SI21507A - Postopek za pripravo spojin z ace inhibitornim delovanjem - Google Patents
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- SI21507A SI21507A SI200300123A SI200300123A SI21507A SI 21507 A SI21507 A SI 21507A SI 200300123 A SI200300123 A SI 200300123A SI 200300123 A SI200300123 A SI 200300123A SI 21507 A SI21507 A SI 21507A
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- compounds
- ace inhibitory
- activated
- inhibitory activity
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- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 150000001875 compounds Chemical class 0.000 title claims abstract description 8
- 230000000694 effects Effects 0.000 title abstract 2
- 230000005764 inhibitory process Effects 0.000 title abstract 2
- -1 hexafluoro phosphate Chemical compound 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 6
- 229910019142 PO4 Inorganic materials 0.000 claims abstract description 4
- 150000001412 amines Chemical class 0.000 claims abstract description 4
- 239000000010 aprotic solvent Substances 0.000 claims abstract description 4
- 150000001413 amino acids Chemical class 0.000 claims abstract description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 235000021317 phosphate Nutrition 0.000 claims description 3
- AMDDRMIFTJHJGD-WDSKDSINSA-N (2s)-2-[[(1s)-1-carboxyethyl]amino]pentanoic acid Chemical compound CCC[C@@H](C(O)=O)N[C@@H](C)C(O)=O AMDDRMIFTJHJGD-WDSKDSINSA-N 0.000 claims description 2
- CQYBNXGHMBNGCG-FXQIFTODSA-N (2s,3as,7as)-2,3,3a,4,5,6,7,7a-octahydro-1h-indol-1-ium-2-carboxylate Chemical compound C1CCC[C@@H]2[NH2+][C@H](C(=O)[O-])C[C@@H]21 CQYBNXGHMBNGCG-FXQIFTODSA-N 0.000 claims description 2
- 229940024606 amino acid Drugs 0.000 claims description 2
- 150000001642 boronic acid derivatives Chemical class 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000000539 amino acid group Chemical group 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 239000005541 ACE inhibitor Substances 0.000 abstract description 6
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 abstract description 6
- 238000003786 synthesis reaction Methods 0.000 abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 2
- 230000000707 stereoselective effect Effects 0.000 abstract description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical group OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 abstract 1
- 239000010452 phosphate Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108010061435 Enalapril Proteins 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 3
- 229960002582 perindopril Drugs 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 3
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229960000873 enalapril Drugs 0.000 description 2
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- CEIWXEQZZZHLDM-AMGKYWFPSA-N (2s)-2-[(1-ethoxy-1-oxo-4-phenylbutan-2-yl)amino]propanoic acid Chemical compound CCOC(=O)C(N[C@@H](C)C(O)=O)CCC1=CC=CC=C1 CEIWXEQZZZHLDM-AMGKYWFPSA-N 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- FMVLIEVJRBLHDX-UHFFFAOYSA-N 2,3,3a,4,5,6,7,7a-octahydroindole-1-carboxylic acid Chemical compound C1CCCC2N(C(=O)O)CCC21 FMVLIEVJRBLHDX-UHFFFAOYSA-N 0.000 description 1
- FBAOVPVVMDOHPK-UHFFFAOYSA-N 2-(1h-imidazol-2-ylsulfinyl)-1h-imidazole Chemical compound N=1C=CNC=1S(=O)C1=NC=CN1 FBAOVPVVMDOHPK-UHFFFAOYSA-N 0.000 description 1
- FJPFWMYTFGJMAN-UHFFFAOYSA-N 2-sulfinylimidazole Chemical compound O=S=C1N=CC=N1 FJPFWMYTFGJMAN-UHFFFAOYSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- 229930182821 L-proline Natural products 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 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
- 238000006664 bond formation reaction Methods 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 1
- 229960000309 enalapril maleate Drugs 0.000 description 1
- OYFJQPXVCSSHAI-QFPUQLAESA-N enalapril maleate Chemical compound OC(=O)\C=C/C(O)=O.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 OYFJQPXVCSSHAI-QFPUQLAESA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229960002429 proline Drugs 0.000 description 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000013024 troubleshooting Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Podan je postopek za pripravo spojin z ACE inhibitornim delovanjem s formulo I, kjer imajo R1, R2 in R3 zgoraj navedeni pomen pri katerem karboksilno skupino stereospecifične amino kisline aktiviramo z reagenti iz skupine O-Benzotriazolil heksafluoro fosfatov ali tetrafluoro boratov v aprotičnih topilih in nato aktivirano kislino pretvorimo v peptid z aminom, primernim za sintezo ACE inhibitorjev.ŕ
Description
POSTOPEK ZA PRIPRAVO SPOJIN Z ACEINHIBITORNIM DELOVANJEM
PODROČJE TEHNIKE
Izum spada v področje kemijske sinteze in se nanaša na postopek za pripravo spojin z ACE inhibitomim delovanjem
TEHNIČNI PROBLEM
Pri nekaterih substancah z ACE inhibitomim delovanjem so obstoječi postopki komplicirani v smislu uporabe reagentov in tehnologije. Izum omogoča hitro, selektivno in enostavno tvorbo ACE inhibitorjev.
STANJE TEHNIKE
Do zdaj znani postopki za sintezo ACE inhibitoijev v ključni fazi sinteze uporabljajo nekaj v literaturi znanih načinov za tvorbo peptidne vezi:
NCA (Fosgen, di ali tri fosgen, karbonil diimidazol)
Klortionil imidazol ali tionil diimidazol
Dicikloheksil karbodiimid /1-hidroksi benzotriazol
V EP 1 279 665 je opisan postopek za pripravo perindoprila s tvorbo NCA s pomočjo trifosgena. Reakcija daje dobre rezultate vendar zahteva delo s trifosgenom posebno pazljivost. V USP 4 914 214 je opisana sinteza perindoprila s kondenzacijo (2,S,3aS,7aS)-2-22 karboksiperhidro indola ( z zaščiteno karboksilno skupino) z N-((S)-l-karbetoksibutil)-(S)alaninom s pomočjo dicikloheksil karbodiimida in 1-hidroksi benzotriazola. Postopek daje dobre rezultate vendar je potrebna pazljiva izolacija zaradi stranskega produkta dicikloheksil sečnine, ki jo je težje popolnoma izločiti iz reakcijske zmesi. V SI 94 00 290 je opisana sinteza enalaprila s tvorbo peptidne vezi s tionil imidazolom. Reakcija daje zadovoljive rezultate vendar je potrebna striktna kontrola reakcijskih pogojev in absolutno brezvodni mediji, sicer so izkoridtki vprašljivi in so možne stranske reakcije ( tvorba diketopiperazida ipd).
OPIS REŠITVE PROBLEMA Z IZVEDBENIMI PRIMERI
Predmet izuma je postopek za pripravo ACE inhibitorjev s formulo :
R2O
ch3
ali njihove farmacevtsko sprejemljive adicijske soli
RI je lahko : H, alkil, fenil
R2 je lahko : H, alkil R3 je lahko
-N \
(CH2)n /
/
Z r4oocz n=l?2?3
X,Z~CH2, NH,S R4 - ll,Bz,M,Me,Pr,Bu
M=Li,Na,K,Ca ali
»llCOOBz označen s tem, da karbonilno skupino stereospecifične amino kisline
Ri
H
OH
RI, R2 kot zgoraj aktiviramo z reagenti iz serije substituiranih O-Benzotriazolil heksafluoro fosfatov ali tetrafluoro boratov v aprotičnih topilih in nato aktivirano kislino pretvorimo v peptid s primernim aminom iz serije HR3 pri čemer je R3 :
-N (CH2)n /
Z
R4OOC n=l,2,3
X,Z = CH2, NH.S R4 - H,Bz,M,Me,Pr,Bu
M-UNa,K,Ca ali
'IICOOBz
Nastali produkt nato po izolaciji po potrebi prevedemo v farmacevtsko sprejemljivo sol.
Topila primerna za ta tip reakcije so klorirani ogljikovodiki, ciklični ali aciklični ogljikovodiki, estri org. kislin (n.pr, etil acetat), skratka aprotična topila.
Izvedba reakcije je zelo enostavna in ne zahteva posebnih pogojev. Izredno pomembno je, da poteče izredno hitro v primeijavi z ostalimi metodami sinteze ACE inhibitoijev (v 15 minutah) in zaradi izredne selektivnost praktično brez stranskih produktov. Ključna reakcija tvorbe peptidne vezi poteče tako, da 15-30 minut pri sobni temperaturi v topilu mešamo v steheometričnem razmerju (ali z rahlim prebitkom katerekoli komponente) kislino, amin in reagent iz zgoraj omenjene serije. Nastali reakcijski zmesi dodamo vodo in produkt izoliramo s primernim topilom, v katerem je produkt topen. Po spiranju raztopine z vodo in uparenju topila dobimo surov produkt visoke optične in kemijske čistost v visokem izkoristku (8795%).
Reakcijska shema:
OH (R5)2N—c=N(R5)2 o
PF6 ali BF4
R5= Me,Et ali pirolidino
H
Ra
-7Izum ponazarjamo z naslednjimi primeri, ki opisujejo izum, vendar ga ne omejujejo :
Primer 1
V 20 ml MeCN med mešanjem pri sobni temperaturi dodamo 855 mg Benzilnega estra (2S,3aS,7aS)-2-karboksiperhidro indola, 651 mg N-((S)-l-karbetoksibutil)-(S)-alanina in 1137 mg 0-(Benzotriazal-1-H)-NXN\N'-tetrametiluroniumheksafluorofosfata. Po 30 minutah mešanja dodamo 50 ml nasičene raztopine NaCl in produkt ekstrahiramo z dvakrat po 35 ml etil acetata, Združene ekstrakte speremo s 70 ml vode, ki smo ji dodali 1 ml HCI cone. in nato še s 130 ml vode. Ekstrakt sušimo z Na2SO4 in uparimo pri 40 °C v vakuumu. Dobimo 1210 mg (87,8%) Benzil (2Sf3aS,7aS)-((2-(1-(etoksikarbonil)-(S)-butilamino)4S)-propionil)oktahidroindol-2-karboksilata (benzilni ester perindoprila).
Nastali produkt lahko po znanih metodah pretvorimo v prosto kislino in nato v farmacevtsko primerno sol.
Primer 2
2,79 g (S)-l-(N-(l-(etoksikarbonil)-3-fenilpropil)-L-alanina, 1,15 g L-Prolina v 100 ml MeCN in 5 ml DMF, dodamo 2,9 ml trietilamina in med mešanjem še 3,8 g O-iBenzotnazol-l-ilj-N.N.N^N’tetrametiluroniumheksafluorofosfata in mešamo 30 minut pri sobni temperaturi. Dodamo 300 ml nas. raztopine NaCl in ekstrahiramo z dvakrat po 100 ml etilacetata. Produkt izoliramo na enak način kot v primeru 1. Dobimo 3,55 g enalaprila, ki ga raztopimo v 100 ml etilacetata in mu dodamo raztopino 1,00 g maleinske kisline v 20 ml etilacetata. Po 30 minutah odfiltriramo kristale enalapril maleata in jih posušimo v vakuumu pri 40 °C. Dobimo 4,2g produkta (85,4% )
Claims (4)
- PATENTNI ZAHTEVKI1. Postopek za pripravo spojin z ACE inhibitornim delovanjem s formulo :RaIn njihovih farmacevtsko sprejemljivih soli kjer imajo R1-R3 naslednje pomene :RI je lahko : H, alkil, fenilR2 je lahko : H, alkilR3 je lahko:/Xx-N (CH2)nR4OOC n-1,2,3 = CH2, NH,S R4 = H,Bz,M,Me,Pr,BuM=Li,Na,K,Ca aliΗΗ ilCOOBz označen s tem, da karboksilno skupino amino kisline s formulo aktiviramo z reagenti iz skupine substituiranih O-Benzotriazolil heksafluoro fosfatov ali tetrafluoro boratov v aprotičnih topilih in nato aktivirano kislino pretvorimo v peptid s primernim aminom iz serije HR3 pri Čemer je R3 :/x\-N (CH2)n \ /R4OOC n« 1,2,3X,Z CH2, NH,SR4 - H,BzMMe,Pr,BuM=Li,Na,K,Ca-10ΑΟ aliΗ llCOOBzH in nato dobljene produkte po potrebi pretvorimo v farmacevtsko sprejemljive soli.
- 2. Postopek za pripravo spojin z ACE inhibitomim delovanjem kot v zahtevku št. 1 s tem, daje amino kislinaN-((S)-l-karbetoksibutil)-(S)-alanin.
- 3. Postopek za pripravo spojin z ACE inhibitomim delovanjem kot v zahtevku Št. 1 s tem, daje aminBenzilni ester(2S,3aS,7aS)-2-karboksiperhidro indola.
- 4. Postopek za pripravo spojin z ACE inhibitomim delovanjem kot v zahtevku št. 1 s tem, da je reagent za tvorbo peptidne vezi iz serije substituiranih O-Benzotriazolil heksafluoro fosfatov O-(Benzotriazol-1 -il)-NN,N',N'-tetrametiluroniumheksafluorofosfat.
Priority Applications (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI200300123A SI21507A (sl) | 2003-05-16 | 2003-05-16 | Postopek za pripravo spojin z ace inhibitornim delovanjem |
| US10/556,986 US7671215B2 (en) | 2003-05-16 | 2004-05-07 | Process for the preparation of compounds having an ace inhibitory action |
| PCT/SI2004/000021 WO2004101515A1 (en) | 2003-05-16 | 2004-05-07 | A process for the preparation of compounds having an ace inhibitory action |
| RU2005139158/04A RU2377236C2 (ru) | 2003-05-16 | 2004-05-07 | Способ получения соединений, обладающих апф ингибиторной активностью |
| EP04731808A EP1628956B1 (en) | 2003-05-16 | 2004-05-07 | A process for the preparation of compounds having an ace inhibitory action |
| DE602004030112T DE602004030112D1 (de) | 2003-05-16 | 2004-05-07 | Verfahren zur herstellung von ace hemmern |
| SI200431600T SI1628956T1 (sl) | 2003-05-16 | 2004-05-07 | Postopek za pripravo spojin z ACE inhibitornim delovanjem |
| AT04731808T ATE488498T1 (de) | 2003-05-16 | 2004-05-07 | Verfahren zur herstellung von ace hemmern |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI200300123A SI21507A (sl) | 2003-05-16 | 2003-05-16 | Postopek za pripravo spojin z ace inhibitornim delovanjem |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI21507A true SI21507A (sl) | 2004-12-31 |
Family
ID=33448812
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI200300123A SI21507A (sl) | 2003-05-16 | 2003-05-16 | Postopek za pripravo spojin z ace inhibitornim delovanjem |
| SI200431600T SI1628956T1 (sl) | 2003-05-16 | 2004-05-07 | Postopek za pripravo spojin z ACE inhibitornim delovanjem |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI200431600T SI1628956T1 (sl) | 2003-05-16 | 2004-05-07 | Postopek za pripravo spojin z ACE inhibitornim delovanjem |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US7671215B2 (sl) |
| EP (1) | EP1628956B1 (sl) |
| AT (1) | ATE488498T1 (sl) |
| DE (1) | DE602004030112D1 (sl) |
| RU (1) | RU2377236C2 (sl) |
| SI (2) | SI21507A (sl) |
| WO (1) | WO2004101515A1 (sl) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2468724T3 (en) * | 2006-12-21 | 2016-02-22 | Zealand Pharma As | Synthesis of pyrrolidine compounds |
| US20090076126A1 (en) * | 2007-09-17 | 2009-03-19 | Protia, Llc | Deuterium-enriched enalapril |
| AU2010273259B2 (en) | 2009-07-16 | 2013-03-07 | Abbott Laboratories | Processes for the synthesis of (2S, 3aR, 7aS)-octahydro-1H-indole carboxylic acid as an intermediate for trandolapril |
| AU2013328352A1 (en) * | 2012-10-10 | 2015-05-14 | Piramal Enterprises Limited | An improved process for preparation of Perindopril intermediate |
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|---|---|---|---|---|
| NL4915C (sl) | 1913-08-18 | |||
| FR2620709B1 (fr) * | 1987-09-17 | 1990-09-07 | Adir | Procede de synthese industrielle du perindopril et de ses principaux intermediaires de synthese |
| EP0500989B1 (en) * | 1991-02-27 | 1998-12-09 | Lacer, S.A. | N-(alpha-substituted-pyridinyl) carbonyl dipeptide antihypertensive agents |
| DE4334936C1 (de) * | 1993-10-13 | 1995-06-22 | Karla Dr Lehmann | Arzneimittel zur optimierten Behandlung eines erhöhten Blutdrucks und zur Verhütung von Folgeerkrankungen |
| US5864040A (en) | 1996-01-11 | 1999-01-26 | American Home Products Corporation | Benzimidazole phosphono-amino acids |
| RU2119314C1 (ru) * | 1996-02-05 | 1998-09-27 | Московский научно-исследовательский институт глазных болезней им.Гельмгольца | Способ профилактики и лечения изъязвлений роговицы |
| GB9710612D0 (en) | 1997-05-23 | 1997-07-16 | Glaxo Group Ltd | Synthesis of acridine derivatives |
| FR2771010B1 (fr) * | 1997-11-19 | 2003-08-15 | Adir | Utilisation d'une combinaison d'un inhibiteur de l'enzyme de conversion de l'angiotensine et d'un diuretique pour le traitement des desordres microcirculatoires |
| WO2001072728A2 (en) | 2000-03-31 | 2001-10-04 | Pfizer Products Inc. | Novel piperazine derivatives |
| GB2375762B (en) | 2001-05-21 | 2003-10-01 | Fermenta Biotech Ltd | Stereospecific synthesis of 2-hydroxy-4-phenyl-butyric acid esters |
| WO2002094857A1 (en) * | 2001-05-23 | 2002-11-28 | The Curators Of The University Of Missouri | Inverse solid phase synthesis of peptides |
| AR036187A1 (es) | 2001-07-24 | 2004-08-18 | Adir | Un proceso para la preparacion de perindopril, compuestos analogos y sus sales, compuesto intermediario 2,5-dioxo-oxazolidina y proceso para preparar un intermediario |
| GB0119795D0 (en) | 2001-08-14 | 2001-10-03 | Smithkline Beecham Plc | Novel process |
-
2003
- 2003-05-16 SI SI200300123A patent/SI21507A/sl not_active IP Right Cessation
-
2004
- 2004-05-07 AT AT04731808T patent/ATE488498T1/de not_active IP Right Cessation
- 2004-05-07 EP EP04731808A patent/EP1628956B1/en not_active Expired - Lifetime
- 2004-05-07 DE DE602004030112T patent/DE602004030112D1/de not_active Expired - Lifetime
- 2004-05-07 US US10/556,986 patent/US7671215B2/en not_active Expired - Fee Related
- 2004-05-07 WO PCT/SI2004/000021 patent/WO2004101515A1/en not_active Ceased
- 2004-05-07 RU RU2005139158/04A patent/RU2377236C2/ru not_active IP Right Cessation
- 2004-05-07 SI SI200431600T patent/SI1628956T1/sl unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP1628956A1 (en) | 2006-03-01 |
| US20070072919A1 (en) | 2007-03-29 |
| EP1628956B1 (en) | 2010-11-17 |
| ATE488498T1 (de) | 2010-12-15 |
| WO2004101515A1 (en) | 2004-11-25 |
| DE602004030112D1 (de) | 2010-12-30 |
| RU2005139158A (ru) | 2007-06-27 |
| RU2377236C2 (ru) | 2009-12-27 |
| SI1628956T1 (sl) | 2011-03-31 |
| US7671215B2 (en) | 2010-03-02 |
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| IF | Valid on the event date | ||
| OO00 | Grant of patent |
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Effective date: 20130523 |