Dimer of biguanidines and their therapeutic uses

A method of treating an inflammatory disease or disorder or an autoimmune disease or disorder comprising administering a compound of formula (I) to a subject having said inflammatory or autoimmune disease or disorder,

• wherein the formula (I) is
• with
• R1, R2, R3, R4, R5, R6, R7 and R8 being independently selected from the group consisting of H, a C1-C6alkyl, a C0-C6alkyl-ethynyl (—(CH2)0-6—C≡CH), a C3-C10cycloalkyl, a C3-C10cycloheteroalkyl, a C6-C12aryl, and a C5-C12heteroaryl, said alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl being optionally substituted by a R group or a R′ group;
• or
• R2, R3, R4, R5, R6, and R7 being independently selected from the group consisting of H, a C1-C6alkyl, a C0-C6alkyl-ethynyl (—(CH2)0-6—C≡CH), a C3-C10cycloalkyl, a C3-C10cycloheteroalkyl, a C6-C12aryl, and a C5-C12heteroaryl, said alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl being optionally substituted by a R group or a R′ group, and R1 and R8 forming together a linker -L′-,
• -L- and -L′-, if present, being independently a linear hydrocarbon chain of 8 to 16 carbons optionally interrupted by
• an oxygen atom;
• and/or
• a function selected from the group consisting of amide (—C(O)—NH— or —NH—C(O)—), carbonyl (—C(O)—), ester (—C(O)—O— or —O—C(O)—), sulfonyl (—SO2—), sulfinyl (—S(O)—), thiocarbonyl (—C(S)—), thioester (—C(O)—S— or —S—C(O)—), carbonyloxy (—O—C(O)—O—), —S(O)—NH—, —NH—S(O)—, —SO2—NH—, —NH—SO2—, phosphate (—O—P(O)OH—O—) and phosphonate (—P(O)OH—O— or —O—P(O)OH—);
• and/or
• a 3-7-membered ring, optionally selected from the group consisting of a cycloalkyl, a heterocycloalkyl, an aryl, and a heteroaryl, said ring being optionally substituted by a group R or R′;
• said linear hydrocarbon chain being optionally substituted by a group R or R′;
• with R being selected from the group consisting of a C1-C6alkyl optionally substituted by at least one halogen, a C1-C6alkyloxy optionally substituted by at least one halogen, a C3-C10cycloalkyl, a C3-C10cycloheteroalkyl, a C6-C12aryl, and a C5-C12heteroaryl, the group being optionally substituted by a group R′, and
• R′ being selected from the group consisting of a halogen, a hydroxyl, a thiol, a cyano, an ethynyl (—C≡CH), a nitro, an amino (—NH2), a phosphate (PO43-), a C1-C6alkyl optionally substituted by at least one halogen, a C1-C6alkoxy optionally substituted by at least one halogen, a C1-C6thioalkyl optionally substituted by at least one halogen, C0-C3alkyl-NH—C(O)—R″, C0-C3alkyl-C(O)—NR″R″, C0-C3alkyl-NH—C(O)—OR″, C0-C3alkyl-NH—C(O)—NR″R″, C0-C3alkyl-C(O)—R″, C0-C3alkyl-C(O)—OR″, C0-C3alkyl-NR″R″, C0-C3alkyl-SOR″, C0-C3alkyl-SO2R″, C0-C3alkyl-SONR″R″, C0-C3alkyl-SO2NR″R″, C0-C3alkyl-NHSO2R″, -a C3-C10cycloalkyl, a C3-C10cycloheteroalkyl, a C6-C12aryl, and a C5-C12heteroaryl, with R″ being H or a C1-C3 or C1-C6alkyl optionally substituted by at least one halogen and said cycloalkyl, cycloheteroalkyl, aryl or heteroaryl being optionally substituted by a halogen, a hydroxyl, a cyano, a nitro, an amino, or a C1-C3alkoxy,
• or a pharmaceutically acceptable salt, stereoisomer, tautomer or solvate thereof.

A compound of formula (I) wherein the formula (I) is

• wherein
• R2, R3, R4, R5, R6, and R7 being independently selected from the group consisting of H, a C1-C6alkyl, a C0-C6alkyl-ethynyl (—(CH2)0-6—C≡CH), a C3-C10cycloalkyl, a C3-C10cycloheteroalkyl, a C6-C12aryl, and a C5-C12heteroaryl, said alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl being optionally substituted by a R group or a R′ group;
• and
• 1) R1 and R8 being independently selected from the group consisting of H, a C1-C6alkyl, a C0-C6alkyl-ethynyl (—(CH2)0-6—C≡CH), a C3-C10cycloalkyl, a C3-C10cycloheteroalkyl, a C6-C12aryl, and a C5-C12heteroaryl, said alkyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl being optionally substituted by a R group or a R′ group;
• and
• -L- being independently a linear hydrocarbon chain of 11 to 16 carbons optionally interrupted by
• an oxygen atom;
• and/or
• a function selected from the group consisting of amide (—C(O)—NH— or —NH—C(O)—), carbonyl (—C(O)—), ester (—C(O)—O— or —O—C(O)—), sulfonyl (—SO2—), sulfinyl (—S(O)—), thiocarbonyl (—C(S)—), thioester (—C(O)—S— or —S—C(O)—), carbonyloxy (—O—C(O)—O—), —S(O)—NH—, —NH—S(O)—, —SO2—NH—, —NH—SO2—, phosphate (—O—P(O)OH—O—) and phosphonate (—P(O)OH—O— or —O—P(O)OH—);
• and/or
• a 3-7-membered ring, optionally selected from the group consisting of a cycloalkyl, a heterocycloalkyl, an aryl, and a heteroaryl, said ring being optionally substituted by a group R or R′;
• said linear hydrocarbon chain being optionally substituted by a group R or R′;
• or
• 2) R1 and R8 forming together a linker -L′-;
• and
• -L- and -L′- being independently a linear hydrocarbon chain of 4 to 16 carbons optionally interrupted by
• a heteroatom;
• and/or
• a function selected from the group consisting of amide (—C(O)—NH— or —NH—C(O)—), carbonyl (—C(O)—), ester (—C(O)—O— or —O—C(O)—), sulfonyl (—SO2—), sulfinyl (—S(O)—), thiocarbonyl (—C(S)—), thioester (—C(O)—S— or —S—C(O)—), carbonyloxy (—O—C(O)—O—), —S(O)—NH—, —NH—S(O)—, —SO2—NH—, —NH—SO2—, phosphate (—O—P(O)OH—O—) and phosphonate (—P(O)OH—O— or —O—P(O)OH—);
• and/or
• a 3-7-membered ring, optionally selected from the group consisting of a cycloalkyl, a heterocycloalkyl, an aryl, and a heteroaryl, said ring being optionally substituted by a group R or R′;
• said linear hydrocarbon chain being optionally substituted by a group R or R′;
• or
• 3) the compound is selected from the group consisting of
• with n being an integer from 2-14 or from 4-14 or from 8-14 or from 8-12 or from 8-10;
• and
• with n being an integer from 6-16, from 8-16 or from 8-12 or from 8-10 and R being an ethyl, a propyl or —CH2—C≡CH,
• wherein in item 1) and 2)
• R being selected from the group consisting of a C1-C6alkyl optionally substituted by at least one halogen, a C1-C6alkyloxy optionally substituted by at least one halogen, a C3-C10cycloalkyl, a C3-C10cycloheteroalkyl, a C6-C12aryl, and a C5-C12heteroaryl, the group being optionally substituted by a group R′, and
• R′ being selected from the group consisting of a halogen, a hydroxyl, a thiol, a cyano, an ethynyl (—C≡CH), a nitro, an amino (—NH2), a phosphate (PO43-), a C1-C6alkyl optionally substituted by at least one halogen, a C1-C6alkoxy optionally substituted by at least one halogen, a C1-C6thioalkyl optionally substituted by at least one halogen, C0-C3alkyl-NH—C(O)—R″, C0-C3alkyl-C(O)—NR″R″, C0-C3alkyl-NH—C(O)—OR″, C0-C3alkyl-NH—C(O)—NR″R″, C0-C3alkyl-C(O)—R″, C0-C3alkyl-C(O)—OR″, C0-C3alkyl-NR″R″, C0-C3alkyl-SOR″, C0-C3alkyl-SO2R″, C0-C3alkyl-SONR″R″, C0-C3alkyl-SO2NR″R″, C0-C3alkyl-NHSO2R″, -a C3-C10cycloalkyl, a C3-C10cycloheteroalkyl, a C6-C12aryl, and a C5-C12heteroaryl, with R″ being H or a C1-C3 or C1-C6alkyl optionally substituted by at least one halogen and said cycloalkyl, cycloheteroalkyl, aryl or heteroaryl being optionally substituted by a halogen, a hydroxyl, a cyano, a nitro, an amino, or a C1-C3alkoxy,
• or a pharmaceutically acceptable salt, stereoisomer, tautomer or solvate of any of these compounds.