HRP920920A2 - Postupak za dobivanje 4-demetoksi-antraciklinona - Google Patents
Postupak za dobivanje 4-demetoksi-antraciklinona Download PDFInfo
- Publication number
- HRP920920A2 HRP920920A2 HRP920920AA HRP920920A HRP920920A2 HR P920920 A2 HRP920920 A2 HR P920920A2 HR P920920A A HRP920920A A HR P920920AA HR P920920 A HRP920920 A HR P920920A HR P920920 A2 HRP920920 A2 HR P920920A2
- Authority
- HR
- Croatia
- Prior art keywords
- demethoxy
- daunomycinone
- amino
- xva
- aqueous solution
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 10
- 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
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 235000010288 sodium nitrite Nutrition 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000003756 stirring Methods 0.000 claims description 3
- 238000001704 evaporation Methods 0.000 claims 1
- 230000008020 evaporation Effects 0.000 claims 1
- 238000000605 extraction Methods 0.000 claims 1
- TVZISJTYELEYPI-UHFFFAOYSA-N hypodiphosphoric acid Chemical compound OP(O)(=O)P(O)(O)=O TVZISJTYELEYPI-UHFFFAOYSA-N 0.000 claims 1
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 abstract 2
- 229960000975 daunorubicin Drugs 0.000 abstract 2
- 239000002253 acid Substances 0.000 abstract 1
- 229940045799 anthracyclines and related substance Drugs 0.000 abstract 1
- 229960004679 doxorubicin Drugs 0.000 abstract 1
- 229930182470 glycoside Natural products 0.000 abstract 1
- 150000002338 glycosides Chemical class 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
- 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 description 10
- 150000001875 compounds Chemical class 0.000 description 7
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 4
- 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
- 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
- 239000000243 solution Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 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
- YOFDHOWPGULAQF-UHFFFAOYSA-N Daunomycin-Aglycone Natural products C1C(O)(C(C)=O)CC(O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 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 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000003277 amino group Chemical group 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
- 238000009903 catalytic hydrogenation 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
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
Prijava je izdvojena iz YU prijave P-759/88.
Područje tehnike
Izum je iz područja sinteze organskih spojeva. Oznaka prema Međunarodnoj klasifikaciji patenta je C 07 H 15/252 i A 61K 3/71.
Tehnički problem
Izumom je riješen tehnički problem novog postupka za sintezu poznatog spoja, 4-demetoksi-daunomicinona, korisnog intermedijera iz kojeg se, kondenzacijom s prikladnim šećernim derivatima, dobivaju 4-demetoksi atraciklinski glukozidi.
Stanje tehnike
U osnovnoj prijavi YU P-759/88, iz koje je sadašnja prijava izdvojena, opisan je novi aglikon, 4-demetoksi-4-amino -7-dezoksi-daunomicinon formule:
[image]
kao i postupak za njihovo dobivanje katalitičkom hidrogenacijom tamo opisanog 4-demetoksi-4 benzilamino-7- daunomininona formule:
[image]
Opis rješenja tehničkog problema
Sadašnja prijava se odnosi na postupak kojim se navedeni novi aglikon, 4-demetoksi-4-amino-7-dezoksi-daunomicinon (predstavljen formulom XVa), prevodi u poznate dezamino spojeve.
[image]
(a; R4=H)
(b; R4=OH)
Iz spoja (XVa) se lako dobiva spoj (XVb), u kojem R4 predstavlja hidroksilnu skupinu.
Antriciklinoni formule (XVa) i (XVb) koji u poziciji 4 imaju amino skupinu, pretvaraju se u odgovarajuće dezamino derivate formule:
[image]
(a; R4=H)
(b; R4=OH)
primjenom diazotacije i zatim blage redukcije dobivenih diazonijevih spojeva. Polazni spojevi su 4-demetoksi-4-amino-7-dezoksi-daunomicinon (XVa) i 4-demetoksi-4-amino-duanomicinon (XVb). Uklanjanje 4-amino skupine diazotiranjem i blagom redukcijom daje dobro poznati 4-demetoksi-7-dezoksi-daunomicinon (VIVa) ili 4-demetoksi-daunomicinon (XIVb). Kao što je prikazano u reakcijskoj shemi, diazotiranje se poželjno vrši korištenjem vodene otopine natrijevog nitrita. Blaga redukcija se poželjno vrši korištenjem hipofosforaste kiseline.
[image]
1) vod. otopina Na NO2
2) hipofosforasta kiselina
Spoj formule (XVa), u kojem je R4 vodik, lako se pretvara u spoj formule (XVb) u kojoj je R4 hidroksilna skupina, 4-demetoksi-4-amino-7-dezoksi-daunomicinon (XVa) ili 4-demetoksi-4-amino daunomicinon (XVb) se, poželjno, otopi u 37%-tnoj vodenoj otopini klorovodične kiseline i reagira na temperaturi od 0 do 5°C tijekom jednog sata s vodenom otopinom natrij nitrata, nakon čega se tijekom pet sati na sobnoj temperaturi, uz snažno miješanje, dovodi u kontakt 50%-tnom vodenom otopinom hipofosforaste kiseline. Reakcijska smjesa se zatim ekstrahira metilen dikloridom, pa se otapalo uklanja pod smanjenim pritiskom.
4-demetoksi-7-dezoksi-daunomicinon (XVa) se može prevesti u 4-demetoksi-daunomicinon (XIVb) uvođenjem hidroksilne skupine u poziciju 7. Ovo se može izvršiti bromiranjem u poziciji 7, na primjer s bromom ili N-bromo- sukcinimidom (NBS), nakon čega se obavlja tretman s alkalijem, ili reakcija sa srebrnim acetatom nakon koje slijedi metanoliza dobivenog acetata.
4-demetoksi-daunomicinon (XIVb) je aglikon dobro poznatog i korisnog lijeka 4-demetoksi-daunorubicina.
Primjer 1
Dobivanje 4-demetoksi-7-dezoksi-daunomicinon (XIVa)
1.78 g (5 mmol) 4-demetoksi-4-amino-7-dezoksi-daunomicinon (XVa), otopljenog u 75 ml 37%-tne vodene otopine klorovodične kiseline, hladi se na 0 - 5°C i zatim se dodaje 75 ml vodene otopine koja sadrži 0.6 g natrijevog nitrita. Smjesa se miješa jedan sat na 0 - 5°C. Zatim se dodaje 75 ml 50%-tne vodene otopine hipofosforaste kiseline i smjesa se drži na sobnoj temperaturi, uz snažno miješanje, tijekom pet sati.
Otopina se razblaži s 200 ml vode i ekstrahira se metilen dikloridom. Organski spoj se odvaja, suši preko bezvodnog Na2SO4 i otapalo se uklanja pod smanjenim pritiskom da bi dobio kvantitativni prinos (1.7g) 4-demetoksi- 7-dezoksi- daunomicinon (XVa), koji je analitički uspoređen sa standardnim uzorkom.
Primjer 2
Dobivanje 4-demetoksi-daunomicinona (XIVb)
1.86 g (5 mmol) 4-demetoksi-4-amino-daunomicinona (XVb) se, na način opisan u Primjeru 1, prevodi u odgovarajući 4-demetoksi-daunomicinon (XIVb). Dobiva se 1.8 g spoja (XIVb), koji se analitički uspoređuje sa standardnim uzorkom.
Claims (1)
1. Postupak za dobivanje 4-demetoksi-antraciklona formule (XIVa) ili (XIVb):
[image]
u kojoj R4 predstavlja vodik (XIVa) ili hidroksi (XIVb), naznačen time, što 4-demetoksi-4-amino-7-daunomicinon (XVa) ili 4-demetoksi-4-amino-daunomicinon (XVb):
[image]
u kojoj je R4 predstavlja vodik (XVa) ili hidroksi (XVb), u 37%-tnoj vodenojotopini klorovodične kiseline i na temperaturi od 0 do 5°C, tijekom jednog sata reagira s vodenom otopinom natrijevog nitrita, pa se zatim, tijekom pet sati na sobnojtemperaturi i uz snažno miješanje, tretira 50%-tnom vodenom otopinom hipofosforne kiseline čime se, nakon ekstrakcije smetilen dikloridom i uparavanja otapala pod smanjenim pritiskom,proizvod formule (XVa) ili (XVb) dobiva u kvantitativnom prinosu.
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 |
| YU94089A YU46489B (sh) | 1987-04-21 | 1989-05-08 | Postupak za dobijanje 4-demetoksi-antraciklinona |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HRP920920A2 true HRP920920A2 (hr) | 1994-04-30 |
| HRP920920B1 HRP920920B1 (en) | 1998-08-31 |
Family
ID=26292154
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP-940/89A HRP920920B1 (en) | 1987-04-21 | 1992-10-02 | Method for preparing 4-demethoxy-anthracyclinones |
| HR920898A HRP920898B1 (en) | 1987-04-21 | 1992-10-02 | 4-demethoxy-4-amino-anthracyclines and a process for the preparation thereof |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR920898A HRP920898B1 (en) | 1987-04-21 | 1992-10-02 | 4-demethoxy-4-amino-anthracyclines and a process for the preparation thereof |
Country Status (26)
| Country | Link |
|---|---|
| US (2) | US4965351A (hr) |
| EP (2) | EP0288268B1 (hr) |
| JP (1) | JP2651414B2 (hr) |
| KR (1) | KR880012627A (hr) |
| CN (2) | CN1022038C (hr) |
| AT (2) | ATE141251T1 (hr) |
| AU (2) | AU600816B2 (hr) |
| CA (2) | CA1315775C (hr) |
| CS (2) | CS270585B2 (hr) |
| DE (2) | DE3855480T2 (hr) |
| DK (2) | DK170405B1 (hr) |
| ES (2) | ES2042737T3 (hr) |
| FI (1) | FI89263C (hr) |
| GR (2) | GR3007163T3 (hr) |
| HR (2) | HRP920920B1 (hr) |
| HU (2) | HU202810B (hr) |
| IE (1) | IE63510B1 (hr) |
| IL (1) | IL86088A (hr) |
| MY (2) | MY103365A (hr) |
| NO (1) | NO168702C (hr) |
| NZ (1) | NZ224252A (hr) |
| PT (2) | PT87270B (hr) |
| SI (1) | SI8810759A8 (hr) |
| SU (2) | SU1614764A3 (hr) |
| YU (2) | YU46455B (hr) |
| ZA (1) | ZA882732B (hr) |
Families Citing this family (29)
| 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 |
| US6489346B1 (en) | 1996-01-04 | 2002-12-03 | The 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 |
| US6645988B2 (en) | 1996-01-04 | 2003-11-11 | Curators Of The University Of Missouri | Substituted benzimidazole dosage forms and method of 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 |
| EP1603537A4 (en) * | 2003-02-20 | 2009-11-04 | Santarus Inc | IMMEDIATE RELEASE OF OMEPRAZOLE ANTACIDAL COMPLEX WITH NEW FORMULATION FOR RAPID AND PROLONGED ELIMINATION OF GASTRIC ACID |
| US7053191B2 (en) * | 2003-05-21 | 2006-05-30 | Solux Corporation | Method of preparing 4-R-substituted 4-demethoxydaunorubicin |
| AR045062A1 (es) * | 2003-07-18 | 2005-10-12 | Santarus Inc | Formulaciones farmaceuticas para inhibir la secrecion de acido y metodos para preparar y utilizarlas |
| JP2006528182A (ja) * | 2003-07-18 | 2006-12-14 | サンタラス インコーポレイティッド | 薬学的製剤および酸に起因する消化器疾患の治療法 |
| US8993599B2 (en) | 2003-07-18 | 2015-03-31 | Santarus, Inc. | Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them |
| 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 |
| WO2014177441A1 (en) | 2013-04-29 | 2014-11-06 | Nerviano Medical Sciences S.R.L. | New morpholinyl anthracycline derivatives |
| ES2735375T3 (es) * | 2014-11-05 | 2019-12-18 | Nerviano Medical Sciences Srl | Derivados funcionalizados de morfolinil antraciclina |
Citations (5)
| 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 |
| DE2601785A1 (de) * | 1975-01-22 | 1976-07-29 | Farmaceutici Italia | Optisch aktive anthracyclinone |
| US4012448A (en) * | 1976-01-15 | 1977-03-15 | Stanford Research Institute | Synthesis of adriamycin and 7,9-epiadriamycin |
| US4021457A (en) * | 1975-11-18 | 1977-05-03 | Research Corporation | Intermediates for polycyclic quinonoid antibiotics |
| US4448724A (en) * | 1982-12-20 | 1984-05-15 | The Trustees Of The University Of Pennsylvania | Synthesis of 4-demethoxydaunomycinone |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| GB1511559A (en) | 1975-09-26 | 1978-05-24 | Farmaceutici Italia | Anthracycline glycosides |
| 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 |
| US4366149A (en) * | 1980-11-01 | 1982-12-28 | Erba Farmitalia | Antitumor anthracycline glycosides, their preparation, intermediates therefor, and compositions and use thereof |
| 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 |
| EP0159357B1 (en) * | 1983-10-19 | 1992-09-09 | 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 |
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| 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 |
| DE2601785A1 (de) * | 1975-01-22 | 1976-07-29 | Farmaceutici Italia | Optisch aktive anthracyclinone |
| 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 |
| US4448724A (en) * | 1982-12-20 | 1984-05-15 | The Trustees Of The University Of Pennsylvania | Synthesis of 4-demethoxydaunomycinone |
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| I. L. FINAR: "Organic chemistry", 1954, stranica 493-495, članak XXIV, Longmans, Green and Co., London, GB; "Diazonium salts and their related compounds * |
| TETRAHEDRON, vol.40, br.22, 1984, stranice 4617-4623, Pergamon Press Ltd, GB; K. TAMOTO et al.: "Novel resolution of the anthracyclinone intermediate by the use of (2R, 3R)-(+)-and (2S, 3S)-(-)-1, 4-bis(4-chlorobenzyloxy)-butane-2,3-diol; a simple and efficient synthesis of optically pure 4-demethoxydaunomycinone and 4-demethoxyadriamycinone * |
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