Preparation of furanone dipeptides as cathepsin S inhibitors.

Abstract

The invention relates to compds. I [R2C is a cycloalkyl ring; R1 is alkyl optionally substituted by halogen and hydroxy; R2 is halo, hydroxy, methoxy, or alkyl optionally substituted by halogen, hydroxy or methoxy; E is CO, SO0-2, NR6SO0-2, NR4CO, O2C; R3 is an optionally substituted carbocyclic or heterocyclic ring; R4 is H or alkyl; R5 is H, OR7, SR7 or together with the gem H is :O or (OR7)2; R6, R7 are H, alkyl, etc.] or their pharmaceutically-acceptable salts which have utility in the inhibition of cathepsin S and are thus useful pharmaceuticals against autoimmune disorders, chronic pain, etc. Thus, dipeptide deriv. II, prepd. by a multistep sequence starting from N-Boc protected (S)-3-(1-methylcyclopentyl)alanine benzyl ester, showed ki = 10.8 nM for inhibition of cathepsin S. [on SciFinder(R)]