Macrolide compounds endowed with antiinflammatory activity

1. A compound of formula

wherein

R is a hydrogen atom or a methyl group;

R 1 is a hydrogen atom, an N,N-dimethylamino-N-oxide group, an N-benzyl-N-methylamino group, an N-acetyl-N-methylamino group, an N-[N,N-dimethylamino(C 1 -C 2 )alkylamino]acetyl-N-methylamino group or a chain of formula

wherein

A is a hydrogen atom, a phenyl or a five- or six-membered heteroaryl ring selected from pyrrole, thiophene, furan, imidazole, oxazole, thiazole, pyridine, pyrimidine, triazole and thiadiazole;

X is O or NR 6 and R 6 is a hydrogen atom;

Y is, when n is 0, a C 6 H 4 group or a five- or six-membered heteroaryl ring selected from pyrrole, thiophene, furan, imidazole, oxazole, thiazole, pyridine, pyrimidine, triazole and thiadiazole; or, when n is 1, NR 6 and R 6 is a hydrogen atom;

r is an integer from 1 to 3;

m is the integer 1 or 2;

n is the integer 0 or 1;

or R 1 forms a bond together with R 2 ;

R 2 is a hydrogen atom or forms a bond together with R 1 ;

R 3 is a hydroxy group or forms a group ═N—O—R 5 together with R 4 , and R 5 is a hydrogen atom, a linear or branched C 1 -C 5 alkyl, a benzyl optionally substituted with one or two substituents selected from nitro, hydroxy, carboxy, amino, linear or branched C 1 -C 5 alkyl, C 1 -C 4 alkoxycarbonyl groups, aminocarbonyl groups or cyano groups or a chain of formula

—(CH 2 )r-X—(CH 2 )m-Y—(CH 2 )n-A

wherein

r, m, n, X, Y and A have the meanings given above;

R 4 is a hydrogen atom or forms a group ═N—O—R 5 together with R 3 , and R 5 has the meanings given above;

and the pharmaceutically acceptable salts thereof.

2. A compound according to claim 1 , wherein the oxime group that may be present in position 9 is of E configuration.

3. A compound according to claim 1 , wherein R 1 is a hydrogen atom, an N,N-dimethylamino-N-oxide group, an N-benzyl-N-methylamino group, an N-acetyl-N-methylamino group, an N-[N,N-dimethylaminoethylamino]acetyl-N-methylamino group or a chain of formula

wherein

A is a hydrogen atom, a phenyl or a heteroaryl ring selected from thiophene, furan, thiazole, pyridine and triazole;

X is NR 6 and R 6 is a hydrogen atom;

Y is, when n is 0, a C 6 H 4 group or a heteroaryl ring selected from thiophene, furan, thiazole, pyridine and triazole; or, when n is 1, NR 6 and R 6 is a hydrogen atom;

or R 1 forms a bond together with R 2 .

4. A compound of formula (I):

wherein

R is a hydrogen atom or a methyl group;

R 1 is a hydrogen atom, an N,N-dimethylamino-N-oxide group, an N-benzyl-N-methylamino group, an N-acetyl-N-methylamino group, an N-[N,N-dimethylamino(C 1 -C 2 ) alkylamino]acetyl-N-methylamino group or a chain of formula

wherein

A is a hydrogen atom, a phenyl or a five- or six-membered heteroaryl ring selected from pyrrole, thiophene, furan, imidazole, oxazole, thiazole, pyridine, pyrimidine, triazole and thiadiazole;

X is O or NR 6 and R 6 is a hydrogen atom;

Y is, when n is 0, a C 6 H 4 group or a five- or six-membered heteroaryl ring selected from pyrrole, thiophene, furan, imidazole, oxazole, thiazole, pyridine, pyrimidine, triazole and thiadiazole; or, when n is 1, NR 6 and R 6 is a hydrogen atom;

r is an integer from 1 to 3;

m is the integer 1 or 2;

n is the integer 0 or 1;

or R 1 forms a bond together with R 2 ;

R 2 is a hydrogen atom or forms a bond together with R 1 ;

R 3 is a hydroxy group;

R 4 is a hydrogen atom;

and the pharmaceutically acceptable salts thereof.

5. A compound according to claim 4 , wherein R 1 is a hydrogen atom, an N,N-dimethylamino-N-oxide group, an N-benzyl-N-methylamino group, an N-acetyl-N-methyl amino group, an N-[N,N-dimethylaminoethylamino]acetyl-N-methylamino group or a chain of formula

wherein

A is a hydrogen atom, a phenyl or a heteroaryl ring selected from thiophene, furan, thiazole, pyridine and triazole;

X is NR 6 and R 6 is a hydrogen atom;

Y is, when n is 0, a C 6 H 4 group or a heteroaryl ring selected from thiophene, furan, thiazole, pyridine and triazole; or, when n is 1, NR 6 and R 6 is a hydrogen atom;

or R 1 forms a bond together with R 2 .

6. A process for preparing a compound according to claim 1 , characterized in that the L-cladinose moiety in 3 position is removed from the erythromycin A compounds of formula

wherein R, R 1 , R 2 , R 3 and R 4 are defined as in claim 1 ;

via a hydrolysis reaction.

7. Process according to claim 6 , wherein in formula II R 3 is a hydroxyl group and R 4 is a hydrogen atom.

8. Process according to claim 6 , wherein the removal of the cladinose is performed via an acid hydrolysis reaction catalyzed in the presence of a mineral acid and a protic organic solvent.

9. A compound of formula II:

wherein

R is a hydrogen atom or a methyl group;

R 1 is a hydrogen atom, an N,N-di(C 1 -C 3 )alkylamino group, an N,N-di(C 1 -C 3 )alkylamino-N-oxide group, an N—(C 1 -C 3 )alkyl-N-benzylamino group, an N—(C 1 -C 4 )acyl-N—(C 1 -C 3 )alkylamino group, an N—[N,N-dimethylamino(C 1 -C 4 )alkylamino]acetyl-N—(C 1 -C 3 )alkylamino group

or a chain of formula

wherein

A is a hydrogen atom, a phenyl or a five- or six-membered heteroaryl ring having from one to three hetero atoms selected from nitrogen, oxygen and sulphur;

X is O, S, SO, SO 2 or NR 6 , where R 6 is a hydrogen atom, a linear or branched C 1 -C 3 alkyl, a C 1 -C 3 alkoxycarbonyl group or a benzyloxycarbonyl group;

Y is a C 6 H 4 group, a five- or six-membered heteroaryl ring having from one to three hetero atoms selected from nitrogen, oxygen and sulphur or is O, S, SO, SO 2 or NR 6 where R 6 has the meanings given above;

r is an integer from 1 to 3;

m is an integer from 1 to 6;

n is an integer from 0 to 2;

or R 1 forms a bond together with R 2 ;

R 2 is a hydrogen atom or forms a bond together with R 1 ;

R 3 is a hydroxy group;

R 4 is a hydrogen atom;

and the pharmaceutically acceptable salts thereof;

provided, however, that (i) R 1 is not an N,N-dimethyl amino group, and (ii) R 1 is not an N,N-dimethyl amino-N-oxide group when R is a hydrogen atom,

and provided that one of the following limitations is met:

R is a hydrogen atom and R 1 forms a bond together with R 2 ;

R is a hydrogen atom and R 1 is an N-benzyl-N-methylamino group;

R is a hydrogen atom and R 1 is an N-acetyl-N-methylamino group;

R is a hydrogen atom and R 1 is an N—[N,N-dimethylaminoethvlamino]acetyl-N-methyl amino group;

R is a hydrogen atom and R 1 is an N-methyl-N-3-[(2-thiazolylmethyl)amino]propylamino group;

R is a hydrogen atom and R 1 is an N-2-[2-[(2-thiazolylmethyl)amino]ethylamino]ethyl-N-methylamino group; and

R is a hydrogen atom and R 1 is an N-2-[2-(benzylamino)ethylamino]ethyl-N-methylamino group.

10. A compound according to claim 9 , wherein R is a hydrogen atom and R 1 forms a bond together with R 2 .

11. A compound according to claim 9 , wherein R is a hydrogen atom and R 1 is an N-benzyl-N-methylamino group.

12. A compound according to claim 9 , wherein R is a hydrogen atom and R 1 is an N-acetyl-N-methylamino group.

13. A compound according to claim 9 , wherein R is a hydrogen atom and R 1 is an N-[N,N-dimethylaminoethylamino]acetyl-N-methyl amino group.

14. A compound according to claim 9 , wherein R is a hydrogen atom and R 1 is an N-methyl-N-3-[(2-thiazolylmethyl)amino]propylamino group.

15. A compound according to claim 9 , wherein R is a hydrogen atom and R 1 is an N-2-[2-[(2-thiazolylmethyl)amino]ethylamino]ethyl-N-methylamino group.

16. A compound according to claim 9 , wherein R is a hydrogen atom and R 1 is an N-2-[2-(benzylamino)ethylamino]ethyl-N-methylamino group.

17. The compound de(N-methyl)-9-dihydroerythromycin A.

18. The compound de(N-methyl)-descladinosyl-9-dihydro-erythromycin A.

19. A process for preparing a compound according to claim 4 , wherein the L-cladinose moiety in 3 position is removed from the erythromycin A compounds of formula

wherein R, R 1 , R 2 , R 3 and R 4 are defined as in claim 4 ;

via a hydrolysis reaction.

20. Process according to claim 19 , wherein the removal of the cladinose is performed via an acid hydrolysis reaction catalyzed in the presence of a mineral acid and a protic organic solvent.