Carboxyalkyl dipeptide derivatives, process for preparing them and pharmaceutical composition containing them

Claim 1

A process for preparing a compound of the formula wherein R and R 6 are the same or different and are hydroxy, lower alkoxy, lower alkenoxy, diloweralkylamino lower alkoxy, acylamino lower alkoxy, acyloxy lower alkoxy, aryloxy, arloweralkyloxy substituted aryloxy or substituted arloweralkoxy wherein the substituent is methyl, halo, or methoxy, amino, loweralkylamino diloweralkylamino, arloweralkylamino or hydroxyamino; R is hydrogen, alkyl of from 1 to 20 carbon atoms, including branched, cyclic and unsaturated alkyl groups; substituted lower alkyl wherein the substituent is halo hydroxy lower alkoxy aryloxy amino loweralkylamino diloweralkylamino acylamino arylamino guanidino imidazolyl, indolyl, mercapto,' loweralkylthio arylthio carboxy carboxamido carbolower alkoxy phenyl substituted phenyl wherein the substituent is lower alkyl lower alkoxy or halo; arloweralkyl or heteroarloweralkyl, arloweralkenyl or heteroarloweralkenyl, substituted arloweralkyl, substituted heteroarloweralkyl, substituted arloweralkenyl or substituted heteroarloweralkenyl, wherein the substituent is halo or dihalo lower alkyl hydroxy lower alkoxy amino aminomethyl acylamino diloweralkylamino loweralkylamino carboxyl halo loweralkyl cyano or arloweralkyl or heteroarloweralkyl substituted on the alkyl portion by amino or acylamino; R 2 and R 7 are hydrogen or lower alkyl; R 3 is hydrogen lower alkyl phenyl lower alkyl aminomethyl phenyl lower alkyl hydroxy phenyl lower alkyl hydroxy lower alkyl acetylamino lower alkyl acylamino lower alkyl amino lower alkyl dimethylamino lower alkyl halo lower alkyl guanidino lower alkyl imidazolyl lower alkyl indolyl lower alkyl mercapto lower alkyl and loweralkylthio lower alkyl; R 4 is hydrogen or lower alkyl; R 5 is hydrogen lower alkyl phenyl phenyl lower alkyl hydroxy phenyl lower alkyl hydroxy lower alkyl amino lower alkyl guanidino lower alkyl imidazolyl lower alkyl indolyl lower alkyl mercapto lower alkyl or loweralkyl thio lower alkyl; R 4 and R 5 may be connected together to form an alkylene bridge of from 2 to 4 carbon atoms, an alkylene bridge of from 2 to 3 carbon atoms and one sulphur atom, an alkylene bridge of from 3 to 4 carbon atoms containing a double bond or an alkylene bridge as above, substituted with hydroxy lower alkoxy or lower alkyl and the pharmaceutically acceptable salts thereof which comprises reacting a ketone of the formula wherein R 1 may include suitable protection of any reactive groups with a dipeptide or protected dipeptide of the formula wherein R 3 and R 5 may include suitable protection of any reactive groups in the presence of a reducing agent, followed by removal of the protecting groups if necessary to yield the desired product, and, if desired, preparing a salt thereof by conventional means and, if desired, isolating the biologically more active isomer by chromatography or fractional crystallization.