Patent ID: 6130315
Filing Date: 2000-10-10
Classification: A61K,C07C,C07D,C07K

Abstract:
An activated electrophilic ketone-bearing peptidase inhibitor of the formula: ##STR61## the hydrates thereof, and the pharmaceutically acceptable salts thereof, whereinR.sub.1 is an amino protecting group selected from Group K, an .alpha.-amino acid or a peptide having up to 4 .alpha.-amino acids sequenced in their P.sub.2 to P.sub.5 position, the terminal amine of said .alpha.-amino acid or peptide optionally bearing a protecting group selected from Group K,R.sub.2 is the side chain of an .alpha.-amino acid,X is X.sub.1 or X.sub.2 whereinX.sub.1 is --CF.sub.3, --CF.sub.2 H, CO.sub.2 R.sub.3 or --CONHR.sub.3, ##STR62## R.sub.3 is hydrogen, C.sub.1-4 straight or branched alkyl, phenyl, benzyl, cyclohexyl or cyclohexylmethyl,R.sub.4 is the side chain of an .alpha.-amino acid,R.sub.5 is an .alpha.-amino acid or a peptide having up to 3 .alpha.-amino acids sequenced in their P.sub.2 ' to P.sub.4 ' positions,Y is --NHR.sub.3 or OR.sub.3 with the proviso that when R.sub.2 is a residue of .alpha.-amino acid of group E and the R.sub.1 moiety bears a member of group D in its P.sub.2 position, then X is other than CF.sub.3,wherein the .alpha.-amino acids are selected from Groups A, B, C, D, E, F, G, and J, and K is a terminal amino protecting group, members of these groups beingGroup A: Lys and ArgB: Glu and AspC: Ser, Thr, Gln, Asn, Cys and HisD: ProE: Ala, ILeu, Ile, Val, n-Val, Met and n-LeuF: Phe, Tyr and TrpG: GlyJ: ##STR63## with .PHI. representing phenyl, K: Acetyl(Ac), Succinyl (Suc), Benzoyl (Bz), Carbobenzoxy (CBz), Tosyl (Ts), Dansyl (DNS), and Methoxysuccinyl (MeOSuc).