Compounds useful as reversible inhibitors of cysteine proteases

1. A compound of formula (Ia) or (Ib):

wherein:

Het is piperidinyl substituted or unsubstituted with one or more R 5 ;

R 2 is hydrogen;

R 3 is a hydrogen, C1–10 alkyl, C2–10alkylene, C3–8 cycloalkyl, arylC1–5alkyl or aryl wherein R 3 is substituted or unsubstituted by one or more R c ;

R c is C1–10 alkyl, C3–8 cycloalkyl or aryl,

R 4 is hydrogen;

R 5 is hydrogen or C1–10 alkyl

wherein R 1 and R 6 in the formulas (Ia) or (Ib) form a heteroring

wherein each heteroring is substituted or unsubstituted by one or more R 7 ;

each R 7 and R 8 are independently:

C1–5 alkyl chain optionally halogenated, and

X is ═O

or the pharmaceutically acceptable acceptable salts, esters, tautomers, individual isomers and mixtures of isomers thereof with the proviso that N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-2-(2-oxo-2H-benzo[e][1,3]oxazin-4-ylamino)-propionamide is excluded.

2. The compound according to claim 1 wherein:

R 3 is hydrogen, C1–5 alkyl, C2–5alkylene, C3–7 cycloalkyl, arylC1–3alkyl or aryl wherein R 3 is substituted or unsubstituted by one or more R c ;

R c is C1–5 alkyl, C3–7 cycloalkyl or aryl,

R 5 is hydrogen or C1–8 alkyl.

3. The compound according to claim 2 wherein

R 3 is hydrogen, C1–5 alkyl, C2–5alkylene, C4–6 cycloalkyl or arylC1–2alkyl wherein R 3 is substituted or unsubstituted by one or more R c ;

R c is C1–4 alkyl, C5–6 cycloalkyl, phenyl or naphthyl,

R 5 is hydrogen, or C1–6 alkyl,

R 7 and R 8 are independently C1–4 alkyl.

4. The compound according to claim 3 wherein:

R 3 is C1–3 alkyl, C2–4alkylene, C5–6 cycloalkyl, benzyl or naphthylmethyl wherein R 3 is substituted or unsubstituted by one or more R c ;

R c is C1–3 alkyl, C5–6 cycloalkyl, phenyl or naphthyl,

R 5 is hydrogen, or C1–5 alkyl, and

R 1 and R 6 of the formula (Ia) or Formula (Ib) form a heteroring

wherein each ring is optionally independently substituted by one or two R 7 .

5. The compound according to claim 4 wherein:

R 3 is C1–3 alkyl, C2–4alkylene, C5–6 cycloalkyl, benzyl or naphthylmethyl wherein R 3 is substituted or unsubstituted by one or more R c ;

R c is methyl, ethyl, n-propyl, i-propyl or C5–6 cycloalkyl,

R 5 is hydrogen, or C1–4 alkyl.

6. The compound according to claim 5 wherein:

Het is piperidin-4-yl or piperidin-3-yl each ring being substituted or unsubstituted with one or more R 5 ;

R 3 is methyl, ethyl, n-propyl, propenyl, butenyl, i-butenyl, cyclohexyl, benzyl or naphthylmethyl wherein R 3 is substituted or unsubstituted by one or more R c ;

R c is methyl, ethyl, n-propyl, i-propyl, cyclohexyl or cyclopentyl,

R 5 is hydrogen, or C1–4 alkyl.

7. The compound according to claim 6 wherein:

R 3 is ethyl, n-propyl; propenyl, butenyl, i-butenyl, benzyl or naphthylmethyl wherein R 3 is substituted or unsubstituted by one or more R c ;

R c is methyl, cyclohexyl or cyclopentyl,

R 5 is methyl, ethyl, n-propyl, n-butyl, t-butyl, i-propyl or i-butyl.

8. A compound selected from:

4-Methyl-2-(2-oxo-2H-benzo[e][1,3]oxazin-4-ylamino)-pentanoic acid (4-cyano-1-methyl-piperidin-4-yl)-amide and

4,4-Dimethyl-2-(2-oxo-2H-benzo[e][1,3]oxazin-4-ylamino)-pentanoic acid (4-cyano-1-propyl-piperidin-4-yl)-amide

or the pharmaceutically acceptable acceptable salts, esters, tautomers, individual isomers and mixtures of isomers thereof.

9. A pharmaceutical composition comprising a pharmaceutically effective amount of a compound according to claim 1 .

10. A method of treating a disease chosen from rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, Guillain-Barre syndrome, psoriasis, scleroderma and; atopic dermatitis said method comprising administering to a patient a pharmaceutically effective amount of a compound according to claim 1 .

11. A method of treating atherosclerosis comprising administering to a patient in need of such treatment a pharmaceutically effective amount of a compound according to claim 1 .

12. A method of treating osteoporosis comprising administering to a patient in need of such treatment a pharmaceutically effective amount of a compound according to claim 1 .