-20 ES ES88303561T patent/ES2042737T3/es not_active Expired - Lifetime
- 1988-04-20 AT AT88303561T patent/ATE83239T1/de not_active IP Right Cessation
- 1988-04-20 EP EP91100002A patent/EP0426653B1/en not_active Expired - Lifetime
- 1988-04-20 JP JP63098032A patent/JP2651414B2/ja not_active Expired - Fee Related
- 1988-04-20 NO NO881710A patent/NO168702C/no not_active IP Right Cessation
- 1988-04-20 MY MYPI88000396A patent/MY103365A/en unknown
- 1988-04-20 DE DE8888303561T patent/DE3876482T2/de not_active Expired - Fee Related
- 1988-04-20 DE DE3855480T patent/DE3855480T2/de not_active Expired - Fee Related
- 1988-04-20 CN CN88102182A patent/CN1022038C/zh not_active Expired - Fee Related
- 1988-04-20 AT AT91100002T patent/ATE141251T1/de not_active IP Right Cessation
- 1988-04-20 EP EP88303561A patent/EP0288268B1/en not_active Expired - Lifetime
- 1988-10-27 CS CS887117A patent/CS270596B2/cs not_active IP Right Cessation
- 1988-11-04 SU SU884356729A patent/SU1729294A3/ru active
-
1989
- 1989-05-08 YU YU94089A patent/YU46489B/sh unknown
- 1989-11-01 US US07/430,149 patent/US4965351A/en not_active Expired - Lifetime
-
1990
- 1990-01-09 US US07/462,549 patent/US4985548A/en not_active Expired - Lifetime
- 1990-05-25 AU AU55916/90A patent/AU621222B2/en not_active Ceased
-
1991
- 1991-11-05 CA CA000616216A patent/CA1318665C/en not_active Expired - Fee Related
-
1992
- 1992-09-12 CN CN92110559A patent/CN1024545C/zh not_active Expired - Fee Related
- 1992-09-18 MY MYPI92001675A patent/MY104645A/en unknown
- 1992-10-02 HR HRP-940/89A patent/HRP920920B1/xx not_active IP Right Cessation
- 1992-10-02 HR HR920898A patent/HRP920898B1/xx not_active IP Right Cessation
-
1993
- 1993-02-08 PT PT101194A patent/PT101194B/pt not_active IP Right Cessation
- 1993-02-25 GR GR930400400T patent/GR3007163T3/el unknown
-
1994
- 1994-09-12 DK DK199401046A patent/DK174561B1/da not_active IP Right Cessation
-
1996
- 1996-09-12 GR GR960402354T patent/GR3021004T3/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CS270596B2 (en) | Method of 4-demethoxyanthracycline derivatives production | |
| EP0399330A1 (de) | Modifiziertes Phosphoramidit-Verfahren zur Herstellung von modifizierten Nukleinsäuren | |
| EP0240264A2 (en) | Improved process for preparing macrolide derivatives | |
| JP2009513623A (ja) | 塩酸ジェムシタビンの改良された製造方法 | |
| HU188143B (en) | Process for producing 4-comma above-deoxy-daunorubicin | |
| KR100351325B1 (ko) | 에토포시드포스페이트와에토포시드를제조하는방법 | |
| EP0254484A2 (en) | 6-Amino anthracyclines, process for their preparation and use thereof | |
| CS273198B2 (en) | Method of 4-demethoxydaunomycinone production | |
| Takeuchi et al. | Stereoselective glycosylation of thioglycosides promoted by respective combinations of N-iodo-or N-bromosuccinimide and trityl tetrakis (pentafluorophenyl) borate. Application to one-pot sequential synthesis of trisaccharide | |
| DE69106459T2 (de) | 2-Acyloxy-4-morpholinyl-Anthracyclin. | |
| EP0286926A2 (de) | Semisynthetische Rhodomycine, Verfahren zu ihrer Herstellung und ihre Verwendung als Zytostatika | |
| RU2204564C2 (ru) | Способ получения производного дезоксиуридина | |
| DE4126475B4 (de) | 13-Dihydro-3'-(2-Alkoxy-4-morpholinyl)anthracycline, Verfahren zu deren Herstellung, deren Verwendung und diese enthaltende Zusammensetzungen | |
| EP1029867A2 (en) | Process for the preparation of organic azides | |
| SI8910940A8 (sl) | Postopek za pridobivanje 4-demetoksi-antraciklinonov | |
| JPH09249681A (ja) | ６−ｏ−（２−アセトアミドエチルホスホニル）−ｄ−マンノピラノシド誘導体、及びその製造法 | |
| CZ20033442A3 (cs) | Způsob výroby 7-ethyl-10-hydroxykamptothecinu | |
| JPH0531559B2 (cs) | ||
| EP0131232A1 (en) | Stereoselective process for the preparation of anthracycline derivatives | |
| IE930184L (en) | 4-demethoxy-4-amino-anthracyclines | |
| DE3306505C2 (de) | 4-Desmethoxy-13-dihydro-daunorubicin, Verfahren zu dessen Herstellung und diese Verbindung enthaltende Arzneimittel | |
| EP0394908A1 (de) | Verfahren zur Herstellung von Glucosaminyl-epi-podo-phyllotoxin-Derivaten | |
| KR20030033819A (ko) | 2'-플루오로-5-메틸-β-엘-아라비노푸라노실유리딘의 황유도체 | |
| CS235540B2 (cs) | Způsob výroby nových derivátů glykosidů anthracyklinu | |
| JPS6118558B2 (cs) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| IF00 | In force as of 2000-06-30 in czech republic | ||
| MM4A | Patent lapsed due to non-payment of fee |
Effective date: 20040419 |