Inhibitors of DP-mediated processes, compositions and therapeutic methods thereof

An inhibitor of a DP-IV mediated process of the following formula:

• ##STR96## where n=1 or 2;
• m=0, 1, or 2;
• X=CH.sub.2, O, S, SO, SO.sub.2, NH or NR.sub.1, wherein R.sub.1 is C.sub.1 -C.sub.6 alkyl;
• Y=N, CH, or .dbd.C, provided that when Y is .dbd.C, then the carbonyl group of A is replaced by CH.dbd. or CF.dbd.;
• R=H, CN, CHO, B(OH).sub.2, C.tbd.C--R.sub.7 or CH.dbd.N--R.sub.8,
• wherein R.sub.7 =H, F, C.sub.1 -C.sub.6 alkyl, CN, NO.sub.2, OR.sub.9, CO.sub.2 R.sub.9, or COR.sub.9,
• wherein R.sub.9 =C.sub.1 -C.sub.6 alkyl;
• and wherein R.sub.8 =Ph, OH, OR.sub.9, OCOR.sub.9 or OBn,
• A is selected from the group consisting of T1, T2 and T3, wherein T1 is a .beta.-amino-acyl group of the formula ##STR97## wherein p is an integer of 1-6, and wherein the ring present in T1 optionally contains one or more heteroatoms, and wherein the ring present in T1 optionally has one or two sites of unsaturation and wherein the carbonyl group of T1 is optionally replaced with CH.dbd. or CF.dbd.;
• T2 is an .alpha.-amino acyl group bearing a cycloaliphatic side chain, wherein the ring present in T2 optionally contains one or more heteroatoms, and wherein the ring present in T2 optionally has one or two sites of unsaturation, and wherein the carbonyl group of T2 is optionally replaced with CH.dbd. or CF.dbd.;
• T3 is an L-.alpha.-amino acid bearing a lipophilic side chain, wherein the carbonyl group of T3 is optionally replaced with CH.dbd. or CF.dbd.;
• with the provisos that,
• (a) A is T1 only if R is H, --CHO or --B(OH)2;
• (b) A is T2 only if R is H;
• and
• (c) A is T3 only if R is CN, C.tbd.C--R.sub.7, or CH.dbd.N--R.sub.8, the ring optionally contains one or two sites of unsaturation and/or heteroatoms and wherein when A-Y comprises an amide moiety, the amide moiety can be replaced by an amide bioisostere.