Pleuromutilin derivatives containing a hydroxyamino- or acyloxyaminocycloalkyl group

1. A compound of general formula I

wherein

R is hydrogen and R 1 is hydroxy or acyloxy, or

R is acyl and R 1 is hydroxy or acyloxy,

X is sulphur, oxygen or NR 10 , wherein R 10 is hydrogen or (C 1-4 )alkyl;

Y is sulphur or oxygen;

R 2 is hydrogen or one or more substituents;

R 4 is hydrogen or (C 1-4 )alkyl;

R 5 is hydrogen or (C 1-4 )alkyl;

R 3 and R 3 ′ are hydrogen, deuterium, or halogen;

R 6 , R 7 and R 8 are hydrogen, halogen or deuterium;

m is a number selected from 0 to 4,

n is a number selected from 0 to 10, and

p is a number selected from 0 to 10;

with the proviso that n plus p are at least 1.

2. The compound according to claim 1 , wherein

R 2 , R 3 , R 3 ′, R 4 , R 5 , R 6 and R 7 are hydrogen,

X is oxygen,

Y is sulphur,

m is a number selected from 0 to 4, preferably m is 0,

n is a number selected from 0 to 8, preferably from 0 to 7, and

p is a number selected from 0 to 8, preferably from 0 to 7,

with the proviso that n plus p are at least 2, preferably less than 9, and more preferably n plus p is 3 or 4.

3. The compound according to claim 1 , which is selected from the group consisting of

14-O-[((Hydroxy or acyloxy-amino)-cycloalkylsulfanyl- or -cycloalkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins,

14-O-[((Acyl-hydroxy or acyl-acyloxy-amino)-cycloalkylsulfanyl- or -cycloalkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins,

14-O-[((Hydroxy or acyloxy-amino-cycloalkyl)-alkylsulfanyl- or alkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins,

14-O-[(((Acyl-hydroxy or acyl-acyloxy-amino)-cycloalkyl)-alkylsulfanyl- or alkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins,

14-O-[((Hydroxy or acyloxy-amino-cycloalkyloxy)-alkylsulfanyl or alkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins, and

14-O-[(((Acyl-hydroxy or acyl-acyloxy-amino)-cycloalkyloxy)-alkylsulfanyl or alkyl-oxy)-acetyl, -thioacetyl or -imino-oxy]-mutilins.

4. The compound according to claim 1 , which is selected from the group consisting of [(Hydroxy or acyloxy-amino)-cycloalkylsulfanyl]acetic acid mutilin-14-yl ester and [(Acyl-hydroxy or acyl-acyloxy-amino)-cycloalkylsulfanyl]-acetic acid mutilin-14-yl ester.

5. The compound according to claim 1 , which is selected from the group consisting of

[3-(Hydroxyamino)-cyclopentylsulfanyl]acetic acid mutilin-14-yl ester,

[3-(Hydroxyamino)-cyclohexylsulfanyl]acetic acid mutilin-14-yl ester,

[3-(Formyl-hydroxy-amino)-cyclopentylsulfanyl]acetic acid mutilin-14-yl ester,

[3-(Formyl-hydroxy-amino)-cyclohexylsulfanyl]acetic acid mutilin-14-yl ester,

[3-(Acetyl-acetoxy-amino)-cyclohexylsulfanyl]acetic acid mutilin-14-yl ester,

[3-(Acetoxyamino)-cyclohexylsulfanyl]acetic acid mutilin-14-yl ester,

[3-(Isobutyryloxyamino)-cyclohexylsulfanyl]acetic acid mutilin-14-yl ester, and

[3-(Pivaloyloxyamino)-cyclohexylsulfanyl]acetic acid mutilin-14-yl ester.

6. The compound according to claim 1 , in the form of a salt.

7. The compound according to claim 1 , for use as a pharmaceutical.

8. A method of treatment of bacterial diseases which comprises administering to a subject in need of such treatment an effective amount of a compound of claim 1 .

9. A pharmaceutical composition comprising a compound of claim 1 , in association with at least one pharmaceutical excipient.

10. A pharmaceutical composition according to claim 9 , further comprising another pharmaceutically active agent.