Amino acids derivatives, the process for their preparation and their applications to therapy

A method of inhibiting the activity of enkephalinase and angiotensin convertase enzymes which comprises adding thereto an effective amount of an amino acid derivative corresponding to the general formula:

• ##STR58## wherein ##STR59## wherein Z and Y are O and n=1 or 2 R.sub.2 represents a hydrogen atom, a lower alkyl group, a lower hydroxyalkylene group, a phenyl group, a lower phenylalkylene group, a lower hydroxyphenylalkylene group, a lower aminoalkylene group, a lower guanidinoalkylene group, a lower mercaptoalkylene group, a lower alkythio lower alkylene group, a lower imidazolylalkylene group, a lower indolyalkylene group, a lower carbamylalkylene group, a lower carboxylalkylene group or one of the following groups:
• ##STR60## wherein Z', Y' and n have the meanings defined below:
• ______________________________________ Z' Y' n ______________________________________ O O 1 O O 2 O CH.sub.2 1 CH.sub.2 CH.sub.2 1 CH.sub.2 CH.sub.2 2 ______________________________________
• X designates the group responsible for chelating the zinc atom of the enzymes (enkephalinase and ACE) selected from the group consisting of a mercaptomethyl, hydroxamic acid, an N-carboxylalkyl of the formula ##STR61## wherein R.sub.3 represents a benzyl lower alkyl radical or lower alkoxy radical, or phosphorated derivatives of formula ##STR62##

A composition acting as mixed inhibitor of the enkephalinase and ACE enzymes which comprises an effective amount of an amino acid derivative corresponding to the general formula:

• ##STR63## wherein for the formula (Ia) R.sub.1 represents a biphenyl group or one of the following groups, ##STR64## wherein Z, Y and n have the meanings defined below:
• ______________________________________ Z Y n ______________________________________ O O 1 O CH.sub.2 1 CH.sub.2 CH.sub.2 1 O O 2 CH.sub.2 CH.sub.2 2 or ##STR65## ______________________________________
• wherein for the formula (Ib) R.sub.1 has the meaning defined herein above and can also be a phenyl group;
• wherein R'.sub.1 represents a hydrogen atom, a lower alkyl group, a phenyl group, a lower phenyalkylene group;
• R.sub.2 represents a hydrogen atom, a lower alkyl group, a lower hydroxyalkylene group, a phenyl group, a lower phenylalkylene group, a lower hydroxyphenylalkylene group, a lower aminoalkylene group, a lower guanidinoalkylene group, a lower mercaptoalkylene group, a lower alkythio lower alkylene group, a lower imidazolylalkylene group, a lower indolyalkylene group, a lower carbamylalkylene group, a lower carboxylalkylene group or one of the following groups:
• ##STR66## wherein Z', Y' and n meanings defined below:
• ______________________________________ Z' Y' n ______________________________________ O O 1 O O 2 O CH.sub.2 1 CH.sub.2 CH.sub.2 1 CH.sub.2 CH.sub.2 2 ______________________________________
• X designates the group responsible for chelating the zinc atom of the enzymes (enkephalinase and ACE) selected from the group consisting of a mercaptomethyl, hydroxamic acid, an N-carboxylalkyl of the formula ##STR67## wherein R.sub.3 represents a benzyl lower alkyl radical or lower alkoxy radical phosphorated derivatives of formula ##STR68## provided that when in the formula (Ia) X is mercaptomethyl, hydroxamic acid or phosphorated derivatives of the formula given above and R.sub.2 is as defined above, R.sub.1 cannot be a phenyl group substituted by a hydroxyl radical,
• provided that when in the formula (Ia) X is mercaptomethyl and R.sub.2 is a lower alkylthio lower alkylene, R.sub.1 cannot be a phenyl group substituted by a lower alkoxy radical, a phenoxyphenyl group or a biphenyl group,
• provided that when in the formula (Ia) X is a hydroxamic acid group and R.sub.2 is a hydrogen atom, a lower alkyl group and a lower alkylthio lower alkylene group, R.sub.1 cannot be a phenyl group substituted by a lower alkoxy
• provided that when in the formula (Ib) X is a hydroxamic acid group or a phosphorated derivative of formula ##STR69## R.sub.2 represents a hydrogen atom, a lower alkyl group, a lower hydroxyalkylene group, a phenyl group, a lower phenylalkylene group, a lower hydroxyphenylalkylene group, a lower mercaptoalkylene group, a lower alkylthio alkylene group and a lower imidazolylalkylene group, R.sub.1 cannot be a phenyl group or a phenyl substituted by a hydroxy radical.