WO1996033984A1 - Anhydrides de n-sulfoxy, procede de preparation et utilisation pour preparer des substances bioactives possedant un effet inhibiteur de ace - Google Patents
Anhydrides de n-sulfoxy, procede de preparation et utilisation pour preparer des substances bioactives possedant un effet inhibiteur de ace Download PDFInfo
- Publication number
- WO1996033984A1 WO1996033984A1 PCT/SI1996/000009 SI9600009W WO9633984A1 WO 1996033984 A1 WO1996033984 A1 WO 1996033984A1 SI 9600009 W SI9600009 W SI 9600009W WO 9633984 A1 WO9633984 A1 WO 9633984A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- preparation
- compound
- sulfoxy
- anhydrides
- Prior art date
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D291/00—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms
- C07D291/02—Heterocyclic compounds containing rings having nitrogen, oxygen and sulfur atoms as the only ring hetero atoms not condensed with other rings
- C07D291/04—Five-membered rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Definitions
- N-sulfoxy anhydrides a process for the preparation thereof and its use for the preparation of bioactive substances having ACE inhibitory action
- the second type uses e.g. N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-N- carboxy-anhydride (NCA; see the formula (II) below) as reactant.
- NCA N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-N- carboxy-anhydride
- EP 0215335 A2 the reaction of N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine of the formula (I)
- R 1 represents PhCFH 2 -CH 2 - or CH 3 CH 2 CH 2 - and R 2 represents methyl or R 3 -NH-(CH 2 ) 3 -CH 2 ,-, R 3 being an amino protecting group, preferably CF 3 CO-.
- the second object of the invention is a process for the preparation of novel N-sulfoxy anhydrides of the formula (III), characterized in that a compound of the formula (IV)
- R 1 in R 2 have the above meanings
- R 4 represents the rest of imidazole, of alkyl imidazole, of benzimidazole, of tetrazole and of similar other heterocyclic compounds.
- the reaction between the compound of the formula (IV) and the compound ot the general formula (V) is carried out in dry organic solvents (humidity ⁇ 0.04% ). preferably in chlorinated organic solvents such as methylene chloride, or non- chlorinated organic solvents such as ethyl acetate, dimethyl carbonate, diethyl carbonate, acetonitrile etc.
- the formed hydrochloride of a heterocyclic compound e.g. imidazole HCl . methyl- imidazole HCl , benzimidazole HCl , tetrazole HCl etc., is filtered off or sucked ott. Organic bases may be regenerated and recycled.
- a heterocyclic compound e.g. imidazole HCl . methyl- imidazole HCl , benzimidazole HCl , tetrazole HCl etc.
- the third object of the invention is a process for the preparation of corresponding ACE inhibitors, wherein NSA (III) is reacted with corresponding derivatives ot amino acids defined below. More particularly, the object of the invention is a process for the preparation of ACE inhibitors of the formula
- R 1 and R 2 are defined as above and R has the following meanings
- inorganic salts e.g. potassium or sodium salts are used.
- organic salts preferably salts of DBU (1.8-diazabicyclo[5.4.0]undec-7-ene).
- DBN (1,5-diazabicyclo[4.3.0]non-5-ene).
- TEA triethylamine
- tetramethylguanidine imidazole. methylimidazole etc. are used.
- octahydro-1H-indole-2-carboxylic acid a pure isomer is used such as 2S,3aS,7aS or 2S,3aR,7aS, SSS or SRS trandolapril is obtained (see J. Med. Chem. 1987, 30, 992-998).
- Synthetised ACE inhibitors are recrystallized from acetonitrile or are purified by reprecipitation in ethyl acetate thus achieving high yields at purification (about 94 %).
- the mother liquor contained the novel compound N-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-N- sulfoxy- anhydride or NSA, which was analyzed.
- NSA is oily liquid, unstable in humidity and air. and has a molecular weight 325 determined by iodometric titration on the basis of the following Scheme:
- NSA thus prepared may be used as starting material for the synthesis of ACE inhibitors.
- Trimethylchlorosilane (5.7 ml: 0.045 mole) was added to a mixture of L-proline (2.47 g; 0.0215 mole), anhydrous methylene chloride (90 ml) and triethylamine (2.5 ml: 0.018 mole) and the mixture was stirred for 2 hours.
- Thionylchloride (0.73 ml; 0.01 mole) was added to dry methylene chloride mixture (25 ml: H 2 O ⁇ ⁇ 0.04 % ) and the mixture was cooled to AC. Then imidazole (2.72 g: 0.04 mole) was added. The mixture was stirred for 65 minutes at a temperature between -5°C and room temperature 20°C.
- opalescent solution A (the preparation thereof is disclosed below) of siiylated (2S.3aS.7aS)- octahydro- 1 H-indole-2-carboxylic acid was added to the filtrate and an opalescent yellow solution was obtained. This solution was stirred for 1 to 6 hours at room temperature (21°C). Then the solution of H 2 O (10 ml) and NaCl (3 g) was added and 35% HCl was added to achieve pH 0.8. It was decanted and the organic phase was washed with water (5 ml). A solution of H 2 O (10 ml) and NaCl (3 g) was added to the organic phase and 33% NaOH was added to achieve pH 4.33.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU52944/96A AU5294496A (en) | 1995-04-24 | 1996-04-22 | N-sulfoxy anhydrides, a process for the preparation thereof and its use for the preparation of bioactive substances havi ng ace inhibitory action |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SI9500140A SI9500140A (en) | 1995-04-24 | 1995-04-24 | Novel n-sulfoxy anhydrides, process for the preparation thereof and its use for the preparation of bioactive substances having ace inhibitory action |
SIP-9500140 | 1995-04-24 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1996033984A1 true WO1996033984A1 (fr) | 1996-10-31 |
Family
ID=20431608
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SI1996/000009 WO1996033984A1 (fr) | 1995-04-24 | 1996-04-22 | Anhydrides de n-sulfoxy, procede de preparation et utilisation pour preparer des substances bioactives possedant un effet inhibiteur de ace |
Country Status (4)
Country | Link |
---|---|
AU (1) | AU5294496A (fr) |
CA (1) | CA2203435A1 (fr) |
SI (1) | SI9500140A (fr) |
WO (1) | WO1996033984A1 (fr) |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1367061A1 (fr) * | 2003-06-30 | 2003-12-03 | Les Laboratoires Servier | Nouveau procédé de synthèse du perindopril et de ses sels pharmaceutiquement acceptables |
WO2004076417A1 (fr) * | 2003-02-27 | 2004-09-10 | Hetero Drugs Limited | Nouvelles formes cristallines de trandolapril |
US7291745B2 (en) | 2005-03-21 | 2007-11-06 | Glenmark Pharmaceuticals Limited | Process for the preparation of perindopril |
US7521566B2 (en) | 2003-02-28 | 2009-04-21 | Les Laboratoires Servier | Process for preparation of perindopril and salts thereof |
US7973173B2 (en) | 2005-07-05 | 2011-07-05 | Cipla Limited | Process for the synthesis of an ACE inhibitor |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SI21703A (en) | 2004-01-14 | 2005-08-31 | Lek Farmacevtska Druzba Dd | Inclusion complexes of perindopril, procedure of their preparation, pharmaceutical compositions containing these complexes and their application in treatment of hypertensia |
SI21881A (sl) | 2004-10-15 | 2006-04-30 | Diagen, Smartno Pri Ljubljani, D.O.O. | Nove kristalne oblike perindopril erbumin hidratov, postopek za njihovo pripravo in farmacevtske oblike, ki vsebujejo te spojine |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0058567A1 (fr) * | 1981-02-17 | 1982-08-25 | Warner-Lambert Company | Dérivés acyliques substitués des acides octahydro-1H-isoindole-1-carboxyliques et de ses esters |
EP0088341A1 (fr) * | 1980-10-06 | 1983-09-14 | Warner-Lambert Company | Dérivés acylés de l'acide octahydro-1H-indole-2-carboxylique |
EP0215335A2 (fr) * | 1985-08-27 | 1987-03-25 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Procédé de préparation de N-[1(S)-éthoxycarbonyl-3-phénylpropyl]-L-alanyl-L-proline |
-
1995
- 1995-04-24 SI SI9500140A patent/SI9500140A/sl not_active IP Right Cessation
-
1996
- 1996-04-22 WO PCT/SI1996/000009 patent/WO1996033984A1/fr active Application Filing
- 1996-04-22 CA CA002203435A patent/CA2203435A1/fr not_active Abandoned
- 1996-04-22 AU AU52944/96A patent/AU5294496A/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0088341A1 (fr) * | 1980-10-06 | 1983-09-14 | Warner-Lambert Company | Dérivés acylés de l'acide octahydro-1H-indole-2-carboxylique |
EP0058567A1 (fr) * | 1981-02-17 | 1982-08-25 | Warner-Lambert Company | Dérivés acyliques substitués des acides octahydro-1H-isoindole-1-carboxyliques et de ses esters |
EP0215335A2 (fr) * | 1985-08-27 | 1987-03-25 | Kanegafuchi Kagaku Kogyo Kabushiki Kaisha | Procédé de préparation de N-[1(S)-éthoxycarbonyl-3-phénylpropyl]-L-alanyl-L-proline |
Non-Patent Citations (2)
Title |
---|
CHEMICAL ABSTRACTS, vol. 114, no. 9, 4 March 1991, Columbus, Ohio, US; abstract no. 81985x, LAVAYSSIERE ET AL: "Oxazoliones and dioxolones containing germanium (IV), germanium (II), phosphorus (III), sulfur." page 755; column 1; XP002008602 * |
PHOSPHORUS, SULFUR SILICON RELAT. ELEM., vol. 53, no. 1-4, 1990, pages 411 - 422 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004076417A1 (fr) * | 2003-02-27 | 2004-09-10 | Hetero Drugs Limited | Nouvelles formes cristallines de trandolapril |
US7521566B2 (en) | 2003-02-28 | 2009-04-21 | Les Laboratoires Servier | Process for preparation of perindopril and salts thereof |
EP1367061A1 (fr) * | 2003-06-30 | 2003-12-03 | Les Laboratoires Servier | Nouveau procédé de synthèse du perindopril et de ses sels pharmaceutiquement acceptables |
WO2005003153A1 (fr) * | 2003-06-30 | 2005-01-13 | Les Laboratoires Servier | Nouveau procede de synthese du perindopril et de ses sels pharmaceutiquement acceptables |
US7179833B2 (en) | 2003-06-30 | 2007-02-20 | Les Laboratoires Servier | Method of synthesising perindopril and the pharmaceutically acceptable salts thereof |
EA008836B1 (ru) * | 2003-06-30 | 2007-08-31 | Ле Лаборатуар Сервье | Новый способ синтеза периндоприла и его фармацевтически приемлемых солей |
AU2004253721B2 (en) * | 2003-06-30 | 2007-12-20 | Les Laboratoires Servier | Novel method of synthesising perindopril and the pharmaceutically-acceptable salts thereof |
US7291745B2 (en) | 2005-03-21 | 2007-11-06 | Glenmark Pharmaceuticals Limited | Process for the preparation of perindopril |
US7973173B2 (en) | 2005-07-05 | 2011-07-05 | Cipla Limited | Process for the synthesis of an ACE inhibitor |
Also Published As
Publication number | Publication date |
---|---|
SI9500140A (en) | 1996-10-31 |
AU5294496A (en) | 1996-11-18 |
CA2203435A1 (fr) | 1996-10-31 |
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