DE2558719B2 - ALPHA CURVED CLAMP ON 4-ANGLE BRACKET ON 2- (2.4-DICHLOROBENZOYLAMINO) -AETHYL ANGLE BRACKET FOR -PHENOXY CURVED BRACKET FOR-ISOBUTTERIC ACID, THEIR METHYL AND AETHYLESTERS, THE ENERGY DETERGENTS AND THEIR PHARMACEUTICALS - Google Patents
ALPHA CURVED CLAMP ON 4-ANGLE BRACKET ON 2- (2.4-DICHLOROBENZOYLAMINO) -AETHYL ANGLE BRACKET FOR -PHENOXY CURVED BRACKET FOR-ISOBUTTERIC ACID, THEIR METHYL AND AETHYLESTERS, THE ENERGY DETERGENTS AND THEIR PHARMACEUTICALSInfo
- Publication number
- DE2558719B2 DE2558719B2 DE19752558719 DE2558719A DE2558719B2 DE 2558719 B2 DE2558719 B2 DE 2558719B2 DE 19752558719 DE19752558719 DE 19752558719 DE 2558719 A DE2558719 A DE 2558719A DE 2558719 B2 DE2558719 B2 DE 2558719B2
- Authority
- DE
- Germany
- Prior art keywords
- bracket
- curved
- phenoxy
- angle bracket
- dichlorobenzoylamino
- 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.)
- Granted
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/12—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by halogen atoms or by nitro or nitroso groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Emergency Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Gegenstand der Patentanmeldung P 21 49 070.0-42 sind Phenoxyalkylcarbonsäurederivate der allgemeinen Formel IThe subject of patent application P 21 49 070.0-42 are phenoxyalkylcarboxylic acid derivatives of the general Formula I.
R RaR Ra
R,R,
in welcher Ri Wasserstoff oder Halogen, Rj Wasserstoff oder eine Melhoxy-Gruppe, Rj und R4 Wasserstoff oder eine Methyl-Gruppe, η die Zahlen 1 bis 3 und Z eine Hydroxy- oder Alkoxy-Gruppe mit bis zu 2 Kohlenstoffatomen bedeuten, sowie deren pharmakologisch verträgliche Salze, ferner Verfahren zur Herstellung derselben sowie Arzneimittel, die diese enthalten.in which Ri is hydrogen or halogen, Rj is hydrogen or a melhoxy group, Rj and R4 is hydrogen or a methyl group, η denotes the numbers 1 to 3 and Z denotes a hydroxyl or alkoxy group with up to 2 carbon atoms, as well as their pharmacological meanings compatible salts, also processes for the production of the same as well as medicaments containing them.
Die Verbindungen sowie ihre pharmakologisch verträglichen Salze zeigten im Tierversuch eine starke Senkung der Serumlipide und des Cholesterinspiegels, ohne daß dabei unerwünschte Nebenwirkungen auftraten. The compounds and their pharmacologically acceptable salts showed a strong effect in animal experiments Lowering of serum lipids and cholesterol levels without any undesirable side effects.
ClCl
In Ausgestaltung des Erfindungsgedankens der Hauptanmeldung wurde nun gefunden, daß auch diejenigen Verbindungen der allgemeinen Formel I eine gute lipidsenkende Wirkung aufweisen, in der sowohl R, als auch R2 Halogen bedeuten; als überraschend besser wirksam als Verbindungen der Hauptanmeldung hat sich die Ä-j4-[2-(2,4-Dichlorbenzoylamino)-äthyl]-phenoxy|-isobuttersäure erwiesen.In an embodiment of the inventive concept of the main application, it has now been found that those compounds of the general formula I also have a good lipid-lowering effect in which both R and R 2 are halogen; A -j4- [2- (2,4-dichlorobenzoylamino) ethyl] phenoxy | isobutyric acid has proven to be surprisingly more effective than compounds of the main application.
Gegenstand der vorliegenden Erfindung ist demnach «-(4-[2-(2,4-DichlorbenzoyIamino)-äthyl]-phenüxy|-isobuttersäureder Formel ΓThe subject of the present invention is therefore «- (4- [2- (2,4-Dichlorobenzoyiamino) -ethyl] -phenoxy | -isobutyric acid Formula Γ
^CO-NH- CH2-^ CO-NH- CH 2 -
ClCl
CH3 CH 3
)—C-COOH
CH1 ) —C-COOH
CH 1
deren Methyl- und Äthylester, deren pharmakologisch verträgliche Salze sowie Arzneimittel, die diese Verbindungen als Wirkstoff enthalten.their methyl and ethyl esters, their pharmacologically acceptable salts and drugs that contain them Contain compounds as an active ingredient.
Die Herstellung der neuen Verbindungen erfolgt, wie in den nachfolgenden Beispielen aufgezeigt, nach den in der Hauptanmciclung beschriebenen Verfahren:The preparation of the new compounds takes place, as shown in the following examples, according to the in The procedure described in the main notice:
i\-|4-['2-(2,4-Dichlorbcnzoylamino)-äthyl]-phenoxyj-isobuttersäurcätliylester i \ - | 4 - ['2- (2,4-Dichlorobenzoylamino) ethyl] phenoxy / isobutyric acid ethyl ester
Zu einer Lösung von 12,5 g (0,05 Mmol) a-[4-(2-Aminoäthyl)-phenoxy]-isobuttersäureälhylestcr in 150 ml absolutem l'yriclin werden unter Rühren bei 5-10"C 10,4 g (0,05 Mol) 2,4-Dichlorbenzoylchlorid getropft. M;in entfernt das Kühlb;id und rührt noch 30 Minuten /ur Vervollständigung der Reaktion bei Zimmertemperatur nach. Dann giel.il man auf Lis, stellt mit kon/.10.4 g ( 0.05 mol) 2,4-dichlorobenzoyl chloride was added dropwise. M; in removed the cooling bath and stirred for a further 30 minutes at room temperature to complete the reaction.
ΙΙΙΠΙΙΜΙΙΙΙΠΙΙΜΙ
. "HI I / ΊιΙίΙ I C ΊιΙΙΙίΊ ^. "HI I / ΊιΙίΙ I C ΊιΙΙΙίΊ ^
AlIiLT Mill. Die ÄiIiltIosiiml' wuscht man icAlIiLT Mill. The ÄiIiltIosiiml 'is washed ic
0,5 η-Salzsäure und Natriumhydrogencarbonatlösung. trocknet und engt ein. Der Rückstand wird aus Isopropanol umkristallisiert. Man erhält 19,5 g (92% d. Th.) Ä-j4-[2-(2,4-Dichlorbenzoylamino)-äthyl]-phcnoxy}-isobuttersäureäthylester mit dem Schmp. 82-83° C.0.5 η-hydrochloric acid and sodium hydrogen carbonate solution. dries and constricts. The residue will be off Isopropanol recrystallized. 19.5 g (92% of theory) of ethyl α-j4- [2- (2,4-dichlorobenzoylamino) ethyl] phenoxy} isobutyric acid are obtained with a melting point of 82-83 ° C.
iX-|4-[2-(2,4-Dichlorbenzoylamino)-älhyl]-phenoxy|-isobuttci"säure iX- | 4- [2- (2,4-dichlorobenzoylamino) ethyl] phenoxy | isobuttic acid
Man erwärmt eine Lösung von 18,8 g (44 niMol) ix(4-[2-(2,4-Dichlorben/ylamino)-äihyl]-phenoxy(-isobuttcrsäureäthylester in einem Gemisch aus 200 ml Methanol und 88 ml I n-Kalilaugc 2 Stunden auf 45"C und dampft im Vakuum zur Trockne ein. Den Rückstand nimmt man in Wasser auf, wuscht zweimal mit Äther und säuert die wäßrige Phase an. Der Niederschlag wird abfiltriert und mit Wasser ausgewaschen. Man erhall 'i;i)ii/; ;i Tj, \ ^ i.i 12 '? λ Djchlorbeu/i)"!;!!!!!!'.!!^ ■ plu'now !■■isohiilti.-rsäiire. Sch η ι p. 110— 111 "C.A solution of 18.8 g (44 mmoles) of ix (4- [2- (2,4-dichlorobenzene / ylamino) ethyl] phenoxy (ethyl isobutyrate in a mixture of 200 ml of methanol and 88 ml of I n- Kalilaugc at 45 ° C. for 2 hours and evaporated to dryness in vacuo. The residue is taken up in water, washed twice with ether and the aqueous phase acidified. The precipitate is filtered off and washed out with water. ii /; i T j \ ^ ii 12 'λ Djchlorbeu / i) ";? !!!!!!'.! !! ^ ■ ■■ plu'now isohiilti.-rsäiire. Sch η ι p. 110-111 "C.
VergleichsversucheComparative experiments
Ciofibrinsäure = 2-(p-Chlorphenoxy)-iso-Ciofibric acid = 2- (p-chlorophenoxy) -iso-
bultersäure
^ = (x-[4-(4-Chlorbenzoylaminoäthyl)-shoulder acid
^ = (x- [4- (4-chlorobenzoylaminoethyl) -
phenoxy]-isobuttersäure
ρ = <x-[4-(2-Methoxy-5-chlorbenzoyiphenoxy] isobutyric acid
ρ = <x- [4- (2-methoxy-5-chlorobenzoyi
aminoäthyl)-phenoxy]-aminoethyl) phenoxy] -
isobuttersäure
BM 13.339 = a-|4-[2-(2,4-Dichlorbenzoyl-isobutyric acid
BM 13.339 = a- | 4- [2- (2,4-dichlorobenzoyl-
amino)-äthyl]-phenoxy)-iso-amino) -ethyl] -phenoxy) -iso-
buttersäurebutyric acid
Die Verbindungen A und B sind Gegenstand des Patents.. .(Patentanmeldung P 21 49 070.0).The compounds A and B are the subject of the patent ... (patent application P 21 49 070.0).
Männliche Ratten von ca. 200 g Gewicht (jeweils 10 Tiere pro Substanz) erhielten über 6 Tage ein Pulverfutter der Firma INTERMAST GMBH, Bockum-Hövel (Hersteller Plange, Soest), dem die zu prüfenden Substanzen in den unten angegebenen Konzentrationen beigemischt waren. Am 7. Tag wurden die Tiere ohne Absetzen des Substanzfutters durch Nackenschlag getötet und ausgeblutet. Im Serum wurden die Triglyceride enzymatisch nach Kreutz und Eggst ei η (Klin. Wschr.4O, 363/1962; 44, 262/1966) in der Modifikation nach Schmidt et al. (Z. Klin. ehem. u.Male rats weighing approx. 200 g (10 animals per substance in each case) received one over a period of 6 days Powder feed from INTERMAST GMBH, Bockum-Hövel (Manufacturer Plange, Soest), to which the substances to be tested in the concentrations given below were mixed in. On the 7th day, the animals were blown in the neck without stopping the substance feed killed and bled to death. In the serum, the triglycerides were enzymatically according to Kreutz and Eggst ei η (Klin. Wschr.4O, 363/1962; 44, 262/1966) in the modification according to Schmidt et al. (Z. Klin. Formerly u.
klin. Biochem. 6, 156/1968) und Cholesterin nach Watson (Klin. chim. Acta 5, 637/1960) colorimetrisch bestimmt. In der nachstehenden Tabelle sind die Ergebnisse wiedergegeben.clin. Biochem. 6, 156/1968) and cholesterol Watson (Klin. Chim. Acta 5, 637/1960) colorimetrically certainly. The table below shows the results.
in %Feed conc.
in %
TriglycerideReduction in%
Triglycerides
säureClofibrin
acid
0,1
0,20.025
0.1
0.2
9
309
9
30th
9
90
9
9
0,050.025
0.05
5150
51
3237
32
Aus dem Obigen ergibt sich eindeutig eine Überlegenheit der neuen Verbindung gegenüber dem bekannten Antihyperlipidaemicum Ciofibrinsäure sowie geeigneten Verbindungen gemäß Patent ... (Patentanmeldung P 21 49 070.0).From the above, the superiority of the new compound over the known one clearly emerges Antihyperlipidaemicum Ciofibric acid and suitable compounds according to patent ... (patent application P 21 49 070.0).
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752558719 DE2558719B2 (en) | 1975-12-24 | 1975-12-24 | ALPHA CURVED CLAMP ON 4-ANGLE BRACKET ON 2- (2.4-DICHLOROBENZOYLAMINO) -AETHYL ANGLE BRACKET FOR -PHENOXY CURVED BRACKET FOR-ISOBUTTERIC ACID, THEIR METHYL AND AETHYLESTERS, THE ENERGY DETERGENTS AND THEIR PHARMACEUTICALS |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752558719 DE2558719B2 (en) | 1975-12-24 | 1975-12-24 | ALPHA CURVED CLAMP ON 4-ANGLE BRACKET ON 2- (2.4-DICHLOROBENZOYLAMINO) -AETHYL ANGLE BRACKET FOR -PHENOXY CURVED BRACKET FOR-ISOBUTTERIC ACID, THEIR METHYL AND AETHYLESTERS, THE ENERGY DETERGENTS AND THEIR PHARMACEUTICALS |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| DE2558719A1 DE2558719A1 (en) | 1977-06-30 |
| DE2558719B2 true DE2558719B2 (en) | 1977-12-01 |
| DE2558719C3 DE2558719C3 (en) | 1978-08-24 |
Family
ID=5965657
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752558719 Granted DE2558719B2 (en) | 1975-12-24 | 1975-12-24 | ALPHA CURVED CLAMP ON 4-ANGLE BRACKET ON 2- (2.4-DICHLOROBENZOYLAMINO) -AETHYL ANGLE BRACKET FOR -PHENOXY CURVED BRACKET FOR-ISOBUTTERIC ACID, THEIR METHYL AND AETHYLESTERS, THE ENERGY DETERGENTS AND THEIR PHARMACEUTICALS |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE2558719B2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2898892A1 (en) * | 2006-03-24 | 2007-09-28 | Genfit Sa | New poly-substituted N-(phenethyl)benzamide derivatives are peroxisome proliferator activated receptor activators useful to treat e.g. type-2 diabetes, insulin-resistance, metabolic disorders, atherosclerosis and cardiovascular diseases |
-
1975
- 1975-12-24 DE DE19752558719 patent/DE2558719B2/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| DE2558719C3 (en) | 1978-08-24 |
| DE2558719A1 (en) | 1977-06-30 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C3 | Grant after two publication steps (3rd publication) |