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1. WO2006000294 - NOUVEAUX COMPOSES DIAZENIUMDIOLATE, PROCEDE DE PREPARATION CORRESPONDANT ET UTILISATION THERAPEUTIQUE DE CES DERNIERS

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[ EN ]
CLAIMS

1. Compounds of the formula (I):


in which:
- m is an integer between 0 and 3;
■ n is an integer between 0 and 1 ;
■ p is an integer between 1 and 7;
- X represents an oxygen atom -O-, a group -NR1- or, if n = 0, X represents a single bond; in which
R1 represents a hydrogen atom or an -alkyl or -aryl group, each optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2, per- fluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl
Y represents -CH2-;
- Ar represents a phenyl group;
Ar is optionally substituted by 1 to 3 substituents A, in which
two of the substituents A can represent a heterocycle fused to the phenyl, such as benzodioxolane, or in which;
- each of the substituents A independently represents a group chosen from:
° -OH;
° -CN;
» -Hal;
c Ci-C6 -alkyl, optionally substituted by one or more groups chosen from -OH,

-Oalkyl, -CN, -NO2, perfluoroalkyl and-NR2R3, in which
R2 represents H, -alkyl and R3 represents -alkyl, -aryl;

° -alkyl-O-aryl, in which aryl is optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR"2 R"3, in which R"2 represents H, -alkyl or -NO and R"3 represents -alkyl or -aryl;

° -Oalkyl, optionally substituted by one or more groups chosen from -OH,

-Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -Oalkylaryl, optionally substituted by one or more groups chosen from -OH, -alkyl, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -Oaryl optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR'2R'3, in which
R'2 represents H or -alkyl and R'3 represents -alkyl, -aryl, -C(=O)alkyl or -C(=O)aryl;

° -O(alkyl)r-C(=O)-R7, in which
r represents O or 1 ,
R7 represents an -alkyl, -OR8 or NR9R10 group; in which
R8 represents a hydrogen atom or an -alkyl group;
R9 and R10 independently represent a hydrogen atom or an -alkyl,

-alkenyl, -N=alkyl or -N=alkenyl group, in which the alkyl or alkenyl group is optionally substituted by one or more groups chosen from -aryl and -Het, which are themselves optionally substituted by one or more groups chosen from a halogen atom and an -OH, -alkyl or -Oalkyl group;

° -Oalkyl-O-R11 , in which
R11 represents a group as follows:
-alkyl,
-aryl optionally substituted by one or more groups chosen from -OH,

-alkyl and -Oalkyl,
-alkylaryl, -C(=O)alkyl, optionally substituted by one or more groups chosen from -aryl and -Het;
-C(=O)alkenyl, optionally substituted by -aryl or -Het;
-C(=O)NR12R13, in which R12 and R13 independently represent a hydrogen atom or an -alkyl group;

° -N(NO)-aryl, optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -NR4R5, in which
R4 represents H or alkyl and R5 represents -alkyl, -aryl or -alkylaryl, in which the -aryl group is optionally substituted by one or more groups chosen from -OH, -alkyl, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR'2R'3, in which
R'2 represents H or -alkyl and R'3 represents -alkyl, -aryl, -C(=O)alkyl or -C(=O)aryl;

» -S(O)qR6, in which
q represents 0, 1 or 2,
R6 represents an -alkyl or -aryl group, each optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2-, perfluoroalkyl, -alkyl, -Oalkyl and -NR14R15, in which
R14 and R15 independently represent a hydrogen atom or an -alkyl, -C(=O)alkyl, -C(=O)aryl or -C(=O)Het group, in which, in these last three cases, alkyl, aryl and Het may be optionally substituted by one or more groups chosen from -OH, -CN, -Oalkyl, -NO2, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -perfluoroalkyl;
° -Het;
° -alkylHet;
° -OHet;

or the corresponding salts,
and also the enantiomers, diastereoisomers, racemic mixtures and pharmaceutically acceptable salts;

with the exception of the compounds for which:

1) n = 0, p = 1 , Ar represents a -phenyl group, Y = -CH2-, and
m = 0 or
m = 1 , and A represents a 4-tert-Bu, 4-OMe, 4-CI, 4-OH1 3-OH, 2-OH, 3-CI, 2-F, 3-Me, 4-Me, 4-NMe2 or 4-CN group, or
m = 2, and A represents a 2,4-di OH or 2,5-di OH group;
2) n = 0, p = 3, Ar represents a -phenyl group, Y = -CH2-, and m = 0.

2. Compounds according to Claim 1 , such that they are represented by formula (I'):

(A)m-Ar-(X)n-(Y)p-N-O- M+ (V)
in which A, Ar, X, Y, m, n and p are as defined in Claim 1 and M+ represents a cation.

3. Compounds according to Claim 2, such that M+ is chosen from NH4+ and an alkali metal cation.

4. Compounds according to Claim 1 or 2, such that X represents a single bond, -O- or -NR1-, in which R1 represents an optionally substituted -aryl group and A, Ar, Y, m, n and p are as defined according to any one of the preceding claims.

5. Compounds according to any one of the preceding claims, such that each of the groups A independently represents a group chosen from
-S(O)q-R6, in which q=0 and R6 represents an -aryl group optionally substituted by one or more groups chosen from -Oalkyl,
- -Oalkyl, -OalkyleORH , in which
R11 represents
a -C(=O)alkenyl group, in which alkenyl is optionally substituted by Het, or
an -aryl group optionally substituted by one or more groups chosen from -OH and -alkyl,
an -Oaryl group, in which aryl is optionally substituted by one or more groups chosen from -Oalkyl,
-NR4R5, in which R4 represents an -alkyl group and R5 represents an -aryl group, optionally substituted by -Oalkyl,
-alkyl-O-aryl, in which aryl is optionally substituted by -NR"2R"3, in which R"2 represents a hydrogen atom or an -N=O group, and R"3 represents an -aryl group;

« -Oalkylaryl, in which aryl is optionally substituted by one or more groups chosen from -OH and -alkyl;
-Oalkyl-C(=O)R7, in which R7 represents -NR9R10, in which R9 represents H and

R10 represents -N=alkyl or -N=alkenyl, in which the -alkyl or -alkenyl group is optionally substituted by one or more groups chosen from -aryl and -Het, which are themselves optionally substituted by one or more groups chosen from -Oalkyl, -OH and -Hal;
-alkyl,
- -Hal,
■ -OH,
-N(NO)-aryl,
or in which two of the groups A form with phenyl a fused heterocycle, for example a dioxolane group.

6. Compounds according to any one of the preceding claims, such that p = 1 , n = 0, and Y, Ar, A and m are defined according to any one of the preceding claims.

7. Compounds according to Claim 6, such that Ar represents a -phenyl- group, m = 1 and A represents
an -Oaryl group, in which aryl is optionally substituted by one or more groups chosen from -Oalkyl, -S-aryl optionally substituted by one or more -Oalkyl,
- -N(alkyl)-aryl is substituted by -Oalkyl,
- -alkyl-O-aryl, in which aryl is optionally substituted by -NR"2R"3, in which R"2 and R"3 are as defined above,
- -Oalkylaryl,
-Oalkyl, in which alkyl is C2-C6
-Oalkyl-C(=O)R7, in which R7 represents -NR9R10, in which R9 represents H and R10 represents -N=Nalkyl or -N=Nalkenyl, in which the alkyl or alkenyl group is optionally substituted by one or more groups chosen from -aryl and -Het, which are themselves optionally substituted by one or more groups chosen from -Oalkyl,

-OH and -Hal,
or m = 2, 3, 4 or 5 and each of the groups A is independently chosen from

-Oalkyl, -alkyl, -Hal and -OH, or in which two of the groups A form a heterocycle fused with phenyl, for example a benzodioxolane group.

8. Compounds according to any one of the preceding claims, such that p = 1 , n=1 and Ar, A, X and Y are defined according to any one of the preceding claims.

9. Compounds according to Claim 8, such that Y = -alkyl-, X = -O- or -NR1-, in which R1 represents an -aryl group optionally substituted by -NO2, Ar represents a

-phenyl- group, m = 1 and A represents -N(NO)-aryl or -Oalkyl.

10. Compounds according to any one of the preceding claims, such that the compounds of the formula (I) or (I1) are chosen from:
ammonium 1-[4-(4-methoxyphenoxy)benzyl]-2-oxohydrazinolate;
ammonium 1-{4-[(4-methoxyphenyl)thio]benzyl}-2-oxohydrazinolate;
ammonium 1 -(2,4-dimethoxybenzyl)-2-oxohydrazinolate;
ammonium 1-[4-(benzyloxy)benzyl]-2-oxohydrazinolate;
ammonium 1-(4-butoxybenzyl)-2-oxohydrazinolate;
ammonium 1-(1 ,3-benzodioxol-5-ylmethyl)-2-oxohydrazinolate;
ammonium 2-oxo-1-(2,3,4-trimethoxybenzyl)hydrazinolate;
ammonium 1 -(4-methoxy-3-methylbenzyl)-2-oxohydrazinolate;
ammonium 1 -(3,4-dimethoxybenzyl)-2-oxohydrazinolate;

ammonium 1 -(3-fluoro-4-methoxybenzyl)-2-oxohydrazinolate;
ammonium 1-(3,5-di-tert-butyl-4-hydroxybenzyl)-2-oxohydrazinolate;
2,6-di-tert-butyl-4-[2-(4-{[methoxy(nitroso)amino]methyl}phenoxy)ethyI]phenol; ammonium 1-{4-[(4-methoxyphenyl)(methyl)amino]benzyl}-2-oxohydrazinolate; ammonium 1 -{2-[(4-anilinophenoxy)methyl]benzyl}-2-oxohydrazinolate;
4-[(2-{[hydroxy(nitroso)amino]methyl}benzyl)oxy]phenyl}nitroso(phenyl)amine; ammonium 1-(7-{4-[nitroso(phenyl)amino]phenoxy}heptyl)-2-oxohydrazinolate; ammonium 1-{5-[(4-methoxyphenyl)(4-nitrophenyl)amino]pentyl}-2-oxohydrazino-late;
ammonium 1 -(4-{2-[(2E)-2-(2-hydroxy-4-methoxybenzylidene)hydrazino]-2-oxo-ethoxy}benzyl)-2-oxohydrazinolate;
ammonium 2-oxo-1-(4-{2-oxo-2-[(2E)-2-(pyridin-3-ylmethylene)hydrazino]ethoxy}-benzyl)hydrazinolate;
N'-[(1 E)-(5-chloro-2-hydroxyphenyl)methylene]-2-(4-{[hydroxy(nitroso)amino]-methyl}phenoxy)acetohydrazide;
ammonium 1-(4-{2-[(2E)-2-benzylidenehydrazino]-2-oxoethoxy}benzyl)-2-oxo-hydrazinolate;
ammonium 2-oxo-1 -[4-(2-oxo-2-{(2E)-2-[(2E)-3-phenylprop-2-en-1 -ylidene]-hydrazino}ethoxy)benzyl]hydrazinolate;
in free form or in the form of a salt thereof, and also the enantiomers, diastereo-isomers, racemic mixtures and pharmaceutically acceptable salts.

11. Compounds according to any one of the preceding claims, such that the compounds of the formula (I) or (I1) are chosen from:
ammonium 1-{2-[(4-anilinophenoxy)methyl]benzyl}-2-oxohydrazinolate;
ammonium 1-{5-[(4-methoxyphenyl)(4-nitrophenyl)amino]pentyl}-2-oxohydrazino-late;
ammonium 1-(4-{2-[(2E)-2-(2-hydroxy-4-methoxybenzylidene)hydrazino]-2-oxo of ethoxy}benzyl)-2-oxohydrazinolate;
in free form or in the form of a salt thereof, and also the enantiomers, diastereo-isomers, racemic mixtures and pharmaceutically acceptable salts.

12. Process for the preparation of a compound according to any one of the preceding claims, comprising the step consisting in performing a nitrosation on the -NH-OH group of a corresponding compound.

13. Process according to Claim 12, such that the process is performed using the corresponding products of the formula (II):
(A)m-Ar-(X)n-(Y)p-N-OH
H (H)
in which A, Ar, Y, m, n and p are as defined according to any one of Claims 1 to 11 , using a compound of nitrite type.

14. Process according to Claim 13, such that the compound of nitrite type is an alkyl nitrite or an alkali metal nitrite.

15. Process according to Claim 14, such that the nitrite is chosen from tert-butyl nitrite and ethyl nitrite, or sodium or potassium nitrite.

16. Process according to any one of Claims 12 to 15, such that ammonia gas is reacted.

17. Process according to any one of Claims 12 to 16, also comprising the step of preparing the free form of compound (I) from the corresponding salt.

18. Process according to Claim 17, such that it is performed by addition of base.

19. Compounds of the formula (II):
(A)m-Ar-(X)n-(Y)p-N-OH
H (H)
in which A, Ar, Y, m, n and p are as defined according to any one of Claims 1 to 11.

20. Process for the preparation of the compounds of the formula (II) according to Claim 19, such that it is performed by reduction starting with the corresponding compounds of the formula (III):
(A)m-Ar-(X)n-(Y)p-NO2 (|||)

in which A1 Ar, Y, m, n and p are as defined according to any one of Claims 1 to 11.

21. Process according to Claim 20, such that it is performed using zinc, in the presence of NH4CI, in a suitable solvent medium, at a temperature of between room temperature and the reflux temperature of the solvent.

22. Process according to Claim 20, such that it is performed using hydrazine hydrate, in the presence of a catalyst, such as Raney nickel, in a suitable solvent medium, at a temperature of between O0C and room temperature.

23. Process for the preparation of the compounds of the formula (II) according to Claim 19, such that it is performed by reduction starting with the corresponding compounds of the formula (IV):
(A)m-Ar-(X)n-(Y)p = N-OH (IV)
in which A, Ar, X, Y, m, n and p are as defined according to any one of Claims 1 to 11.

24. Process according to Claim 23, such that it is performed using sodium borohydride NaBH4, in the presence of acid, in a suitable solvent medium, at a temperature of between 00C and room temperature.

25. Process according to Claim 23, such that it is performed using NaCNH3 in the presence of acid, in a suitable solvent medium, at a temperature of between 00C and room temperature.

26. Process according to any one of Claims 12 to 25, also comprising the step consisting in isolating the product obtained of the formula (I), (I1) or (II).

27. Pharmaceutical compositions comprising a compound according to any one of Claims 1 to 11 and pharmaceutically acceptable vehicle or excipient.

28. Use of a compound of the formula (I):

N'
(A) -Ar-(X)n-(Y) -N- -OOHH
(I)

in which:
m is an integer between O and 3;
n is an integer between O and 1 ;
p is an integer between 1 and 7;
- X represents an oxygen atom -O-, a group -NR1- or, if n = 0, X represents a single bond; in which
R1 represents a hydrogen atom or an -alkyl or -aryl group, each optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2, per- fluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl
Y represents -CH2-;
- Ar represents a phenyl group;
Ar is optionally substituted by 1 to 3 substituents A, in which
two of the substituents A can represent a heterocycle fused to the phenyl, such as benzodioxolane, or in which;
each of the substituents A independently represents a group chosen from:
° -OH;
° -CN;
0 -Hal;
° Ci-C6 -alkyl, optionally substituted by one or more groups chosen from -OH,

-Oalkyl, -CN, -NO2, perfluoroalkyl and-NR2R3, in which
R2 represents H, -alkyl and R3 represents -alkyl, -aryl;

° -alkyl-O-aryl, in which aryl is optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR"2 R"3, in which
R"2 represents H, -alkyl or -NO and R"3 represents -alkyl or -aryl;

° -Oalkyl, optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -Oalkylaryl, optionally substituted by one or more groups chosen from -OH,

-alkyl, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -Oaryl optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR'2R'3, in which
R'2 represents H or -alkyl and R'3 represents -alkyl, -aryl, -C(=O)alkyl or -C(=O)aryl;

° -O(alkyl)r-C(=O)-R7, in which
r represents O or 1 ,
R7 represents an -alkyl, -OR8 or NR9R10 group; in which
R8 represents a hydrogen atom or an -alkyl group;
R9 and R10 independently represent a hydrogen atom or an -alkyl, -alkenyl, -N=alkyl or -N=alkenyl group, in which the alkyl or alkenyl group is optionally substituted by one or more groups chosen from

-aryl and -Het, which are themselves optionally substituted by one or more groups chosen from a halogen atom and an -OH, -alkyl or -Oalkyl group;

° -Oalkyl-O-R11 , in which
R11 represents a group as follows:
-alkyl, -aryl optionally substituted by one or more groups chosen from -OH, -alkyl and -Oalkyl,
-alkylaryl,
-C(=O)alkyl, optionally substituted by one or more groups chosen from -aryl and -Het;
-C(=O)alkenyl, optionally substituted by -aryl or -Het;
-C(=O)NR12R13, in which R12 and R13 independently represent a hydrogen atom or an -alkyl group;

° -N(NO)-aryl, optionally substituted by one or more groups chosen from -OH,

-Oalkyl, -CN, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -NR4R5, in which
R4 represents H or alkyl and R5 represents -alkyl, -aryl or -alkylaryl, in which the -aryl group is optionally substituted by one or more groups chosen from -OH, -alkyl, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR'2R'3, in which
R'2 represents H or -alkyl and R'3 represents -alkyl, -aryl, -C(=O)alkyl or -C(=O)aryl;

° -S(O)qR6, in which
q represents 0, 1 or 2,
R6 represents an -alkyl or -aryl group, each optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2-, perfluoroalkyl, -alkyl, -Oalkyl and -NR14R15, in which
R14 and R15 independently represent a hydrogen atom or an -alkyl, -C(=O)alkyl, -C(=O)aryl or -C(=O)Het group, in which, in these last three cases, alkyl, aryl and Het may be optionally substituted by one or more groups chosen from -OH, -CN, -Oalkyl, -NO2, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -perfluoroalkyl;

° -Het;
- -alkylHet;
° -OHet;
or the corresponding salts,
and also the enantiomers, diastereoisomers, racemic mixtures and pharmaceutically acceptable salts,
for the preparation of pharmaceutical compositions for inhibiting the proliferation of smooth muscle cells.

29. Use of a compound of the formula (I) according to Claim 28 for the preparation of pharmaceutical compositions for the prevention and/or treatment of vascular pathologies associated with the proliferation of smooth muscle cells.

30. Use according to Claim 29, such that the said pathologies are chosen from atherosclerosis, restenosis and stenosis.

31. Use according to Claim 29, such that the said pathologies are complications associated with angioplasty with or without a stent, bypass surgery or transplants.

32. Use of a compound of the formula (I):
.0
N '
(A)m-Ar-(X)n-(Y)p-N- -OnHμ
(I)
in which:
■ m is an integer between 0 and 3;
« n is an integer between 0 and 1 ;
- p is an integer between 1 and 7;
■ X represents an oxygen atom -O-, a group -NR1- or, if n = 0, X represents a single bond; in which
R1 represents a hydrogen atom or an -alkyl or -aryl group, each optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2, per- fluoroalkyl and -NR2R3, in which R2 represents H or -alkyl and R3 represents -alkyl or -aryl
- Y represents -CH2-;
Ar represents a phenyl group;
Ar is optionally substituted by 1 to 3 substituents A, in which
two of the substituents A can represent a heterocycle fused to the phenyl, such as benzodioxolane, or in which;
each of the substituents A independently represents a group chosen from:
- -OH;
° -CN;
° -Hal;
0 CrC6 -alkyl, optionally substituted by one or more groups chosen from -OH,

-Oalkyl, -CN, -NO2, perfluoroalkyl and-NR2R3, in which
R2 represents H, -alkyl and R3 represents -alkyl, -aryl;

° -alkyl-O-aryl, in which aryl is optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN1 -NO2, -perfluoroalkyl and -NR"2 R"3, in which
R"2 represents H, -alkyl or -NO and R"3 represents -alkyl or -aryl;

° -Oalkyl, optionally substituted by one or more groups chosen from -OH,

-Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

0 -Oalkylaryl, optionally substituted by one or more groups chosen from -OH, -alkyl, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

0 -Oaryl optionally substituted by one or more groups chosen from -OH, - Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR'2RJ3, in which
R'2 represents H or -alkyl and R'3 represents -alkyl, -aryl, -C(=O)alkyl or

-C(=O)aryl;

° -O(alkyl)r-C(=O)-R7, in which r represents 0 or 1 ,
R7 represents an -alkyl, -OR8 or NR9R10 group; in which
R8 represents a hydrogen atom or an -alkyl group;
R9 and R10 independently represent a hydrogen atom or an -alkyl, -alkenyl, -N=alkyl or -N=alkenyl group, in which the alkyl or alkenyl group is optionally substituted by one or more groups chosen from -aryl and -Het, which are themselves optionally substituted by one or more groups chosen from a halogen atom and an -OH1 -alkyl or -Oalkyl group;

° -Oalkyl-O-R11 , in which
R11 represents a group as follows:
-alkyl,
-aryl optionally substituted by one or more groups chosen from -OH, -alkyl and -Oalkyl,
-alkylaryl,
-C(=O)alkyl, optionally substituted by one or more groups chosen from -aryl and -Het;
-C(=O)alkenyl, optionally substituted by -aryl or -Het;
-C(=O)NR12R13, in which R12 and R13 independently represent a hydrogen atom or an -alkyl group;

° -N(NO)-aryl, optionally substituted by one or more groups chosen from -OH, - Oalkyl, -CN, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -NR4R5, in which
R4 represents H or alkyl and R5 represents -alkyl, -aryl or -alkylaryl, in which the -aryl group is optionally substituted by one or more groups chosen from -OH, -alkyl, -Oalkyl, -CN, -NO2, -perfluoroalkyl and -NR'2R'3, in which
R'2 represents H or -alkyl and R'3 represents -alkyl, -aryl, -C(=O)alkyl or -C(=O)aryl;

° -S(O)qR6, in which
q represents 0, 1 or 2,
R6 represents an -alkyl or -aryl group, each optionally substituted by one or more groups chosen from -OH, -Oalkyl, -CN, -NO2-, perfluoroalkyl, -alkyl, -Oalkyl and -NR14R15, in which
R14 and R15 independently represent a hydrogen atom or an -alkyl, -C(=O)alkyl, -C(=O)aryl or -C(=O)Het group, in which, in these last three cases, alkyl, aryl and Het may be optionally substituted by one or more groups chosen from -OH, -CN, -Oalkyl, -NO2, -perfluoroalkyl and -NR2R3, in which
R2 represents H or -alkyl and R3 represents -alkyl or -aryl;

° -perfluoroalkyl;
° -Het;
° -alkylHet;
° -OHet;
or the corresponding salts,
and also the enantiomers, diastereoisomers, racemic mixtures and pharmaceutically acceptable salts,
for the preparation of pharmaceutical compositions for inhibiting oxidative free-radical species and for generating NO.

33. Use of a compound according to Claim 32 for the prevention and/or treatment of pathologies associated with a defect of NO production and/or an increase in tissue oxidative stress.

34. Use according to Claim 33, such that the said pathologies are chosen from atherosclerosis, restenosis, stenosis, hyperglycaemia, insulin resistance, diabetes, dyslipidaemia, retinal and/or renal vascular complications of diabetes, hypoxia, inflammatory processes, cardiovascular diseases, articular pathologies, male erectile dysfunction and smoking.

35. Use according to any one of Claims 28 to 34, for which the compounds of the formula (I) are as defined according to any one of Claims 1 to 11.