Use of nitrooxyderivatives of drug for the treatment of muscular dystrophies

1. A method of treating muscular dystrophies comprising administering to a subject a nitric oxide releasing compound of formula (Ia)

M-X—Y—ONO 2   (Ia)

or enantiomers or diastereoisomers thereof, wherein in the general formula (Ia), M, X and Y have the following meanings:

M is a residue selected from the group consisting of:

X is —O—, —S— or —NR 1 —, wherein R 1 is H or linear or branched C 1 -C 6 alkyl;

Y is a bivalent radical having the following meanings:

a)—straight or branched C 1 -C 20 alkylene being optionally substituted with one or more of the substituents selected from the group consisting of: halogen atoms, hydroxy, —ONO 2 and T, wherein T is —OC(O)(C 1 -C 10 alkyl)-ONO 2 or —O(C 1 -C 10 alkyl) ONO 2 ;

C 5 -C 7 cycloalkylene group optionally substituted with linear or branched C 1 -C 10 alkyl group;

wherein n is an integer from 0 to 20;

n 1 is an integer from 1 to 20 wherein when Y is selected from the bivalent radicals mentioned under b) and c) then the —ONO 2 group of formula is bound to —(CH 2 ) n 1 ;

wherein

X 1 =—OCO— or —COO— and R 2 is H or CH 3 ;

na is an integer from 1 to 20;

n 2 is an integer from 0 to 2;

wherein:

Y 1 is —CH 2 —CH 2 —(CH 2 ) n 2 —; or —CH═CH— (CH 2 ) n 2 ;

X 1 , na, n 2 and R 2 are as defined above;

wherein:

na and R 2 are as defined above, R 3 is H or —COCH 3 ;

wherein when Y is selected from the bivalent radicals mentioned under d)-f) then the —ONO 2 group of formula (I) is bound to —(CH 2 ) na ;

wherein when X is —NR 1 —, wherein R 1 is as above defined Y cannot be f); and

wherein

X 2 is —O— or —S—;

n 3 is an integer from 1 to 6 and

R 2 is as defined above.

2. The method of treating muscular dystrophies according to claim 1 , wherein the compound of formula (Ia) is 2-fluoro-alfa-methyl-4 [1,1′-biphenyl]-4-acetic acid 4-nitrooxybutyl ester of formula (IIIb)

3. The method of treating muscular dystrophies according to claim 1 , wherein in formula (Ia) M is selected from the group consisting of:

X is an oxygen atom,

Y is selected from:

a)—straight C 1 -C 10 alkylene, and

wherein n is an integer from 0 to 5; and

n 1 is an integer from 1 to 5.

4. The method of treating muscular dystrophies according to claim 3 , wherein the compound of formula (Ia) is selected from the group consisting of:

pravastatin 4-(nitrooxy)butyl ester;

pravastatin 4-(nitro-oxymethyl)benzyl ester

atorvastatin 3-(nitrooxy) butyl ester; and

atorvastatin 3-(nitrooxymethyl)benzyl ester

5. The method of treating muscular dystrophies according to claim 1 , wherein Y is a straight or branched C 1 -C 10 alkylene being optionally substituted with one or more of the substituents selected from the group consisting of: halogen atoms, hydroxy, —ONO 2 and T, wherein T is —OC(O) (C 1 -C 10 alkyl)-ONO 2 or —O(C 1 -C 10 alkyl)-ONO 2 .

6. The method of treating muscular dystrophies according to claim 1 wherein Y is a straight or branched C 1 -C 10 alkylene.

7. The method of treating muscular dystrophies according to claim 1 wherein Y is a C 5 -C 7 cycloalkylene group optionally substituted with CH 3 .

8. The method of treating muscular dystrophies according to claim 1 wherein n is an integer from 0 to 5.

9. The method of treating muscular dystrophies according to claim 1 wherein n is 0.

10. The method of treating muscular dystrophies according to claim 1 wherein n 1 is an integer from 1 to 5.

11. The method of treating muscular dystrophies according to claim 1 wherein n 1 is 1.

12. The method of treating muscular dystrophies according to claim 1 wherein preferably na is an integer from 1 to 5.

13. The method of treating muscular dystrophies according to claim 1 , wherein n 3 is an integer from 1 to 4.

14. The method of treating muscular dystrophies according to claim 3 , wherein n 1 is 1.

15. The method of treating muscular dystrophies according to claim 1 , wherein an amount of a nitric oxide releasing compound administered to the subject is from 1 mg to 1000 mg.

16. A method of treating muscular dystrophies consisting of administering to a subject a nitric oxide releasing compound of formula (Ia)

M-X—Y—ONO 2   (Ia)

or enantiomers or diastereoisomers thereof, wherein in the general formula (Ia), M, X and Y have the following meanings:

M is a residue selected from the group consisting of:

X is —O—, —S— or —NR 1 —, wherein R 1 is H or linear or branched

C 1 -C 6 alkyl;

Y is a bivalent radical having the following meanings:

a)—straight or branched C 1 -C 20 alkylene being

optionally substituted with one or more of the substituents selected from the group consisting of: halogen atoms, hydroxy, —ONO 2 and T, wherein T is —OC(O)(C 1 -C 10 alkyl)-ONO 2 or —O(C 1 -C 10 alkyl) ONO 2 ;

C 5 -C 7 cycloalkylene group optionally substituted with linear or branched C 1 -C 10 alkyl group;

wherein n is an integer from 0 to 20;

n 1 is an integer from 1 to 20 wherein when Y is selected from the bivalent radicals mentioned under b) and c) then the —ONO 2 group of formula is bound to —(CH 2 ) n 1 —;

wherein

X 1 =—OCO— or —COO— and R 2 is H or CH 3 ;

na is an integer from 1 to 20;

n 2 is an integer from 0 to 2;

wherein:

Y 1 is —CH 2 —CH 2 —(CH 2 ) n 2 —; or —CH═CH—(CH 2 ) n 2 —;

X 1 , na, n 2 and R 2 are as defined above;

wherein:

na and R 2 are as defined above, R 3 is H or —COCH 3 ;

wherein when Y is selected from the bivalent radicals mentioned under d)-f) then the —ONO 2 group of formula (I) is bound to —(CH 2 ) na ;

wherein when X is —NR 1 , wherein R 1 is as above defined Y cannot be f); and

wherein

X 2 is —O— or —S—;

n 3 is an integer from 1 to 6 and

R 2 is as defined above.

17. The method of treating muscular dystrophies according to claim 16 , wherein the compound of formula (Ia) is 2-fluoro-alfa-methyl-4 [1,1′-biphenyl]-4-acetic acid 4-nitrooxybutyl ester of formula (IIIb)