Macrolides and their use

Macrolide compound of formula I:

• wherein
• R1 is a residue -Y-X-Q;
• Y is S, SO or SO2;
• X is a bond or a linear group consisting of hydrogen atoms and 1 to 9 atoms selected from C, N, O and S, of which up to 2 atoms can be N and one atom can be O or S, one carbon atom can appear as a CO group and the sulphur atom can appear as an SO2 group and two adjacent C atoms can be present as —CH═CH— or —C≡C— and which group X is unsubstituted or is substituted with —COO—W or —CONH—W;
• Q is a residue —V-A1-L-A2-W or, if X does not represent a bond, may also be —NR10R11
• V is an optionally substituted divalent aromatic or heterocyclic group;
• W is optionally substituted aryl or heterocyclyl;
• A1 and A2 are, independently of each other, either absent or a C1-C4alkylene group;
• L is —O—, —S—, —SO2—, —NH—, —CO—, —(CO)O—, —O(OC)—, —(CO)NH—, —NH(CO)—, —(SO2)NH—, —HN(SO2)—, —HN(CO)NH—, —O(CO)NH—, —NH(CO)O—, or can also be absent if A1 and/or A2 are present;
• R2 is OR2a or
• wherein
• represents the bond between said group and the carbon atom of said macrolide compound to which it is linked;
• R2a is hydrogen, acetyl, —(C═O)CH2NR2bR2c, or —(C═O)CH2CH2NR2bR2c;
• R2b and R2c independently of each other, are hydrogen or C1-C6 alkyl which can be substituted or unsubstituted and wherein up to two atoms can be N, O or S and one carbon atom can appear as C═O or, taken together with the nitrogen atom to which they are linked, form a 4-7 membered-ring of which up to two atoms can be N, O or S and one carbon can appear as C═O;
• R3 is hydrogen or
• R2 and R3 taken together with the carbon atom to which they are linked, represent a C═O group;
• R4 is hydrogen or
• R2 and R4 taken together with the bond between the carbon atoms to which they are linked, represent a double bond between said carbon atoms;
• Z is
• wherein
• represents the bond between said group and the carbon atom of said macrolide compound to which it is linked;
• R5 is hydrogen or —OR5a or —NR5bR5c;
• R6 is hydrogen or —OR6a or —NR6bR6c;
• or
• R5 and R6 taken together with the carbon atom to which they are linked, represent a C═O group;
• R7 is hydrogen or —OR7a or —NR7bR7c;
• R8 is hydrogen or —OR8a or —NR8bR8c;
• or
• R7 and R8 taken together with the carbon atom to which they are linked, represent a C═O group;
• or one of
• R5 and R6 taken together with one of
• R7 and R8 represent a group of formula —NR56(CO)O— or —O(CO)NR78—
• R9 is hydrogen or
• R8 and R9 taken together with the bond between the carbon atoms to which they are linked, represent a double bond between said carbon atoms;
• R5a,
• R7a and R8a, independently of each other, are hydrogen or C1-C6 alkyl which can be substituted or unsubstituted and wherein one or more single bonds can be replaced by double and/or triple bonds and where one carbon atom can appear as C═O and up to two atoms can be N, O or S;
• R6a is hydrogen or C1-C6 alkyl;
• R56 and R78 are hydrogen or C1-C6 alkyl;
• R5b, R5c,
• R6b, R6c,
• R7b, R7c,
• R8b and R8c independently of one another, are hydrogen, C1-C6alkyl which can be substituted or unsubstituted and up to two atoms can be N, O or S and where one carbon atom can appear as C═O, or —(C═O)heterocyclyl or, taken together with the nitrogen atom to which they are linked, form a 4-7 membered-ring of which up to two atoms can be N, O or S and one carbon can appear as C═O;
• R10 and R11 are independently selected from optionally substituted groups selected from aryl;
• aralkyl;
• heterocyclyl and heterocyclylalkyl;
• groups, and one of R10 and R11 can also be a group -L-A2-W;
• and
• * indicates a chiral centre which is in the (R) or (S) form;
• provided that
• Z is not a group of formula
• wherein
• represents the bond between said group and the carbon atom of said macrolide compound to which it is linked,
• or an acid addition salt, a N-oxide or an in vivo cleavable ester thereof.