JP4870161B2 - 1,7’−ジメチル−2’−プロピル−2,5’−ビ−1h−ベンゾイミダゾールの調製 - Google Patents
1,7’−ジメチル−2’−プロピル−2,5’−ビ−1h−ベンゾイミダゾールの調製 Download PDFInfo
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- JP4870161B2 JP4870161B2 JP2008521953A JP2008521953A JP4870161B2 JP 4870161 B2 JP4870161 B2 JP 4870161B2 JP 2008521953 A JP2008521953 A JP 2008521953A JP 2008521953 A JP2008521953 A JP 2008521953A JP 4870161 B2 JP4870161 B2 JP 4870161B2
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- triazine
- benzimidazole
- propyl
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- methyl
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- 238000002360 preparation method Methods 0.000 title claims description 7
- ILXRSCZVHSZGCS-UHFFFAOYSA-N 4-methyl-6-(1-methylbenzimidazol-2-yl)-2-propyl-1h-benzimidazole Chemical compound C1=CC=C2N(C)C(C3=CC(C)=C4N=C(NC4=C3)CCC)=NC2=C1 ILXRSCZVHSZGCS-UHFFFAOYSA-N 0.000 title abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- XWAJTVCEILFDGU-UHFFFAOYSA-N 7-methyl-2-propyl-3h-benzimidazole-5-carboxylic acid Chemical compound C1=C(C(O)=O)C=C2NC(CCC)=NC2=C1C XWAJTVCEILFDGU-UHFFFAOYSA-N 0.000 claims abstract description 10
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 7
- 150000003512 tertiary amines Chemical class 0.000 claims abstract description 6
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 230000008878 coupling Effects 0.000 claims abstract description 4
- 238000010168 coupling process Methods 0.000 claims abstract description 4
- 238000005859 coupling reaction Methods 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- GPIQOFWTZXXOOV-UHFFFAOYSA-N 2-chloro-4,6-dimethoxy-1,3,5-triazine Chemical compound COC1=NC(Cl)=NC(OC)=N1 GPIQOFWTZXXOOV-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
- -1 2-chloro-4,6-disubstituted-1,3,5-triazine Chemical class 0.000 claims description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 3
- JKAPWXKZLYJQJJ-UHFFFAOYSA-N 2,4-dichloro-6-methoxy-1,3,5-triazine Chemical compound COC1=NC(Cl)=NC(Cl)=N1 JKAPWXKZLYJQJJ-UHFFFAOYSA-N 0.000 claims description 2
- ACMVCGAZNQJQFJ-UHFFFAOYSA-N 2,4-dichloro-6-phenoxy-1,3,5-triazine Chemical compound ClC1=NC(Cl)=NC(OC=2C=CC=CC=2)=N1 ACMVCGAZNQJQFJ-UHFFFAOYSA-N 0.000 claims description 2
- BLYRMYBCLLKQBV-UHFFFAOYSA-N 2,4-dichloro-6-phenylmethoxy-1,3,5-triazine Chemical compound ClC1=NC(Cl)=NC(OCC=2C=CC=CC=2)=N1 BLYRMYBCLLKQBV-UHFFFAOYSA-N 0.000 claims description 2
- WPAYYYDSSCOEHN-UHFFFAOYSA-N 2-chloro-4,6-diphenoxy-1,3,5-triazine Chemical compound N=1C(OC=2C=CC=CC=2)=NC(Cl)=NC=1OC1=CC=CC=C1 WPAYYYDSSCOEHN-UHFFFAOYSA-N 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 claims description 2
- 239000002798 polar solvent Substances 0.000 claims description 2
- XKDFUXJROYAXAO-UHFFFAOYSA-N 2-chloro-4,6-bis(phenylmethoxy)-1,3,5-triazine Chemical compound N=1C(OCC=2C=CC=CC=2)=NC(Cl)=NC=1OCC1=CC=CC=C1 XKDFUXJROYAXAO-UHFFFAOYSA-N 0.000 claims 1
- AFYMQOIANUAUTJ-UHFFFAOYSA-N 6-(1H-benzimidazol-2-yl)-2-propyl-1H-benzimidazole Chemical compound C(CC)C=1NC2=C(N=1)C=CC(=C2)C1=NC2=C(N1)C=CC=C2 AFYMQOIANUAUTJ-UHFFFAOYSA-N 0.000 claims 1
- 150000004985 diamines Chemical class 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- RPKCLSMBVQLWIN-UHFFFAOYSA-N 2-n-methylbenzene-1,2-diamine Chemical compound CNC1=CC=CC=C1N RPKCLSMBVQLWIN-UHFFFAOYSA-N 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract 1
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 4
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 4
- OOZKQOFEBPDHPA-UHFFFAOYSA-N 2-n-methylbenzene-1,2-diamine;phosphoric acid Chemical compound OP(O)(O)=O.CNC1=CC=CC=C1N OOZKQOFEBPDHPA-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 235000021317 phosphate Nutrition 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 229960005187 telmisartan Drugs 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 150000003918 triazines Chemical class 0.000 description 2
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- LICHZPCMTSRBHH-UHFFFAOYSA-N C(C1=CC=CC=C1)OC1=NC=NC=N1.ClC1=CN=CN=C1 Chemical compound C(C1=CC=CC=C1)OC1=NC=NC=N1.ClC1=CN=CN=C1 LICHZPCMTSRBHH-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000010640 amide synthesis reaction Methods 0.000 description 1
- 150000001556 benzimidazoles Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
1,7'-ジメチル-2'-プロピル-2,5'-ビ-1H-ベンゾイミダゾールは、医薬的な有効成分テルミサルタンの大規模な合成において、中間生成物として使用される。
Ries et al.,J.Med.Chem.(1993)、36(25)、4040-51には、リン酸の存在下で、2-プロピル-4-メチル-1H-ベンゾイミダゾール-6-カルボン酸とN-メチル-o-フェニレン-ジアミンとを反応させることによる、1,7'-ジメチル-2'-プロピル-2,5'-ビ-1H-ベンゾイミダゾールの調製について記載されている。
本発明は、式(I)の1,7'-ジメチル-2'-プロピル-2,5'-ビ-1H-ベンゾイミダゾールの調製のための別法に関する。
a) 1,3,5-トリアジン及び第三アミンによる2-プロピル-4-メチル-1H-ベンゾイミダゾール-6-カルボン酸又はその塩の活性化、
b) 活性カルボン酸とN-メチル-o-フェニレン-ジアミン又はその塩の結合による、対応するアミドの形成及び
c) 加熱による得られたアミドの環化による、1,7'-ジメチル-2'-プロピル-2,5'-ビ-1H-ベンゾイミダゾールの形成。精製段階は段階(b)及び(c)の間に挿入しうる。1,7'-ジメチル-2'-プロピル-2,5'-ビ-1H-ベンゾイミダゾールは結晶化により精製する。
a) 中温を使用し、好ましくは60℃より低く、
b) 結合反応物としての酸化リンの使用を避け、
c) 環化のためのメタンスルホン酸の使用を避ける。
実施例1:
2-クロロ-4,6-ジメトキシ-1,3,5-トリアジンの存在下での反応−変形1
2-クロロ-4,6-ジメトキシ-1,3,5-トリアジン14.49gをメタノール75mLに入れ、ほぼ0℃まで攪拌しながら冷却した。N-メチルモルホリン9.07mLを5分間に渡り滴状で0℃にて加え、さらに40分間0〜5℃にて攪拌した。2-プロピル-4-メチル-1H-ベンゾイミダゾール-6-カルボン酸16.37gを透明な溶液に加え、これをメタノール30mLで0℃にてすすいだ。2時間後0℃にて、2時間後10℃にて、N-メチル-o-フェニレン-ジアミンリン酸塩15gを加え、混合物をメタノール7.5mLですすぎ、懸濁液をさらに30分間10℃にて攪拌し、その後さらに2時間還流温度にて攪拌した。混合物を室温に冷めるまでゆっくり攪拌しながら一晩放置した。結果得られた結晶スラリーを5℃まで冷却し、二時間ゆっくり攪拌した後、吸引濾過した。結晶をよく冷えたメタノールで洗浄した。
収率:16.91g(理論の69.9%)
HPLC:77.9%
2-クロロ-4,6-ジメトキシ-1,3,5-トリアジンの存在下での反応−変形2
メタノール20mL中の2-クロロ-4.6-ジメトキシ-1,3,5-トリアジン0.88gを取り、ほぼ0℃まで攪拌しながら冷却した。N-メチルモルホリン0.55mLを滴状で0〜5℃にて加え、混合物をさらに40分間0〜5℃にて攪拌した。2-プロピル-4-メチル-1H-ベンゾイミダゾール-6-カルボン酸1.09gを透明な溶液に加え、次にこれをメタノール10mLで0℃にてすすいだ。1時間後0℃にて、1時間後室温にて、N-メチル-o-フェニレン-ジアミンリン酸塩1.0gを加え、懸濁液を一晩攪拌し、その後2時間攪拌しながら還流した。混合物を室温に冷めるまでゆっくり攪拌しながら一晩放置した。結晶を吸引濾過し、メタノールで洗浄した。
収率:0.55g(理論の34.2%)
HPLC:97.7%
2-クロロ-4,6-ジメトキシ-1,3,5-トリアジンの存在下での反応−変形3
2-プロパノール20mL中の2-クロロ-4,6-ジメトキシ-1,3,5-トリアジン0.97gを取り出し、ほぼ0℃まで攪拌しながら冷却した。N-メチルモルホリン0.6mLを滴状で0℃にて加え、混合物をさらに40分間0〜5℃にて攪拌した。2-プロピル-4-メチル-1H-ベンゾイミダゾール-6-カルボン酸1.09gを濃厚な白い懸濁液に加え、2-プロパノール10mLで0℃にてすすいだ。0℃にて1時間後、混合物を室温に達成させ、さらに幾らか攪拌した。2時間後、反応混合物はほとんど溶解状態である。その後、混合物を55℃まで熱し、75分間の間に渡って、N-メチル-o-フェニレン-ジアミンリン酸塩1.0gを加え、混合物をさらに10時間攪拌した。その後混合物を取り置き、一晩そのままに放置した。結晶を吸引濾過し、2-プロパノールで洗浄した。
収率:0.57g(理論の35.4%)
HPLC:96.8%
Claims (5)
- 結合及び環化が2-クロロ-4,6-二置換型-1,3,5-トリアジンを用いて達成されることを特徴とする、請求項1記載の方法。
- 結合及び環化が、
2,4,6-トリクロロ-1,3,5-トリアジン、
2-クロロ-4,6-ジフェノキシ-1,3,5-トリアジン、
2-クロロ-4,6-ジベンジルオキシ-1,3,5-トリアジン、
2-クロロ-4,6-ジメトキシ-1,3,5-トリアジン、
2,4-ジクロロ-6-フェノキシ-1,3,5-トリアジン、
2,4-ジクロロ-6-ベンジルオキシ-1,3,5-トリアジン又は
2,4-ジクロロ-6-メトキシ-1,3,5-トリアジン
を用いて達成されることを特徴とする、請求項1記載の方法。 - N,N-ジメチルホルムアミド、N,N-ジメチルアセトアミド、ジメチルスルホキシド、メタノール、エタノール又は2-プロパノールを極性溶剤として用いることを特徴とする、請求項1記載の方法。
- 30%より多い収率を達成することを特徴とする、請求項1記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102005034279A DE102005034279A1 (de) | 2005-07-22 | 2005-07-22 | Herstellung von 1,7'-Dimethyl-2'-propyl-2,5'-bi-1H-benzimidazol |
DE102005034279.5 | 2005-07-22 | ||
PCT/EP2006/064320 WO2007009967A1 (de) | 2005-07-22 | 2006-07-17 | Herstellung von 1,7′-dimethyl-2′-propyl-2,5′-bi-1h-benzimidazol |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2009502762A JP2009502762A (ja) | 2009-01-29 |
JP4870161B2 true JP4870161B2 (ja) | 2012-02-08 |
Family
ID=37075227
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008521953A Active JP4870161B2 (ja) | 2005-07-22 | 2006-07-17 | 1,7’−ジメチル−2’−プロピル−2,5’−ビ−1h−ベンゾイミダゾールの調製 |
Country Status (8)
Country | Link |
---|---|
US (1) | US7608722B2 (ja) |
EP (1) | EP1912951B1 (ja) |
JP (1) | JP4870161B2 (ja) |
AT (1) | ATE454376T1 (ja) |
CA (1) | CA2615746C (ja) |
DE (2) | DE102005034279A1 (ja) |
ES (1) | ES2335692T3 (ja) |
WO (1) | WO2007009967A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006044648A1 (en) * | 2004-10-15 | 2006-04-27 | Teva Pharmaceutical Industries Ltd. | Process for preparing telmisartan |
US8362269B2 (en) * | 2008-05-02 | 2013-01-29 | Boehringer Ingelheim International Gmbh | Preparation of 1,7′-dimethyl-2′-propyl-2,5′-bi-1H-benzimidazole |
WO2012028925A2 (en) | 2010-09-03 | 2012-03-08 | Ogene Systems (I) Pvt Ltd | An improved process for the preparation of telmisartan |
CN102557964A (zh) * | 2010-12-09 | 2012-07-11 | 宜昌长江药业有限公司 | 一种n-甲基邻苯二胺(盐)及其同分异构体的合成方法 |
CN111372924B (zh) | 2017-11-13 | 2023-09-19 | 埃科莱布美国股份有限公司 | 用于大规模制造2-取代的苯并咪唑的新颖一锅式均质方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10201725A1 (de) | 2002-01-18 | 2003-08-14 | Boehringer Ingelheim Pharma | Verfahren zur Herstellung und Reinigung von 1,7'-Dimethyl-2'-propyl-2,5'-bi-1H-benzimidazol |
-
2005
- 2005-07-22 DE DE102005034279A patent/DE102005034279A1/de not_active Withdrawn
-
2006
- 2006-07-12 US US11/485,153 patent/US7608722B2/en active Active
- 2006-07-17 EP EP06764180A patent/EP1912951B1/de active Active
- 2006-07-17 JP JP2008521953A patent/JP4870161B2/ja active Active
- 2006-07-17 AT AT06764180T patent/ATE454376T1/de active
- 2006-07-17 DE DE502006005865T patent/DE502006005865D1/de active Active
- 2006-07-17 CA CA2615746A patent/CA2615746C/en not_active Expired - Fee Related
- 2006-07-17 ES ES06764180T patent/ES2335692T3/es active Active
- 2006-07-17 WO PCT/EP2006/064320 patent/WO2007009967A1/de not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
EP1912951B1 (de) | 2010-01-06 |
ATE454376T1 (de) | 2010-01-15 |
EP1912951A1 (de) | 2008-04-23 |
WO2007009967A1 (de) | 2007-01-25 |
US7608722B2 (en) | 2009-10-27 |
CA2615746C (en) | 2014-05-13 |
US20070037986A1 (en) | 2007-02-15 |
DE502006005865D1 (de) | 2010-02-25 |
ES2335692T3 (es) | 2010-03-31 |
JP2009502762A (ja) | 2009-01-29 |
DE102005034279A1 (de) | 2007-01-25 |
CA2615746A1 (en) | 2007-01-25 |
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