JP5140583B2 - 4β−アミノ−4’−デメチル−4−デゾキシポドフィロトキシンの調製方法 - Google Patents
4β−アミノ−4’−デメチル−4−デゾキシポドフィロトキシンの調製方法 Download PDFInfo
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- JP5140583B2 JP5140583B2 JP2008521967A JP2008521967A JP5140583B2 JP 5140583 B2 JP5140583 B2 JP 5140583B2 JP 2008521967 A JP2008521967 A JP 2008521967A JP 2008521967 A JP2008521967 A JP 2008521967A JP 5140583 B2 JP5140583 B2 JP 5140583B2
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- JP
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- Prior art keywords
- acid
- demethyl
- structural formula
- halogenoacetamide
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- 238000000034 method Methods 0.000 title claims abstract description 54
- 238000002360 preparation method Methods 0.000 title description 12
- 239000002253 acid Substances 0.000 claims abstract description 47
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims abstract description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000003960 organic solvent Substances 0.000 claims abstract description 17
- 239000000203 mixture Substances 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
- 239000012429 reaction media Substances 0.000 claims description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 11
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 8
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 7
- 229910052740 iodine Inorganic materials 0.000 claims description 7
- FOVRGQUEGRCWPD-UHFFFAOYSA-N (5aR)-9t-beta-D-Glucopyranosyloxy-5t-(4-hydroxy-3,5-dimethoxy-phenyl)-(5ar,8at)-5,8,8a,9-tetrahydro-5aH-furo[3',4';6,7]naphtho[2,3-d][1,3]dioxol-6-on Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(OC3C(C(O)C(O)C(CO)O3)O)C3C2C(OC3)=O)=C1 FOVRGQUEGRCWPD-UHFFFAOYSA-N 0.000 claims description 6
- YVCVYCSAAZQOJI-JHQYFNNDSA-N 4'-demethylepipodophyllotoxin Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YVCVYCSAAZQOJI-JHQYFNNDSA-N 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 150000004292 cyclic ethers Chemical class 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000011630 iodine Substances 0.000 claims description 4
- 238000001308 synthesis method Methods 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 description 40
- 229960000583 acetic acid Drugs 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 239000012362 glacial acetic acid Substances 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 150000001540 azides Chemical class 0.000 description 6
- 238000003776 cleavage reaction Methods 0.000 description 6
- 230000007017 scission Effects 0.000 description 6
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 5
- 238000011097 chromatography purification Methods 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000001226 reprecipitation Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- -1 amino compound Chemical class 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 3
- GVLGAFRNYJVHBC-UHFFFAOYSA-N hydrate;hydrobromide Chemical compound O.Br GVLGAFRNYJVHBC-UHFFFAOYSA-N 0.000 description 3
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical class COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 230000001093 anti-cancer Effects 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000002360 explosive Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- 229960001237 podophyllotoxin Drugs 0.000 description 2
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- YJGVMLPVUAXIQN-LGWHJFRWSA-N (5s,5ar,8ar,9r)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-LGWHJFRWSA-N 0.000 description 1
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 1
- VODKOOOHHCAWFR-UHFFFAOYSA-N 2-iodoacetonitrile Chemical compound ICC#N VODKOOOHHCAWFR-UHFFFAOYSA-N 0.000 description 1
- 0 COc(cc([C@@]([C@]([C@@](CO1)[C@@](c2c3)NC(C*)=O)C1=O)c2cc1c3OCO1)cc1OC)c1O Chemical compound COc(cc([C@@]([C@]([C@@](CO1)[C@@](c2c3)NC(C*)=O)C1=O)c2cc1c3OCO1)cc1OC)c1O 0.000 description 1
- OYRQNWXYGUSVJC-LGWHJFRWSA-N COc1cc([C@@H]([C@H]([C@H](CO2)[C@@H](c3c4)N)C2=O)c3cc2c4OCO2)cc([O](C)C)c1O Chemical compound COc1cc([C@@H]([C@H]([C@H](CO2)[C@@H](c3c4)N)C2=O)c3cc2c4OCO2)cc([O](C)C)c1O OYRQNWXYGUSVJC-LGWHJFRWSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 239000013626 chemical specie Substances 0.000 description 1
- 238000011210 chromatographic step Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- COCAUCFPFHUGAA-MGNBDDOMSA-N n-[3-[(1s,7s)-5-amino-4-thia-6-azabicyclo[5.1.0]oct-5-en-7-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound C=1C=C(F)C([C@@]23N=C(SCC[C@@H]2C3)N)=CC=1NC(=O)C1=CC=C(Cl)C=N1 COCAUCFPFHUGAA-MGNBDDOMSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003511 tertiary amides Chemical class 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- XQKBFQXWZCFNFF-UHFFFAOYSA-K triiodosamarium Chemical compound I[Sm](I)I XQKBFQXWZCFNFF-UHFFFAOYSA-K 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Telephone Set Structure (AREA)
Description
Claims (18)
- 純粋弱酸がR−COOHという構造式5のカルボン酸である(式中Rは水素またはC1〜C2のアルキル基を表わす)ことを特徴とする、請求項1に記載の方法。
- 段階a)に際して、反応媒質が60〜100℃の間に含まれる温度に加熱されることを特徴とする、請求項1または2に記載の方法。
- 段階a)に際して、4β−ハロゲノアセトアミド−4’−デメチル−4−デゾキシポドフィロトキシンをチオ尿素の添加前に純粋弱酸と接触させることを特徴とする、請求項1〜3のいずれか一つに記載の方法。
- 段階a)の反応時間が1〜3時間の間に含まれることを特徴とする、請求項1〜4のいずれか一つに記載の方法。
- 段階i)に際して、反応媒質が60〜100℃の間に含まれる温度に加熱されることを特徴とする、請求項6に記載の方法。
- 段階i)に際して、4β−ハロゲノアセトアミド−4’−デメチル−4−デゾキシポドフィロトキシンをチオ尿素の添加前に、酸、水および有機溶媒の混合物と接触させることを特徴とする、請求項6または7に記載の方法。
- 有機溶媒が水溶性有機溶媒であることを特徴とする、請求項6〜8のいずれか一つに記載の方法。
- 溶媒がエタノールであることを特徴とする、請求項9に記載の方法。
- 酸が強酸であることを特徴とする、請求項10に記載の方法。
- 酸が弱酸であることを特徴とする、請求項6〜10のいずれか一つに記載の方法。
- エタノールまたはジオキサンまたはN,N−ジメチルアセトアミド、ジメチルホルムアミド、N−メチルピロリドン/水/酢酸の体積比が、5/1/1であることを特徴とする、請求項12に記載の方法。
- 4β−ハロゲノアセトアミド−4’−デメチル−4−デゾキシポドフィロトキシンとチオ尿素の間のモル比が0.5〜1の間に含まれることを特徴とする、請求項1〜13のいずれか一つに記載の方法。
- 水溶性有機溶媒が、環状エーテル、アルコール、N,N−ジメチルアセトアミド、ジメチルホルムアミド、N−メチルピロリドンから成る群から選択されることを特徴とする、請求項9に記載の方法。
- 強酸が、塩酸、硫酸およびリン酸から成る群から選択されることを特徴とする、請求項11に記載の方法。
- 弱酸が、R−COOHという構造式5のカルボン酸(式中Rは水素またはC 1 〜C 2 のアルキル基を表わす)であることを特徴とする、請求項12に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR0507642A FR2888849B1 (fr) | 2005-07-19 | 2005-07-19 | Procede de preparation de la 4b-amino-4'-demethyl-4-desoxypodophyllotoxine |
FR0507642 | 2005-07-19 | ||
PCT/EP2006/064420 WO2007010007A1 (fr) | 2005-07-19 | 2006-07-19 | PROCEDE DE PREPARATION DE LA 4β-AMINO-4'-DEMETHYL-4-DESOXYPODOPHYLLOTOXINE |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009501764A JP2009501764A (ja) | 2009-01-22 |
JP5140583B2 true JP5140583B2 (ja) | 2013-02-06 |
Family
ID=36035759
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008521967A Expired - Fee Related JP5140583B2 (ja) | 2005-07-19 | 2006-07-19 | 4β−アミノ−4’−デメチル−4−デゾキシポドフィロトキシンの調製方法 |
Country Status (30)
Country | Link |
---|---|
US (2) | US7932406B2 (ja) |
EP (1) | EP1907396B1 (ja) |
JP (1) | JP5140583B2 (ja) |
KR (1) | KR101357664B1 (ja) |
CN (1) | CN101223176B (ja) |
AT (1) | ATE414707T1 (ja) |
AU (1) | AU2006271645B2 (ja) |
BR (1) | BRPI0613418A2 (ja) |
CA (1) | CA2616064C (ja) |
CY (1) | CY1108804T1 (ja) |
DE (1) | DE602006003769D1 (ja) |
DK (1) | DK1907396T3 (ja) |
ES (1) | ES2317561T3 (ja) |
FR (1) | FR2888849B1 (ja) |
HK (1) | HK1114101A1 (ja) |
HR (1) | HRP20090103T3 (ja) |
IL (1) | IL188716A0 (ja) |
MA (1) | MA29690B1 (ja) |
MX (1) | MX2008000961A (ja) |
NO (1) | NO20080812L (ja) |
NZ (1) | NZ565923A (ja) |
PL (1) | PL1907396T3 (ja) |
PT (1) | PT1907396E (ja) |
RS (1) | RS50782B (ja) |
RU (1) | RU2405787C2 (ja) |
SI (1) | SI1907396T1 (ja) |
TN (1) | TNSN08030A1 (ja) |
UA (1) | UA90530C2 (ja) |
WO (1) | WO2007010007A1 (ja) |
ZA (1) | ZA200801577B (ja) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2637886A (en) * | 1950-04-06 | 1953-05-12 | Walther Trautwein | Slide fastener |
FR2888849B1 (fr) * | 2005-07-19 | 2007-10-05 | Pierre Fabre Medicament Sa | Procede de preparation de la 4b-amino-4'-demethyl-4-desoxypodophyllotoxine |
FR2921368B1 (fr) * | 2007-09-25 | 2012-10-12 | Pf Medicament | Nouveau procede de synthese de derives anticancereux de (poly) aminoalkylaminoacetamide d'epipodophyllotoxine. |
FR2935143B1 (fr) * | 2008-08-19 | 2010-12-03 | Pf Medicament | Nouveaus derives (poly)aminoalkylaminoalkylamides, alkyl-urees, ou alkyl-sulfonamides d'epipodophyllotoxine, leur procede de preparation et leur application en therapeuthique comme agent cancereux |
EP2448911A1 (en) | 2009-06-29 | 2012-05-09 | Merz Pharma GmbH & Co. KGaA | Method of preparing 1-chloroacetamido-1,3,3,5,5-pentamethylcyclohexane |
EP2448909B1 (en) * | 2009-06-29 | 2013-05-01 | Merz Pharma GmbH & Co. KGaA | Method of preparing 1-amino-1,3,3,5,5-pentamethylcyclohexane |
CA2765609A1 (en) * | 2009-06-29 | 2011-01-06 | Merz Pharma Gmbh & Co. Kgaa | Method of preparing neramexane |
CN110294764B (zh) * | 2019-07-15 | 2021-04-20 | 中国科学院兰州化学物理研究所 | 一种偶氮键连接的鬼臼毒素衍生物及其制备方法 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS61126095A (ja) * | 1984-11-26 | 1986-06-13 | Fuji Yakuhin Kogyo Kk | 新規グルコサミン誘導体 |
JPS62215583A (ja) * | 1986-03-14 | 1987-09-22 | Takeda Chem Ind Ltd | ピラゾリジノン誘導体およびその製造法 |
US5332811A (en) * | 1989-09-12 | 1994-07-26 | The University Of North Carolina At Chapel Hill | Etopside analogs |
WO2004073375A2 (en) | 2003-02-18 | 2004-09-02 | Ranbaxy Laboratories Limited | Podophyllotoxin derivatives as antitumor agents |
FR2869035B1 (fr) * | 2004-04-16 | 2006-07-14 | Pierre Fabre Medicament Sa | Derives (poly)aminoalkylaminoacetamide d'epipodophyllotoxine leur procede de preparation et leurs applications en therapeutique comme agent anticancereux |
FR2888849B1 (fr) * | 2005-07-19 | 2007-10-05 | Pierre Fabre Medicament Sa | Procede de preparation de la 4b-amino-4'-demethyl-4-desoxypodophyllotoxine |
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