Compounds and methods for treating a cytokine-mediated disease

A compound of the following formula (I):

• wherein:
• A is:
• a hydrogen atom;
• a linear or branched C1-10 alkyl or heteroalkyl group, C2-11 alkenyl, or heteroalkenyl, or a C3-12 cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl group, each of which may be substituted by at least one group selected from the group consisting of:
• a trifluoromethyl, a C1-5 alkyl, alkoxy or alkylamino group, a C2-6 alkenyl, alkenyloxy or alkenylamino group, a C3-12 cycloalkyl or heterocycloalkyl group, a C3-12 aryl, arylamino or heteroaryl group, a halogen atom including F, Cl, Br, and I, a hydroxy group, an amino group, —COOH, —R1COR1′, —R1COOR1′, —R1CONHR1′, —R1NHCOR1′ wherein R1 is selected form the group consisting of a covalent bond, or a C1-5 alkyl, heteroalkyl, alkenyl or heteroalkenyl group, and R1′ is selected from the group consisting of a hydrogen atom, a C1-5 alkyl, heteroalkyl or haloalkyl group, a C2-6 alkenyl, heteroalkenyl or haloalkenyl group, a C3-12 cycloalkyl, heterocycloalkyl, aryl, or heteroaryl group, —NO2, and —SO3H;
• or
• a SO2A′ group wherein A′ is selected from the group consisting of a C1-5 alkyl, heteroalkyl, alkenyl or heteroalkenyl group and a C3-12 cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl group which may be substituted by at least one group selected from the group consisting of:
• a trifluoromethyl, a C1-5 alkyl, alkoxy or alkylamino group, a C2-6 alkenyl, alkenyloxy or alkenylamino group, a C3-12 cycloalkyl or heterocycloalkyl group, a C3-12 aryl, arylamino or heteroaryl group, a halogen atom including F, Cl, Br, and I, a hydroxy group, an amino group, —COOH, —R1COR1′, —R1COOR1′, —R1CONHR1′, —R1NHCOR1′ wherein R1 and R1′ are as defined above;
• B and C, which may be the same or different, independently represent:
• a hydrogen atom;
• or
• a linear or branched C1-10 alkyl or heteroalkyl group, C2-11 alkenyl, or heteroalkenyl, or a C3-12 cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl group, each of which may be substituted by at least one group selected from the group consisting of:
• a trifluoromethyl, a C1-5 alkyl, alkoxy or alkylamino group, a C2-6 alkenyl, alkenyloxy or alkenylamino group, a C3-12 cycloalkyl or heterocycloalkyl group, a C3-12 aryl, arylamino or heteroaryl group, a halogen atom including F, Cl, Br, and I, a hydroxy group, an amino group, —COOH, —R1COR1′, —R1COOR1′, —R1CONHR1′, —R1NHCOR1′ wherein R1 and R1′ are as defined above;
• or
• B and C are joined such that when taken together with the carbon atoms to which they are attached they form a C3-12 cycloalkyl, cycloalkenyl heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl ring which may be substituted by at least one group selected from the group consisting of:
• a trifluoromethyl, a C1-5 alkyl, alkoxy or alkylamino group, a C2-6 alkenyl, alkenyloxy or alkenylamino group, a C3-12 cycloalkyl or heterocycloalkyl group, a C3-12 aryl, arylamino or heteroaryl group, a halogen atom including F, Cl, Br, and I, a hydroxy group, an amino group, a heteroatom selected form N, O or S, —COOH, —R1COR1′, —R1COOR1′, —R1CONHR1′, —R1NHCOR1′ wherein R1 and R1′ are as defined above;
• D is —CH2, —C(O), —NHC(O)—, SO2, or —NHSO2;
• Ra is R2—NR3R4 wherein:
• R2 is a linear or branched C1-5 alkyl or heteroalkyl group, or C2-6 alkenyl, or heteroalkenyl group;
• R3 is:
• a hydrogen atom, or
• a linear of branched C1-5 alkyl or heteroalkyl group, a C2-6 alkenyl or heteroalkenyl group, or a C3-12 cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, cycloalkylalkyl, cycloalkylalkenyl, heterocycloalkylalkyl, heterocycloalkylalkenyl, aryl, heteroaryl, arylalkyl, or heteroarylalkyl group, each of which may be substituted by at least one group selected from the group consisting of a trifluoromethyl, a C1-5 alkyl or alkoxy group, a C2-6 alkenyl group, a halogen atom including F, Cl, Br, and I, a hydroxy group, an amino group, and —COOH;
• R4 is:
• a hydrogen atom;
• a linear or branched C1-10 alkyl or heteroalkyl group, C211 alkenyl, or heteroalkenyl, or a C3-12 cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl group, each of which may be substituted by at least one group selected from the group consisting of:
• a trifluoromethyl, a C1-5 alkyl, alkoxy or alkylamino group, a C2-6 alkenyl, alkenyloxy or alkenylamino group, a C3-12 cycloalkyl or heterocycloalkyl group, a C3-12 aryl, arylamino or heteroaryl group, a halogen atom including F, Cl, Br, and I, a hydroxy group, an amino group, —COOH;
• —SO2NR5R6 or —C(O)NR5R6 wherein R5 and R6, which may be the same or different, independently represent a hydrogen atom, a C1-5 linear of branched alkyl, alkenyl, heteroalkyl or heteroalkenyl, group, or R5 and R6 are joined such that when taken together with the nitrogen atom to which they are attached they form a C3-12 cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl ring;
• —SO2R7, wherein R7 is a hydrogen atom, a C1-5 linear of branched alkyl, alkenyl, heteroalkyl or heteroalkenyl group;
• a C3-12 cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl group which may be substituted by a C1-5 alkyl group, a halogen atom including F, Cl, Br, and I, an amino group, or —NO2;
• or
• —C(O)R7 wherein R7 is as defined above;
• or
• Ra is a compound of the following formula:
• wherein
• R2 is as defined above;
• T, U, V which are the same or different, independently represent —(CH2)n— wherein n is an integer from 1 to 3, or an heteroatom selected from the group consisting of 0, N, and S;
• R8 is:
• a hydrogen atom;
• or
• a linear or branched C1-10 alkyl or heteroalkyl group, C2-11 alkenyl, or heteroalkenyl, or a C3-12 cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl group, each of which may be substituted by at least one group selected from the group consisting of:
• a trifluoromethyl, a C1-5 alkyl, alkoxy or alkylamino group, a C2-6 alkenyl, alkenyloxy or alkenylamino group, a C3-12 cycloalkyl or heterocycloalkyl group, a C3-12 aryl, arylamino or heteroaryl group, a halogen atom including F, Cl, Br, and I, a hydroxy group, an amino group, —COOH or R1COR1′, —R1COOR1′, —R1CONHR1′, —R1NHCOR1′ wherein R1 and R1′ are as defined above;
• Rb is
• wherein
• E, F, G and W which may be the same or different, independently represent —N—, —CH—, —N-oxide, —CNO2, —CN(R1″)4 wherein R1″ is a C1-4 alkyl group, —CF—, —C18F or —C19F;
• or
• wherein
• X1 is selected from a SO2A′ group with A′ as defined above or an aryl or heteroaryl group optionally substituted by at least one group selected from the group consisting of a trifluoromethyl and a C1-5 alkyl group;
• I is —H, —OH, —SH, —CF3, a halogen atom including F, Cl, Br, and I, a linear or branched C1-10 alkyl, heteroalkyl, or haloalkyl group, or C2-11 alkylene, heteroalkylene, or haloalkylene group, or a pharmaceutically acceptable salt or hydrate thereof.