Substituted dipeptides as inhibitors of enkephalinases

A method for treating depression or schizophrenia in a mammal which method comprises administering an antidepressant or antipsychotic effective amount of a compound having the structural formula I

• R.sub.1 C*H(COR.sub.2)--NH--C*HR.sub.3 --CONH(CH.sub.2).sub.p --C*(R.sub.4 R.sub.5)--COR.sub.6 I
• or a racemate, enantiomer and diasterioisomer thereof or a pharmaceutically acceptable salt thereof to said mammal wherein:
• R.sub.1 is alkyl having from 1 to 6 carbon atoms, adamantylmethyl, cycloakylmethyl having from 4 to 8 carbon atoms or A-X.sub.m -C.sub.n H.sub.2 n- wherein X is oxygen or sulfur, A is phenyl which may be substituted with the group, Y, wherein Y is halogen, hydroxy, trifluoromethyl, alkoxy having from 1 to 6 carbon atoms, alkyl having from 1 to 6 carbon atoms, 2- and 3-furanyl, 2- and 3-thienyl, or phenyl {which may be substituted with halogen, hydroxy, trifluoromethyl, alkoxy having from 1 to 6 carbon atoms or alkyl having from 1 to 6 carbon atoms} benzyl {the phenyl ring of which may be substituted with the group, Y, as defined herein}, 1- and 2-naphthyl, 2- and 3-furanyl or 2- and 3-thienyl;
• m is 0 or 1 and n is 0, 1, 2, 3, or 4;
• R.sub.2 and R.sub.6 may be the same or different and are hydroxy, alkoxy having from 1 to 8 carbon atoms, B-X.sub.m -C.sub.n H.sub.2 n-O- wherein B is phenyl {which may be substituted with the group, Y, as defined herein} or 1- and 2-naphthyl, X, m, and n are as defined herein provided that when n=0, m=0, -OCH.sub.2 OCO-alkyl having from 3 to 8 carbon atoms, -OCH.sub.2 CO-phenyl {phenyl ring of which may be substituted with the group, Y, as defined herein}, 1-glyceryl, ##STR8## wherein R.sub.7 is hydrogen, alkyl having from 1 to 6 carbon atoms, or phenyl which may be substituted with the group, Y, as defined herein, and R.sub.8 is hydrogen or alkyl having from 1 to 6 carbon atoms;
• R.sub.2 may also be --NR.sub.7 R.sub.8 wherein R.sub.7 and R.sub.8 are as defined herein;
• R.sub.3 is alkyl having from 1 to 6 carbon atoms, cyclo-alkylmethyl having from 4 to 8 carbon atoms, 2- and 3-thienylmethyl, 2- and 3-furanylmethyl, 1- and 2-naphthylmethyl, or benzyl the phenyl ring of which may be substituted with the group, Y, as defined herein;
• R.sub.4 is D--C.sub.n H.sub.2n --O.sub.m -- wherein D is hydrogen, alkyl having from 1 to 4 carbon atoms or phenyl which may be substituted with the group, Z, wherein Z is halogen, hydroxy, trifluoromethyl, alkoxy having from 1 to 6 carbon atoms, or alkyl having from 1 to 6 carbon atoms;
• m and n are as defined herein;
• R.sup.4 may also be --NR.sub.5 COR.sub.7 {wherein R.sub.5 and R.sub.7 are defined herein}, and --NR.sub.5 CO.sub.2 R.sub.9 {wherein R.sub.5 is defined herein and R.sub.9 is alkyl having from 1 to 6 carbon atoms or phenyl which may be substituted with the group Y, as defined herein} provided that p is 1 or 2;
• R.sub.5 is hydrogen or alkyl having from 1 to 6 carbon atoms;
• and
• p is 1 or 2.