Small molecule inhibitors of interferon gamma signaling

A compound of the following general formula (I):

• or a pharmaceutically acceptable salt, stereoisomer, tautomer or solvate thereof,
• wherein,
• X is an oxygen or sulfur atom;
• R1 is a chlorine atom or a (C2-C6)alkynyl group;
• R2 and R3 are, independently of one another, a hydrogen atom, a (C0-C6)alkyl-ethynyl (—(CH2)0-6—C≡CH);
• a (C0-C3)alkyl-NH—C(O)—R′;
• a (C0-C3)alkyl-C(O)—NR′R″;
• a (C0-C3)alkyl-NH—C(O)—OR′;
• a (C0-C3)alkyl-NH—C(O)—NR′R″;
• a (C0-C3)alkyl-C(O)—R′;
• a (C0-C3)alkyl-C(O)—OR′;
• a (C0-C3)alkyl-NR′R″;
• a (C0-C3)alkyl-SOR′;
• a (C0-C3)alkyl-SO2R′;
• a (C0-C3)alkyl-SONR′R″;
• a (C0-C3)alkyl-SO2NR′R″;
• (C0-C3)alkyl-NHSO2R′;
• or a group selected from (C1-C6)alkyl group, (C1-C6)alkyloxy group, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C10)cycloalkyl group, (C3-C10)heterocycloalkyl group, (C6-C12)aryl group, or (C5-C12)heteroaryl group;
• said group being optionally substituted by at least one R;
• R is independently selected from the group consisting of a halo, a hydroxyl, a thiol, a cyano, a nitro, an amino (—NH2), a phosphate (PO43−), —CF3, a (C1-C6)alkyl group, a (C2-C6)alkenyl, a (C2-C6)alkynyl, or a (C1-C6)alkyloxy group;
• and
• R′ and R″ are independently selected from the group consisting of a hydrogen atom or a (C1-C6)alkyl group optionally substituted by at least one halogen;
• provided that said compound is not a compound (Ia) or (Ib):

A method of inhibiting formin FH2 domains in a cell comprising contacting a cell with a compound selected from the group consisting of:

• Compound 5l
• 1-(3-bromophenyl)-5-((5-
• ethynylfuran-2-
• yl)methylene)pyrimidine-
• 2,4,6(1H,3H,5H)-trione
• Compound 6a
• 1-(3-fluorophenyl)-5-((5-
• methylfuran-2-yl)methylene)-2-
• thioxodihydropyrimidine-
• 4,6(1H,5H)-dione
• Compound 6i
• 5-((5-bromofuran-2-
• yl)methylene)-1-(3-
• fluorophenyl)-2-
• thioxodihydropyrimidine-
• 4,6(1H,5H)-dione
• Compound 6j
• 1,3-bis(3-fluorophenyl)-5-((5-
• methylfuran-2-yl)methylene)-2-
• thioxodihydropyrimidine-
• 4,6(1H,5H)-dione
• Compound 6k
• 5-(furan-2-ylmethylene)-1-
• phenyl-2-
• thioxodihydropyrimidine-
• 4,6(1H,5H)-dione
• Compound 6l
• 1-(3-bromophenyl)-5-(furan-2-
• ylmethylene)pyrimidine-
• 2,,6(1H,3H,5H)-trione
• Compound 6m
• 1-(3-fluorophenyl)-5-(furan-2-
• ylmethylene)-2-
• thioxodihydropyrimidine-
• 4,6(1H,5H)-dione

A method for inhibiting interferon-γ mediated signaling in a subject in need thereof, comprising administering a therapeutically effective amount of a compound of general formula (I) or a pharmaceutical composition comprising said compound to said subject, wherein said compound has general formula (I):

• or is a pharmaceutically acceptable salt, stereoisomer, tautomer or solvate thereof,
• wherein,
• X is an oxygen or sulfur atom;
• R1 is a hydrogen atom, halo, nitro (NO2), (C1-C6)alkyl group or (C2-C6)alkynyl group;
• R2 and R3 are, independently of one another, a hydrogen atom, a (C0-C6)alkyl-ethynyl (—(CH2)0-6—C≡CH);
• a (C0-C3)alkyl-NH—C(O)—R′;
• a (C0-C3)alkyl-C(O)—NR′R″;
• a (C0-C3)alkyl-NH—C(O)—OR′;
• a (C0-C3)alkyl-NH—C(O)—NR′R″;
• a (C0-C3)alkyl-C(O)—R′;
• a (C0-C3)alkyl-C(O)—OR′;
• a (C0-C3)alkyl-NR′R″;
• a (C0-C3)alkyl-SOR′;
• a (C0-C3)alkyl-SO2R′;
• a (C0-C3)alkyl-SONR′R″;
• a (C0-C3)alkyl-SO2NR′R″;
• (C0-C3)alkyl-NHSO2R′;
• or a group selected from (C1-C6)alkyl group, (C1-C6)alkyloxy group, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C10)cycloalkyl group, (C3-C10)heterocycloalkyl group, (C6-C12)aryl group, or (C5-C12)heteroaryl group;
• said group being optionally substituted by at least one R;
• R is independently selected from the group consisting of a halo, a hydroxyl, a thiol, a cyano, a nitro, an amino (—NH2), a phosphate (PO43−), —CF3, a (C1-C6)alkyl group, a (C2-C6)alkenyl, a (C2-C6)alkynyl, or a (C1-C6)alkyloxy group;
• and
• R′ and R″ are independently selected from the group consisting of a hydrogen atom or a (C1-C6)alkyl group optionally substituted by at least one halogen.