Inhibitors of ngal protein

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:
• X1 represents a nitrogen atom, or a carbon atom;
• X2 represents a carbon atom, or a CH group;
• X3 represents a nitrogen atom;
• X4 represents an oxygen atom, or a carbon atom;
• X5 represents a carbon atom, or a nitrogen atom;
• R5 represents:
• (CH2)n4-N(—C2H5)(—C2H5),
• wherein n4 represents an integer between 0 and 2,
• —CH2—S—R10,
• —S—CH2—R11, or
• —C(═O)—N(H)—R12,
• wherein R10 R11 and R12 each independently represent an heterocycle of general formula (IV)
• wherein
• X6 represents a nitrogen atom, a —NH group, an oxygen atom, or a sulphur atom,
• X7 represents an oxygen atom or a nitrogen atom,
• said heterocycle being optionally substituted by one or more —S(═O)(═O)(—CH2H5), —C(═O)Me, halogeno atoms, trifluoromethyl groups, cyano groups, or nitro groups;
• R6 represents a phenyl group, a lone pair, an oxygen atom, or an halogeno atom;
• R9 represents a ═NH group, or a lone pair;
• R7 and R8 represent a lone pair or R8—X4—X3—R7 optionally form a six membered ring heterocycle, said heterocycle being optionally substituted by one or more methyl groups, preferably by two methyl groups.

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:
• R1 represents:
• (CH2)n1-pyrazole optionally substituted by an aryl group or a pyridinyl group,
• wherein n1 represent an integer between 0 and 1,
• (CH2)n2-aryl, said aryl being optionally substituted by one or more:
• pyrazolyl groups,
• —CH2-pyrazolyl groups,
• thiophenyl groups,
• pyridinyl groups or
• —CH2-piperazinyl groups optionally substituted by one or more ethyl groups,
• phenyl groups optionally substituted by one or more —(CH2)n3-N(—CH3)(—CH3),
• wherein n2 and n3 each independently represent an integer between 0 and 1, or
• —C(═O)—N(H)—R3 wherein R3 represents a cyclohexyl group;
• R2 represents an aryl group optionally substituted by one or more:
• —C(═O)—R4 wherein R4 represents a methyl group;
• —C≡N;
• or
• —NH2;
• or
• ii) the compound of general formula (II):
• wherein:
• X1 represents a nitrogen atom, or a carbon atom;
• X2 represents a carbon atom, or a CH group;
• X3 represents a nitrogen atom;
• X4 represents an oxygen atom, or a carbon atom;
• X5 represents a carbon atom, or a nitrogen atom;
• R5 represents:
• (CH2)n4-N(—C2H5)(—C2H5),
• wherein n4 represents an integer between 0 and 2,
• —CH2—S—R10,
• —S—CH2—R11, or
• —C(═O)—N(H)—R12,
• wherein R10 R11 and R12 each independently represent an heterocycle of general formula (IV)
• wherein
• X6 represents a nitrogen atom, a —NH group, an oxygen atom, or a sulphur atom,
• X7 represents an oxygen atom or a nitrogen atom,
• said heterocycle being optionally substituted by one or more —S(═O)(═O)(—CH2H5), —C(═O)Me, halogeno atoms, trifluoromethyl groups, cyano groups, or nitro groups;
• R6 represents a phenyl group, a lone pair, an oxygen atom, or an halogeno atom;
• R9 represents a ═NH group, or a lone pair;
• R7 and R8 represent a lone pair or R8—X4—X3—R7 optionally form a six membered ring heterocycle, said heterocycle being optionally substituted by one or more methyl groups, preferably by two methyl groups.

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:
• R1 represents:
• (CH2)n1-pyrazole optionally substituted by an aryl group or a pyridinyl group, wherein n1 represent an integer between 0 and 1,
• (CH2)n2-aryl, said aryl being optionally substituted by one or more:
• pyrazolyl groups,
• —CH2-pyrazolyl groups,
• thiophenyl groups,
• pyridinyl groups or
• —CH2-piperazinyl groups optionally substituted by one or more ethyl groups,
• phenyl groups optionally substituted by one or more —(CH2)n3-N(—CH3)(—CH3),
• wherein n2 and n3 each independently represent an integer between 0 and 1, or
• —C(═O)—N(H)—R3 wherein R3 represents a cyclohexyl group;
• R2 represents an aryl group optionally substituted by one or more:
• —C(═O)—R4 wherein R4 represents a methyl group;
• —C≡N;
• or
• —NH2;
• or
• ii) the compound of general formula (II):
• wherein:
• X1 represents a nitrogen atom, or a carbon atom;
• X2 represents a carbon atom, or a CH group;
• X3 represents a nitrogen atom;
• X4 represents an oxygen atom, or a carbon atom;
• X5 represents a carbon atom, or a nitrogen atom;
• R5 represents:
• (CH2)n4-N(—C2H5)(—C2H5),
• wherein n4 represents an integer between 0 and 2,
• —CH2—S—R10,
• —S—CH2—R11, or
• —C(═O)—N(H)—R12,
• wherein R10 R11 and R12 each independently represent an heterocycle of general formula (IV)
• wherein
• X6 represents a nitrogen atom, a —NH group, an oxygen atom, or a sulphur atom,
• X7 represents an oxygen atom or a nitrogen atom,
• said heterocycle being optionally substituted by one or more —S(═O)(═O)(—CH2H5), —C(═O)Me, halogeno atoms, trifluoromethyl groups, cyano groups, or nitro groups;
• R6 represents a phenyl group, a lone pair, an oxygen atom, or an halogeno atom;
• R9 represents a ═NH group, or a lone pair;
• R7 and R8 represent a lone pair or R8—X4—X3—R7 optionally form a six membered ring heterocycle, said heterocycle being optionally substituted by one or more methyl groups, preferably by two methyl groups.