Pleuromutilin derivatives as antimicrobials

1. A compound of formula

wherein

R 1 and R 1 ′ are hydrogen or deuterium,

R 2 , R 3 and R 4 are hydrogen or deuterium,

R 5 is the residue of an alpha amino acid, wherein the N which is part of the ring in formula I is acylated by the carboxylic group of said amino acid and wherein the carbonyl group of said amino acid is bound to the nitrogen of the group of formula

 and the —OH group of said amino acid function is missing,

X is S or N-ALK, the group of formula

 is piperidinyl or tetrahydropyridinyl,

ALK is (C 1-4 )alkyl, and

R 6 is hydrogen, hydroxy or (C 2-12 )acyloxy,

with the proviso that if the group

 is piperidinyl and X is S, then R 6 is other than hydrogen.

2. A compound according to claim 1 which is selected from the group consisting of

14-O-[4-hydroxy-N-valyl-piperidin-3-yl]-sulfanylacetylmutilin,

14-O-[3-hydroxy-N-valyl-piperidin-4-yl]-sulfanylacetylmutilin,

14-O-[3-hydroxy-N-histidinyl-piperidin-4-yl]-sulfanylacetylmutilin,

14-O-[3-hydroxy-N-valyl-piperidin-4-yl]-methylaminoacetylmutilin,

14-O-[4-hydroxy-N-valyl-piperidin-3-yl]-methylaminoacetylmutilin,

14-O—[N-valyl)-1,2,3,6-tetrahydropyridin-3-yl]-sulfanylacetylmutilin, and

14-O—[N-valyl)-1,4,5,6-tetrahydropyridin-4-yl]-sulfanylacetylmutilin.

3. A compound of formula

wherein

R 1 and R 1 ′ are hydrogen or deuterium,

R 2 , R 3 and R 4 are hydrogen or deuterium,

R 7 is a protecting group or the residue of an alpha amino acid, wherein the N which is part of the ring in formula II is acylated by the carboxylic group of said amino acid and wherein the carbonyl group of said amino acid is bound to the nitrogen of the group of formula

 and said amino acid function is devoid of the —OH group, and wherein the amino group is protected,

X is S or N-ALK, the group of formula

 is piperidinyl or tetrahydropyridinyl,

ALK is (C 1-4 )alkyl, and

R 8 is hydrogen, hydroxy or (C 2-12 )acyloxy,

with the proviso that if the group of formula

 is piperidinyl and X is S, then R 8 is other than hydrogen.

4. A compound according to claim 3 selected from the group consisting of

14-O—[N-BOC-4-hydroxy-piperidin-3-yl]-sulfanylacetylmutilin,

14-O—[N-BOC-3-hydroxy-piperidin-4-yl]-sulfanylacetylmutilin,

14-O-[4-hydroxy-N-BOC-piperidin-3-yl]-methylaminoacetylmutilin,

14-O-[3-hydroxy-N-BOC-piperidin-4-yl]-methylaminoacetylmutilin,

14-O—[N-BOC-1,4,5,6-tetrahydropyridin-4-yl]-sulfanylacetylmutilin,

14-O-[4-hydroxy-N—(N-BOC-valyl)-piperidin-3-yl]-sulfanylacetylmutilin,

14-O-[3-hydroxy-N—(N-BOC-valyl)-piperidin-4-yl]-sulfanylacetylmutilin,

14-O-[4-acetoxy-N—(N-BOC-valyl)-piperidin-3-yl]-sulfanylacetylmutilin,

14-O-[3-acetoxy-N—(N-BOC-valyl)-piperidin-4-yl]-sulfanylacetylmutilin,

14-O-[3-hydroxy-N—(N-BOC-histidinyl)-piperidin-4-yl]-sulfanylacetylmutilin,

14-O-[3-hydroxy-N—(N-BOC)-valyl-piperidin-4-yl]- methylaminoacetylmutilin,

14-O-[4-hydroxy-N—(N-BOC)-valyl-piperidin-3-yl]- methylaminoacetylmutilin,

14-O—[N—(N-BOC-valyl)-1,4,5,6-tetrahydropyridin-4-yl]- sulfanylacetylmutilin,

14-O—[N—(N-BOC-valyl)-1,2,3,6-tetrahydropyridin-3-yl]- sulfanylacetylmutilin.

5. A compound of claim 1 in the form of a salt.

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

7. A pharmaceutical according to claim 6 further comprising another pharmaceutically active agent.

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