PLEUROMUTILIN DERIVATIVES FOR THE TREATMENT OF DISEASES MEDIATED BY MICROBES

1 . A compound of formula (I)

wherein

n is 0 to 4;

m is 0 or 1 with the proviso that the sulphur atom and R 3 are in vicinal position (if m=0 then R 3 is in position 2′, and if m=1 then R 3 is on position 1′);

R is ethyl or vinyl;

R 1 is hydrogen or (C 1-6 )alkyl,

R 2 is hydrogen or

(C 3-6 )cycloalkyl, or

unsubstituted (C 1-6 )alkyl, or

(C 1-6 )alkyl substituted by one or more of

hydroxy, preferably one or two,

methoxy,

halogen,

(C 3-6 )cycloalkyl, or

R 1 and R 2 together with the nitrogen atom to which they are attached form a 5 to 7 membered heterocyclic ring containing at least 1 nitrogen atom or 1 nitrogen and 1 additional heteroatome e. g. selected from N or O, or

R 1 is hydroxy and R 2 is formyl;

R 3 is OH, OR 4 , a halogen atom, or

with the proviso that R 3 is bound to 2′ R 3 represents —O—(CH 2 ) p —O— with p is 2 or 3;

R 4 is unsubstituted (C 1-6 )alkyl or (C 3-6 )cycloalkyl.

2 . A compound of formula (II)

wherein n, R, R 1 , R 2 and R 3 are as defined in claim 1 .

3 . A compound of formula (III)

wherein n, R, R 1 and R 2 are as defined in claim 1 .

4 . A compound of formula (IV)

wherein n, R 1 and R 2 are as defined in claim 1 .

5 . A compound of formula (V)

wherein n, R 1 and R 2 are as defined in claim 1 .

6 . A compound of formula (VI)

wherein n, R 1 and R 2 are as defined in claim 1 .

7 . A compound according to one of the claims 1 to 6 , selected from the group consisting of

14-O-{[(1R,2R,4R)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin

14-O-{[(1S,2S,4S)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin

14-O-{[(1R,2R,5S)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin

14-O-{[(1S,2S,5R)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin

14-O-{[(1R,2R,4S)-4-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S,4R) diastereomer thereof

14-O-{[(1R,2R,5R)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin

14-O-{[(1S,2S,5S)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin

14-O-{[(1R,2R,3R)-3-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S,3S) diastereomer thereof

14-O-{[(1R,2R,4R)-4-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,4S) diastereomer thereof

14-O-{[(1R,2R,4R)-4-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,4S) diastereomer thereof

14-O-{[(1R,2R,5S)-5-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5R) diastereomer thereof

14-O-{[(1R,2R,5S)-5-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5R) diastereomer thereof

14-O-{[(1R,2R,4S)-4-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,4R) diastereomer thereof

14-O-{[(1R,2R,5R)-5-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5S) diastereomer thereof

14-O-{[(1R,2R,3R)-3-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,3S) diastereomer thereof

14-O-{[(1R,2R,3R)-3-Diethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,3S) diastereomer thereof

14-O-{[(1R,2R,4S)-4-(Formyl-hydroxy-amino)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,4R) diastereomer thereof

14-O-{[(1R,2R,5S)-5-(Formyl-hydroxy-amino)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5R) diastereomer thereof

14-O-{[(1R,2R,3R/S)-3-(Formyl-hydroxy-amino)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,3R/S) diastereomer thereof

14-O-{[(1R,2R,5S)-2-Hydroxy-5-methylamino-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5R) diastereomer thereof

14-O-{[(1R,2R,5S)-5-Allylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5R) diastereomer thereof

14-O-{[(1R,2R,5S)-2-hydroxy-5-(2-methoxy-ethylamino)-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5R) diastereomer thereof

14-O-{[(1R,2R,4R*)-2-Hydroxy-4-(2-hydroxy-ethylamino)-cyclohexylsulfanyl]acetyl}-mutilin and the (1S,2S,4S*) diastereomer thereof

14-O-{[(1R,2R,4R*)-4-Cyclohexylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,4S*) diastereomer thereof

14-O-{[(1R,2R,4R*)-4-Cyclopropylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,4S*) diastereomer thereof

14-O-{[(1R,2R,5S*)-4-Cyclopropylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5R*) diastereomer thereof

14-O-{[(1R,2R,4S*)-4-Cyclopropylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,4R*) diastereomer thereof

14-O-{[(1R,2R,5R*)-2-Hydroxy-5-morpholin-4-yl-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5S*) diastereomer thereof

14-O-{[(1R,2R,5S*)-2-Hydroxy-5-morpholin-4-yl-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S,5R*) diastereomer thereof

14-O-{[(1R,2R,5S)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-19,20-dihydro-mutilin and the (1S,2S,5R) diastereomer thereof

14-O-{[(1R,2R,5S)-5-Ethylamino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-19,20-dihydro-mutilin and the (1S,2S,5R) diastereomer thereof

14-O-{[(1R,2R,5R)-5-Amino-2-hydroxy-cyclohexylsulfanyl]-acetyl}-19,20-dihydro-mutilin and the (1S,2S,5S) diastereomer thereof

14-O-{[(1R,2R)-4-Aminomethyl-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S, 2S) diastereomers thereof

14-O-{[5-Amino-2-chloro-cyclohexylsulfanyl]-acetyl}-mutilin

14-O-{[4-Amino-2-chloro-cyclohexylsulfanyl]-acetyl}-mutilin

14-O-{(4-Amino-1-hydroxy-cyclohexylmethylsulfanyl)-acetyl}-mutilin

14-O-{[(1R,2R)-2-Hydroxy-5-(3-methylamino-propyl)-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S) diastereomers thereof

14-O-{[(1R,2R)-2-Hydroxy-4-(3-methylamino-propyl)-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S) diastereomers thereof

14-O-{[(1R,2R)-5-(3-Amino-propyl)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S) diastereomers thereof

14-O-{[(1R,2R)-4-(3-Amino-propyl)-2-hydroxy-cyclohexylsulfanyl]-acetyl}-mutilin and the (1S,2S) diastereomer thereof

14-O-{[(6R,8R)-8-Amino-1,4-dioxo-spiro[4.5]dec-6-ylsulfanyl]-acetyl}-mutilin and the (6S, 8S) diastereomer thereof

14-O-{[(4-Amino-2-methoxy-cyclohexylsulfanyl]-acetyl}-mutilin

and

14-O-{[(5-Amino-2-methoxy-cyclohexylsulfanyl]-acetyl}-mutilin

8 . The compound according to any of claims 1 to 7 in the form of a salt and/or solvate.

9 . A compound according to any of claims 1 to 8 for use as a pharmaceutical drug substance.

10 . A method of treatment of diseases mediated by microbes which comprises administering to a subject in need of such treatment an effective amount of a compound of any one of claims 1 to 8 .

11 . A pharmaceutical drug composition comprising a compound of anyone of claims 1 to 8 , in association with at least one pharmaceutical excipient.

12 . A pharmaceutical drug composition according to claim 11 , further comprising another pharmaceutically active agent.