EP0575572A1 - Stabile Salze von (+)-(IS,2R)-2-[[N-(2-Hydroxylamino-2-oxoäthyl)N-methylamino]carbonyl]cyklohexan-1-carbonsäure - Google Patents
Stabile Salze von (+)-(IS,2R)-2-[[N-(2-Hydroxylamino-2-oxoäthyl)N-methylamino]carbonyl]cyklohexan-1-carbonsäureInfo
- Publication number
- EP0575572A1 EP0575572A1 EP92924726A EP92924726A EP0575572A1 EP 0575572 A1 EP0575572 A1 EP 0575572A1 EP 92924726 A EP92924726 A EP 92924726A EP 92924726 A EP92924726 A EP 92924726A EP 0575572 A1 EP0575572 A1 EP 0575572A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- carbonyl
- carboxylic acid
- salts
- oxoethyl
- alkaline
- 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.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/26—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one amino group bound to the carbon skeleton, e.g. lysine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Definitions
- This invention refers to novel salts of
- (+)-(lS,2R)-2-[[N-(2-hydroxylamino-2-oxoethyl)-N-methyl-amino]carbonyl]cyclohexane- 1-carboxylic acid 1, (D.C.I. Idrapril) is a compound disclosed in the European Patent Application No. 89106304.2 as a novel ACE- inhibitory agent and therefore having antihypertensive activity.
- This acid when kept exposed to the air in the normal environmental conditions of humidity and temperature, is subject to autodecomposition processes which give rise to impurities obviously incompatible with regard to a therapeutical use. Such degradation processes are also accelerated by a temperature increase of the acid kept in the above conditions.
- novel salts according to this invention do not undergo to the autodecomposition and degradation processes previously mentioned.
- the salts of the invention are stable compounds in the normal environmental conditions. Further the salts remain unchanged with time either kept as such or included (in a solid state) in a pharmaceutical preparation (tablets, pills, capsules, lyophilized compositions and the like) provided for their therapeutical use.
- a pharmaceutical preparation tablettes, pills, capsules, lyophilized compositions and the like
- the preparation of the compounds of the invention is based on a process characterized in that a compound, selected between
- (+)-(1S,2R)-2-[[N-(2-hydroxyIamino-2-oxoethyl)-N-methylam ⁇ no]carbonyllcyclohexane-1 -carboxylic acid 1, is reacted with a compound selected among hydrates and carbonates or other suitable salts of alkaline and alkaline-earth metals, as defined in the present invention, as well as with organic bases, in an organic solvent or mixtures thereof with water, the reaction taking place, in the case of the starting product 2, contemporaneous hydrogenalysis of the protecting benzyl group with hydrogen at atmospheric pressure, in the presence of a suitable hydrogenation catalyst, the process being completed by isolating the desired salt of the acid.
- Q is said hydroxide, or alkaline salt or calcium salt or an organic base.
- the preferred hydrogenation catalyst is charcoal-supported Pd, but PtO 2 ,Rh/Al 2 O 3 and Ni-Raney can also be used.
- propanol, tetrahydrofuran and dioxane are also suitable besides methanol and ethanol.
- the catalyst was filtered and washed with awater/methanol (1/1) mixture (300 ml) and the filtrate, combined with the washings, concentrated under vacuum at 40°C until all the methanol has been removed.
- the final suspension was cooled for 20 hours at 0-4°C and the precipitate was filtered and washed on the filter with 70 ml precooled water at 0-4°C.
- (+)-(1S,2R)-2-[[N-(2-hydroxylamino-2-oxoethyI)-N-methylamino ⁇ carbonyl]cyclohexane-1 -carboxylic acid 1 were added and the mixture was further vigorously stirred for 60 minutes at 20°C.
- the light suspension thus obtained was filtered (on paper) and the filtrate was concentrated under vacuum at 40°C to 200 mL.
- the precipitated product was filtered and washed on filter with 50 mL of precooled water at 0-4°C.
- Sample preparation Dissolve 20 mg of sample substance in 100 ml H 2 O/CH 3 CN 80/20
- Table 1 shows the results, and in the first column, the data for the acid 1, tested in the same way, are reported.
- the salts of the invention are also, within the suitable dosage ratios, practically comparable either for potency and for the activity lasting time to the acid 1.
- the salts of this invention constitute the active ingredients for preparing pharmaceutical compositions both for oral and parenteral use.
- compositions and preparations are made with the well-known pharmaceutical techniques and employing conventional excipients, carriers and solvents.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (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)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ITMI913448A IT1252708B (it) | 1991-12-23 | 1991-12-23 | Sali stabili dell'acido (+)-(1r,2s)-2((n-(2-idrossilammino-2-ossoetil)-n-metilammino)carbonil)cicloesan-1-carbossilico,ad attivita' ace inibitrice, procedimento per la loro preparazione e composizioni farmaceutiche che li contengono. |
ITMI91344 | 1991-12-23 |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0575572A1 true EP0575572A1 (de) | 1993-12-29 |
Family
ID=11361409
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP92924726A Withdrawn EP0575572A1 (de) | 1991-12-23 | 1992-12-12 | Stabile Salze von (+)-(IS,2R)-2-[[N-(2-Hydroxylamino-2-oxoäthyl)N-methylamino]carbonyl]cyklohexan-1-carbonsäure |
Country Status (26)
Country | Link |
---|---|
EP (1) | EP0575572A1 (de) |
JP (1) | JPH06506002A (de) |
CN (1) | CN1079474A (de) |
AU (1) | AU657591B2 (de) |
BG (1) | BG98050A (de) |
BR (1) | BR9205652A (de) |
CA (1) | CA2104372A1 (de) |
CZ (1) | CZ379692A3 (de) |
EE (1) | EE9400006A (de) |
FI (1) | FI933685A (de) |
HR (1) | HRP921454A2 (de) |
HU (1) | HUT69287A (de) |
IT (1) | IT1252708B (de) |
LV (1) | LV10426B (de) |
MA (1) | MA22749A1 (de) |
MX (1) | MX9207543A (de) |
NZ (1) | NZ245547A (de) |
PL (1) | PL169086B1 (de) |
PT (1) | PT101156A (de) |
RU (1) | RU2079489C1 (de) |
SI (1) | SI9200409A (de) |
SK (1) | SK379692A3 (de) |
TN (1) | TNSN92117A1 (de) |
WO (1) | WO1993013056A1 (de) |
YU (1) | YU110892A (de) |
ZA (1) | ZA9210004B (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2817241A1 (fr) | 2000-11-30 | 2002-05-31 | Cebal | Tube aluminium avec embout secable |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1264860B1 (it) * | 1993-06-21 | 1996-10-17 | Guidotti & C Spa Labor | Derivati di acidi cis- e trans-2(((2-(isdrossiammino)-2-ossoetil)- alchilammino)carbonil)cicloesancarbossilici |
US5639746A (en) * | 1994-12-29 | 1997-06-17 | The Procter & Gamble Company | Hydroxamic acid-containing inhibitors of matrix metalloproteases |
US20100035991A1 (en) * | 2006-09-28 | 2010-02-11 | Mckeown Arlene | Amide base salts of saha and polymorphis thereof |
AU2021263319B2 (en) * | 2020-04-27 | 2022-12-01 | Carter-Hoffmann, Llc | Door movement system for cabinet |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IT1224627B (it) * | 1988-04-12 | 1990-10-04 | Guidotti & C Spa Labor | Ammidi di acidi ciclometilen_1,2_dicarbossilici adattivita' terapeutica, procedimenti per la loro preparazione e composizioni farmaceutiche che le contengono. |
-
1991
- 1991-12-23 IT ITMI913448A patent/IT1252708B/it active IP Right Grant
-
1992
- 1992-12-12 AU AU30871/92A patent/AU657591B2/en not_active Ceased
- 1992-12-12 JP JP5511398A patent/JPH06506002A/ja active Pending
- 1992-12-12 BR BR9205652A patent/BR9205652A/pt not_active Application Discontinuation
- 1992-12-12 WO PCT/EP1992/002903 patent/WO1993013056A1/en not_active Application Discontinuation
- 1992-12-12 EP EP92924726A patent/EP0575572A1/de not_active Withdrawn
- 1992-12-12 RU RU9293052414A patent/RU2079489C1/ru active
- 1992-12-12 HU HU9302389A patent/HUT69287A/hu unknown
- 1992-12-12 CA CA002104372A patent/CA2104372A1/en not_active Abandoned
- 1992-12-21 CZ CS923796A patent/CZ379692A3/cs unknown
- 1992-12-21 NZ NZ245547A patent/NZ245547A/en unknown
- 1992-12-21 SK SK3796-92A patent/SK379692A3/sk unknown
- 1992-12-22 MA MA23040A patent/MA22749A1/fr unknown
- 1992-12-22 SI SI9200409A patent/SI9200409A/sl unknown
- 1992-12-22 HR HR921454A patent/HRP921454A2/hr not_active Application Discontinuation
- 1992-12-23 LV LVP-92-358A patent/LV10426B/lv unknown
- 1992-12-23 CN CN92113839A patent/CN1079474A/zh active Pending
- 1992-12-23 PT PT101156A patent/PT101156A/pt not_active Application Discontinuation
- 1992-12-23 YU YU110892A patent/YU110892A/sh unknown
- 1992-12-23 ZA ZA9210004A patent/ZA9210004B/xx unknown
- 1992-12-23 PL PL92297118A patent/PL169086B1/pl unknown
- 1992-12-23 MX MX9207543A patent/MX9207543A/es unknown
- 1992-12-23 TN TNTNSN92117A patent/TNSN92117A1/fr unknown
-
1993
- 1993-08-18 BG BG98050A patent/BG98050A/bg unknown
- 1993-08-20 FI FI933685A patent/FI933685A/fi not_active Application Discontinuation
-
1994
- 1994-05-23 EE EE9400006A patent/EE9400006A/xx unknown
Non-Patent Citations (1)
Title |
---|
See references of WO9313056A1 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2817241A1 (fr) | 2000-11-30 | 2002-05-31 | Cebal | Tube aluminium avec embout secable |
WO2002044045A1 (fr) | 2000-11-30 | 2002-06-06 | Cebal S.A. | Tube aluminium avec embout secable |
Also Published As
Publication number | Publication date |
---|---|
JPH06506002A (ja) | 1994-07-07 |
ZA9210004B (en) | 1993-12-13 |
AU3087192A (en) | 1993-07-28 |
CN1079474A (zh) | 1993-12-15 |
ITMI913448A1 (it) | 1993-06-23 |
YU110892A (sh) | 1996-01-08 |
HUT69287A (en) | 1995-09-28 |
BR9205652A (pt) | 1994-05-03 |
CA2104372A1 (en) | 1993-06-24 |
MA22749A1 (fr) | 1993-07-01 |
RU2079489C1 (ru) | 1997-05-20 |
SI9200409A (en) | 1993-09-30 |
HU9302389D0 (en) | 1993-11-29 |
TNSN92117A1 (fr) | 1993-06-08 |
BG98050A (bg) | 1994-04-29 |
MX9207543A (es) | 1993-08-01 |
IT1252708B (it) | 1995-06-26 |
PT101156A (pt) | 1994-06-30 |
WO1993013056A1 (en) | 1993-07-08 |
EE9400006A (et) | 1995-12-15 |
ITMI913448A0 (it) | 1991-12-23 |
LV10426A (lv) | 1995-02-20 |
HRP921454A2 (en) | 1995-02-28 |
AU657591B2 (en) | 1995-03-16 |
FI933685A0 (fi) | 1993-08-20 |
CZ379692A3 (en) | 1993-09-15 |
PL297118A1 (en) | 1993-09-06 |
SK379692A3 (en) | 1995-04-12 |
FI933685A (fi) | 1993-08-20 |
LV10426B (en) | 1995-08-20 |
NZ245547A (en) | 1995-12-21 |
PL169086B1 (pl) | 1996-05-31 |
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Legal Events
Date | Code | Title | Description |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
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AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LI LU NL PT SE |
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17P | Request for examination filed |
Effective date: 19940309 |
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17Q | First examination report despatched |
Effective date: 19950516 |
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GRAG | Despatch of communication of intention to grant |
Free format text: ORIGINAL CODE: EPIDOS AGRA |
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STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION HAS BEEN WITHDRAWN |
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18W | Application withdrawn |
Withdrawal date: 19960726 |
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RTI1 | Title (correction) |
Free format text: STABLE SALTS OF (+)-(1S,2R)-2- N-(2-HYDROXYLAMINO-2-OXOETHYL)-N-METHYL-AMINO CARBONYL CYCLOHEXANE-1-CARBOXYLIC ACID, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITION |