Hypoglycaemically and hypolipidaemically active derivatives of phenylacetic acid

• US 4,207,341 A
• Filed: 07/01/1976
• Issued: 06/10/1980
• Est. Priority Date: 07/19/1975
• Status: Expired due to Term

• Current Assignee: Boehringer Mannheim Corporation
• Original Assignee: Boehringer Mannheim Corporation
• Inventors: Witte, Ernst-Christian, Hubner, Manfred, Hitzel, Volker, Heerdt, Ruth, Kuhnle, Hans, Weyer, Rudi
• Primary Examiner(s): Evans, Joseph E.
• Assistant Examiner(s): Breitenstein, G. T.
• Application Number:
  US05/701,717
• Time in Patent Office: 1,440 Days
• Field of Search: 260/471 R, 560/37, 560/47, 560/48, 560/42, 560/45, 562/442, 562/455, 562/457, 562/433, 562/456, 424/309, 424/319
• US Class Current: 514/563
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: C07C 279/26 X and Y being nitrogen atoms, i.e. biguanides
• CPC Class Codes: C07D 209/42 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 213/82 in position 3
• CPC Class Codes: C07D 215/48 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 307/79 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
• CPC Class Codes: C07D 311/22 with oxygen or sulfur atoms directly attached in position 4
• CPC Class Codes: C07D 333/38 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

Phenylacetic acid derivatives of the formula ##STR1## wherein A is an aryl radical optionally substituted by halogen, trifluoromethyl, alkyl, alkoxy, alkenyloxy, alkoxyalkoxy, alkyl-substituted amino or aryloxy, or a heterocyclic ring system optionally substituted by halogen, alkyl or alkoxy,

Y is a valency bond or an optionally branched alkylene radical containing up to 3 carbon atoms, and

R₁ and R₂ each independently is hydrogen or a lower alkyl radical,

or a physiologically compatible salt or ester thereof, exhibit marked hypoglycaemic and hypolipidaemic activity.

Claims

1. A phenylacetic acid derivative of the formula ##STR18## wherein A is an aryl radical substituted by halogen, trifluoromethyl, alkyl, alkoxy, alkenyloxy, alkoxyalkoxy, alkyl-substituted amino or aryloxy,

Y is a valency bond or an optionally branched alkylene radical containing up to 3 carbon atoms, and

R₁ and R₂ each independently is hydrogen or a lower alkyl radical,

or a physiologically compatible salt or ester thereof.

2. A compound according to claim 1, wherein Y is an optionally branched alkylene radical containing up to three carbon atoms.

3. A compound according to claim 2 wherein A is a 2-alkoxy-5-halophenyl radical.

4. A compound according to claim 1 wherein such compound is 4-[2-(5-chloro-2-methoxybenzamido)-ethyl]-phenylacetic acid of the formula ##STR19## or a physiologically compatible salt or ester thereof.

5. A compound according to claim 1 wherein such compound is 4-[2-(5-bromo-2-methoxybenzamido)-ethyl]-phenylacetic acid of the formula ##STR20## or a physiologically compatible salt or ester thereof.

6. A compound according to claim 1 wherein such compound is 2-{4-[2-(5-chloro-2-pentyloxybenzamido)-ethyl]-phenyl}-butyric acid of the formula ##STR21## or a physiologically compatible salt or ester thereof.

9. A hypoglycaemically or hypolipidaemically active composition of matter comprising a hypoglycaemically or hypolipidaemically effective amount of a compound according to claim 1 or a physiologically compatible salt or ester thereof in admixture with a physiologically acceptable diluent.

10. A method of reducing the sugar or lipid level in the blood which comprises administering to a patient a hypoglycaemically or hypolipidaemically effective amount of a compound according to claim 1 or a phsiologically compatible salt or ester thereof.

11. The method according to claim 10, wherein said compound is

4-[2-(5-chloro-2-methoxybenzamido)-ethyl]-phenylacetic acid,

4-[2-(5-bromo-2-methoxybenzamido)-ethyl]-phenylacetic acid,

2-{4-[2-(5-chloro-2-pentyloxybenzamido)-ethyl]-phenyl}-butyric acid,

or a physiologically compatible salt or ester thereof.

7. A phenylacetic acid derivative of the formula ##STR22## wherein A is an aryl radical optionally substituted by halogen, trifluoromethyl, alkyl, alkoxy, alkenyloxy, alkoxyalkoxy, alkyl-substituted amino or aryloxy,

Y is an alkylene radical containing up to 3 carbon atoms,

R₁ and R₂ each independently is hydrogen or a lower alkyl radical,

or a physiologically compatible salt or ester thereof.

8. A compound according to claim 7,

wherein

A is an aryl radical containing 6 to 10 carbon atoms optionally substituted by halogen;

trifluoromethyl;

or alkyl, alkoxy, alkenyloxy, alkoxyalkoxy, alkyl-substituted amino each with up to 4 carbon atoms or aryloxy containing 6 to 10 carbon atoms; and

R₁ and R₂ each independently is a hydrogen atom or an alkyl radical with up to 5 carbon atoms.