Substituted dipeptides as inhibitors of enkephalinases

A compound having 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
• and the racemates, enantiomers and diastereoisomers thereof and the pharmaceutically acceptable salts thereof, wherein:
• R.sub.1 is alkyl having from 1 to 6 carbon atoms, adamantylmethyl, cycloalkylmethyl having from 4 to 8 carbon atoms or A--X.sub.m --C.sub.n H.sub.2n -- {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- or 3-furanyl, 2- or 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- or 2-naphthyl, 2- or 3-furanyl or 2- or 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 each is independently selected from hydroxy, alkoxy having from 1 to 8 carbon atoms, B--X.sub.m --C.sub.n H.sub.2n --O-- {wherein B is phenyl (which may be substituted with the group Y as defined herein) or 1- and 2- naphthyl;
• and X, m, and n are as defined herein provided that, when n=0, m is zero}, --OCH.sub.2 OCO-alkyl having from 3 to 8 carbon atoms, --OCH.sub.2 CO--phenyl {the 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, cycloalkylmethyl having from 4 to 8 carbon atoms, 2- or 3-thienylmethyl, 2- or 3-furanylmethyl, 1- or 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 selected from 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};
• and 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 as defined herein}, or --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};
• R.sub.5 is hydrogen or alkyl having from 1 to 6 carbon atoms;
• and
• p is 1 or 2.