Aromatic amino-alcohol derivatives having anti-diabetic and anti-obesity properties, their preparation and their therapeutic uses

A pharmaceutical composition for the treatment or prophylaxis of diabetes, obesity, hyperlipemia, hyperglycemia, complications of diabetes, obesity-related hypertension and osteoporosis, which composition comprises an effective amount of an active compound in admixture with a pharmaceutically acceptable carrier or diluent, wherein the active compound is selected from the group consisting of compounds of formula (I):

• ##STR27## wherein:
• R.sup.0 represents a hydrogen atom, a methyl group or a hydroxymethyl group;
• R.sup.1 represents a substituted alkyl group having from 1 to 12 carbon atoms, which group is substituted by at least one substituent selected from the group consisting of substituents A, defined below;
• R.sup.2 and R.sup.3 are independently selected from the group consisting of:
• hydrogen atoms;
• halogen atoms;
• hydroxy groups;
• alkoxy groups having from 1 to 5 carbon atoms;
• carboxy groups;
• alkoxycarbonyl groups having from 2 to 7 carbon atoms;
• alkyl groups having from 1 to 5 carbon atoms;
• nitro groups;
• haloalkyl groups having from 1 to 4 carbon atoms;
• and substituted alkyl groups which have from 1 to 12 carbon atoms and which are substituted by at least one substituent selected from the group consisting of substituents A, defined below;
• X represents an oxygen or sulfur atom;
• and
• Ar represents a group of formula (II) or (III):
• ##STR28## wherein:
• R.sup.4 represents a hydrogen atom, a halogen atom, a hydroxy group, a hydroxymethyl group, an alkoxy group having from 1 to 5 carbon atoms, an alkyl group having from 1 to 5 carbon atoms, an aliphatic carboxylic acyloxy group having from 1 to 6 carbon atoms, a nitro group, a cyano group, an aralkyloxy group, in which the aralkyl part is as defined below, an aryloxy group in which the aryl part is as defined below, an aryl group as defined below or a haloalkyl group having from 1 to 4 carbon atoms;
• R.sup.5 represents a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group having from 1 to 5 carbon atoms, an alkyl group having from 1 to 5 carbon atoms or a nitro group;
• and
• R.sup.6 represents a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group having from 1 to 5 carbon atoms or an alkyl group having from 1 to 5 carbon atoms;
• said aralkyl part is an alkyl group which has from 1 to 3 carbon atoms and which is substituted by 1 or 2 aryl groups as defined below;
• said aryl groups are carbocyclic aryl groups which have from 6 to 10 ring carbon atoms and which are unsubstituted or are substituted by at least one substituent selected from the group consisting of substituents B, defined below;
• said substituents A are selected from the group consisting of carboxy groups, alkoxycarbonyl groups having from 2 to 7 carbon atoms, aryloxycarbonyl groups in which the aryl part is as defined above, aralkyloxycarbonyl groups in which the aralkyl part is as defined above, hydroxy groups, and carboxylic acyloxy groups having from 1 to 6 carbon atoms;
• and
• said substituents B are selected from the group consisting of halogen atoms, alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 3 carbon atoms, nitro groups, haloalkyl groups having from 1 to 4 carbon atoms and hydroxy groups;
• or a pharmaceutically acceptable salt thereof.

A method for the treatment or prophylaxis of diabetes, obesity, hyperlipemia, hyperglycemia, retinopathy, nephropathy, neuropathy, cataracts, coronary heart diseases;

• arteriosclerosis, obesity-related hypertension and osteoporosis in a mammal, which may be human, which method comprises administering to said mammal an effective amount of an active compound, wherein the active compound is selected from the group consisting of compounds of formula (I):
• ##STR29## wherein:
• R.sup.0 represents a hydrogen atom, a methyl group or a hydroxymethyl group;
• R.sup.1 represents a substituted alkyl group having from 1 to 12 carbon atoms, which group is substituted by at least one substituent selected from the group consisting of substituents A, defined below;
• R.sup.2 and R.sup.3 are independently selected from the group consisting of:
• hydrogen atoms;
• halogen atoms;
• hydroxy groups;
• alkoxy groups having from 1 to 5 carbon atoms;
• carboxy groups;
• alkoxycarbonyl groups having from 2 to 7 carbon atoms;
• alkyl groups having from 1 to 5 carbon atoms;
• nitro groups;
• haloalkyl groups having from 1 to 4 carbon atoms;
• and substituted alkyl groups which have from 1 to 12 carbon atoms and which are substituted by at least one substituent selected from the group consisting of substituents A, defined below;
• X represents an oxygen or sulfur atom;
• and
• Ar represents a group of formula (II) or (III):
• ##STR30## wherein:
• R.sup.4 represents a hydrogen atom, a halogen atom, a hydroxy group, a hydroxymethyl group, an alkoxy group having from 1 to 5 carbon atoms, an alkyl group having from 1 to 5 carbon atoms, an aliphatic carboxylic acyloxy group having from 1 to 6 carbon atoms, a nitro group, a cyano group, an aralkyloxy group, in which the aralkyl part is as defined below, an aryloxy group in which the aryl part is as defined below, an aryl group as defined below or a haloalkyl group having from 1 to 4 carbon atoms;
• R.sup.5 represents a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group having from 1 to 5 carbon atoms, an alkyl group having from 1 to 5 carbon atoms or a nitro group;
• and
• R.sup.6 represents a hydrogen atom, a halogen atom, a hydroxy group, an alkoxy group having from 1 to 5 carbon atoms or an alkyl group having from 1 to 5 carbon atoms;
• said aralkyl part is an alkyl group which has from 1 to 3 carbon atoms and which is substituted by 1 or 2 aryl groups as defined below;
• said aryl groups are carbocyclic aryl groups which have from 6 to 10 ring carbon atoms and which are unsubstituted or are substituted by at least one substituent selected from the group consisting of substituents B, defined below;
• said substituents A re selected from the group consisting of carboxy groups, alkoxycarbonyl groups having from 2 to 7 carbon atoms, aryloxycarbonyl groups in which the aryl part is as defined above, aralkyloxycarbonyl groups in which the aralkyl part is as defined above, hydroxy groups, and carboxylic acyloxy groups having from 1 to 6 carbon atoms;
• and
• said substituents B are selected from the group consisting of halogen atoms, alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 3 carbon atoms, nitro groups, haloalkyl groups having from 1 to 4 carbon atoms and hydroxy groups;
• or a pharmaceutically acceptable salt thereof.