INHIBITORS OF NGAL PROTEIN

1 . A method of inhibiting NGAL in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of general formula (I):

wherein:

R 1 represents:

(CH 2 ) n1 -pyrazole optionally substituted by an aryl group or a pyridinyl group,

wherein n 1 represent an integer between 0 and 1,

(CH 2 ) n2 -aryl, said aryl being optionally substituted by one or more:

pyrazolyl groups,

—CH 2 -pyrazolyl groups,

thiophenyl groups,

pyridinyl groups or

—CH 2 -piperazinyl groups optionally substituted by one or more ethyl groups,

phenyl groups optionally substituted by one or more —(CH 2 )n 3 -N(—CH 3 )(—CH 3 ),

wherein n 2 and n 3 each independently represent an integer between 0 and 1, or

—C(═O)—N(H)—R 3 wherein R 3 represents a cyclohexyl group;

R 2 represents an aryl group optionally substituted by one or more:

—C(═O)—R 4 wherein R 4 represents a methyl group;

—C≡N; or

—NH 2 .

2 . The method according to claim 1 , wherein:

R 1 represents:

(CH 2 ) n2 -aryl, said aryl being optionally substituted by one or more:

pyrazolyl groups,

—CH 2 -pyrazolyl groups,

thiophenyl groups,

pyridinyl groups, or

—CH 2 -piperazinyl groups optionally substituted by one or more ethyl groups,

phenyl groups optionally substituted by one or more —(CH 2 )n 3 -N(—CH 3 )(—CH 3 ),

wherein n 2 and n 3 each independently represent an integer between 0 and 1;

R 2 represents an aryl group optionally substituted by one or more:

—C(═O)—R 4 wherein R 4 represents a methyl group; or

—C≡N.

3 . A method of inhibiting NGAL in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of general formula (II):

wherein:

X 1 represents a nitrogen atom, or a carbon atom;

X 2 represents a carbon atom, or a CH group;

X 3 represents a nitrogen atom;

X 4 represents an oxygen atom, or a carbon atom;

X 5 represents a carbon atom, or a nitrogen atom;

R 5 represents:

(CH 2 )n 4 -N(—C 2 H 5 )(—C 2 H 5 ),

wherein n 4 represents an integer between 0 and 2,

—CH 2 —S—R 10 ,

—S—CH 2 —R 11 , or

—C(═O)—N(H)—R 12 ,

wherein R 10 R 11 and R 12 each independently represent an heterocycle of general formula (IV)

wherein

 X 6 represents a nitrogen atom, a —NH group, an oxygen atom, or a sulphur atom,

 X 7 represents an oxygen atom or a nitrogen atom,

said heterocycle being optionally substituted by one or more —S(═O)(═O)(—CH 2 H 5 ), —C(═O)Me, halogeno atoms, trifluoromethyl groups, cyano groups, or nitro groups;

R 6 represents a phenyl group, a lone pair, an oxygen atom, or an halogeno atom;

R 9 represents a ═NH group, or a lone pair;

R 7 and R 8 represent a lone pair or R 8 —X 4 —X 3 —R 7 optionally form a six membered ring heterocycle, said heterocycle being optionally substituted by one or more methyl groups, preferably by two methyl groups.

4 . The method according to claim 3 , wherein the compound is a compound of general formula (III):

wherein

R 13 represents

—CH 2 —S—R 17 ,

—S—CH 2 —R 18 , or

—C(═O)—N(H)—R 19 ,

wherein R 17 , R 18 and R 19 each independently represent an heterocycle of general formula (V)

wherein

X 8 represents a nitrogen atom, a —NH group, an oxygen atom, or a sulphur atom,

X 9 represents an oxygen atom or a nitrogen atom,

said heterocycle being optionally substituted by one or more —S(═O)(═O) (—CH 2 H 5 ), halogeno atoms or nitro groups;

R 14 represents a lone pair, a hydrogen atom or an halogen atom;

R 15 represents a methyl group, a hydrogen atom or a lone pair; and

R 16 represents a methyl group, a hydrogen atom or a lone pair.

5 - 8 . (canceled)

9 . A method of treating a wound and/or delayed wound closure in a subject in need thereof, comprising

administering to the subject a therapeutically effective amount of

i) the compound of general formula (I):

wherein:

R 1 represents:

(CH 2 ) n1 -pyrazole optionally substituted by an aryl group or a pyridinyl group,

wherein n 1 represent an integer between 0 and 1,

(CH 2 ) n2 -aryl, said aryl being optionally substituted by one or more:

pyrazolyl groups,

—CH 2 -pyrazolyl groups,

thiophenyl groups,

pyridinyl groups or

—CH 2 -piperazinyl groups optionally substituted by one or more ethyl groups,

phenyl groups optionally substituted by one or more —(CH 2 )n 3 -N(—CH 3 )(—CH 3 ),

wherein n 2 and n 3 each independently represent an integer between 0 and 1, or

—C(═O)—N(H)—R 3 wherein R 3 represents a cyclohexyl group;

R 2 represents an aryl group optionally substituted by one or more:

—C(═O)—R 4 wherein R 4 represents a methyl group;

—C≡N; or

—NH 2 ;

or

ii) the compound of general formula (II):

wherein:

X 1 represents a nitrogen atom, or a carbon atom;

X 2 represents a carbon atom, or a CH group;

X 3 represents a nitrogen atom;

X 4 represents an oxygen atom, or a carbon atom;

X 5 represents a carbon atom, or a nitrogen atom;

R 5 represents:

(CH 2 )n 4 -N(—C 2 H 5 )(—C 2 H 5 ),

wherein n 4 represents an integer between 0 and 2,

—CH 2 —S—R 10 ,

—S—CH 2 —R 11 , or

—C(═O)—N(H)—R 12 ,

wherein R 10 R 11 and R 12 each independently represent an heterocycle of general formula (IV)

wherein

X 6 represents a nitrogen atom, a —NH group, an oxygen atom, or a sulphur atom,

X 7 represents an oxygen atom or a nitrogen atom,

said heterocycle being optionally substituted by one or more —S(═O)(═O)(—CH 2 H 5 ), —C(═O)Me, halogeno atoms, trifluoromethyl groups, cyano groups, or nitro groups;

R 6 represents a phenyl group, a lone pair, an oxygen atom, or an halogeno atom;

R 9 represents a ═NH group, or a lone pair;

R 7 and R 8 represent a lone pair or R 8 —X 4 —X 3 —R 7 optionally form a six membered ring heterocycle, said heterocycle being optionally substituted by one or more methyl groups, preferably by two methyl groups.

10 . A method for treating an NGAL induced disease in a patient in need thereof comprising, administering to the patient a therapeutically effective amount of

i) the compound of general formula (I):

wherein:

R 1 represents:

(CH 2 ) n1 -pyrazole optionally substituted by an aryl group or a pyridinyl group, wherein n 1 represent an integer between 0 and 1,

(CH 2 ) n2 -aryl, said aryl being optionally substituted by one or more:

pyrazolyl groups,

—CH 2 -pyrazolyl groups,

thiophenyl groups,

pyridinyl groups or

—CH 2 -piperazinyl groups optionally substituted by one or more ethyl groups,

phenyl groups optionally substituted by one or more —(CH 2 )n 3 -N(—CH 3 )(—CH 3 ),

wherein n 2 and n 3 each independently represent an integer between 0 and 1, or

—C(═O)—N(H)—R 3 wherein R 3 represents a cyclohexyl group;

R 2 represents an aryl group optionally substituted by one or more:

—C(═O)—R 4 wherein R 4 represents a methyl group;

—C≡N; or

—NH 2 ;

or

ii) the compound of general formula (II):

wherein:

X 1 represents a nitrogen atom, or a carbon atom;

X 2 represents a carbon atom, or a CH group;

X 3 represents a nitrogen atom;

X 4 represents an oxygen atom, or a carbon atom;

X 5 represents a carbon atom, or a nitrogen atom;

R 5 represents:

(CH 2 )n 4 -N(—C 2 H 5 )(—C 2 H 5 ),

wherein n 4 represents an integer between 0 and 2,

—CH 2 —S—R 10 ,

—S—CH 2 —R 11 , or

—C(═O)—N(H)—R 12 ,

wherein R 10 R 11 and R 12 each independently represent an heterocycle of general formula (IV)

wherein

X 6 represents a nitrogen atom, a —NH group, an oxygen atom, or a sulphur atom,

X 7 represents an oxygen atom or a nitrogen atom,

said heterocycle being optionally substituted by one or more —S(═O)(═O)(—CH 2 H 5 ), —C(═O)Me, halogeno atoms, trifluoromethyl groups, cyano groups, or nitro groups;

R 6 represents a phenyl group, a lone pair, an oxygen atom, or an halogeno atom;

R 9 represents a ═NH group, or a lone pair;

R 7 and R 8 represent a lone pair or R 8 —X 4 —X 3 —R 7 optionally form a six membered ring heterocycle, said heterocycle being optionally substituted by one or more methyl groups, preferably by two methyl groups.

11 . The method of claim 9 , wherein the wound is a chronic wound.