1-(Aromatic- or heteroaromatic-substituted)-3-(heteroaromatic substituted)-1,3-propanediones and uses thereof

A compound of formula:

• 151
• or a tautomer thereof;
• wherein
• A is (i) a benzene ring;
• (ii) an 8- to 10-membered fused bicyclic carbocycle, wherein the ring, of the carbocycle attached to the central dione moiety is a benzene ring, and the other ring of the carbocycle is saturated or unsaturated;
• (iii) an 8 to 10-membered fused bicyclic heterocycle containing carbon atoms and from 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, wherein the ring of the heterocycle attached to the central dione moiety is a benzene ring, and the other ring of the heterocycle is a saturated or unsaturated heteroatom-containing ring;
• or (iv) a 5- or 6-membered heteroaromatic ring containing from 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur;
• and wherein A is attached to the central dione moiety via a carbon atom;
• R1, R2 and R3 are substituents attached to nitrogen or carbon in A;
• R1 is hydrogen, halo, nitro, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, N(Ra)(Rb), (CH2)1-3N(Ra)(Rb), (CH2)0-3Rc, or O(CH2)0-3Rc;
• R2 is hydrogen, halo, nitro, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, N(Ra)(Rb), (CH2)1-3N(Ra)(Rb), (CH2)0-3Rc, O(CH2)0-3Rc, (CH2)0-3Rd, O(H2)0-3Rd, C(═O)CH2C(═O)Re, or Rf;
• R3 is hydrogen, halo, nitro, oxo, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyloxy, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, N(Ra)(Rb), (CH2)1-4N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-4C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-4N(Ra)C(═O)Rb, SO2Ra, (CH2)1-4SO2Ra, SO2N(Ra)(Rb), (CH2)1-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, (CH2)0-3Rc, or (CH2)0-3Rg;
• B is (i) a 5- or 6-membered heteroaromatic ring containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and at least 1 carbon atom, or (ii) an 8- to 10-membered fused bicyclic heterocycle containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and carbon atoms, wherein the ring of the heterocycle attached to the central dione moiety is a 5- or 6-membered heteroaromatic ring containing at least one nitrogen or sulfur atom and the other ring of the heterocycle is a saturated or unsaturated ring;
• wherein B is attached to the central dione moiety via a carbon atom and at least one nitrogen or sulfur atom in B is adjacent to the point of attachment;
• R4 and R5 are substituents attached to nitrogen or carbon in B, and are each independently selected from hydrogen, halo, hydroxy, (CH2)1-4OH, C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkyl, fluorinated C1-C6 alkoxy, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, N(Ra)(Rb), (CH2)1-4N(Ra)(Rb), C(═O)N(Ra)(Rb), (CH2)1-4C(═O)N(Ra)(Rb), N(Ra)C(═O)Rb, (CH2)1-4N(Ra)C(═O)Rb, SO2Ra, (CH2)1-4SO2Ra, SO2N(Ra)(Rb), (CH2)1-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, and(CH2)0-3Rh;
• Ra and Rb are each independently hydrogen, C1-C6 alkyl, or fluorinated C1-C6 alkyl;
• Rc is (i) phenyl or substituted phenyl, wherein each substituent on the substituted phenyl is independently halo, cyano, hydroxy, (CH2)1-4OH, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6-alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl;
• or (ii) an 8- to 10-membered fused bicyclic carbocycle in which one ring is a benzene ring and the other ring is a saturated or unsaturated ring, wherein the fused carbocycle is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl;
• Rd is (i) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains at least one carbon atom and from 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur;
• (ii) an 8- to 10-membered fused bicyclic heterocycle in which either ring is saturated or unsaturated and which contains carbon atoms and from 1 to 4 nitrogen atoms;
• wherein the heterocycle of (i) or (ii) is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, thio, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl;
• or (iii) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains carbon atoms and from 1 to 3 nitrogen atoms, the heterocycle being substituted with spiro-C1-C2 alkylenedioxy or with one of pyrrolidinyl, piperidinyl, piperazinyl, and morpholinyl, unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl;
• Re is a 5- or 6-membered heteroaromatic ring containing from 1 to 4 nitrogen atoms, 0 to 2 sulfur atoms, and at least 1 carbon atom;
• wherein the point of attachment of the ring is a carbon atom and at least one nitrogen or sulfur atom in the ring is adjacent to the point of attachment;
• wherein the ring is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl;
• Rf is X—NH(CH2)1-3Y, wherein X is a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains carbon atoms and from 1 to 3 nitrogen atoms and which is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl;
• Y is pyrrolidinyl, piperidinyl, piperazinyl, or morpholinyl, which is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, and fluorinated C2-C8 alkoxyalkyl;
• Rg is a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains one or more carbon atoms and from 1 to 4 nitrogen atoms, the heterocycle being unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl;
• Rh is (i) C3-C6 cycloalkyl;
• (ii) phenyl;
• (iii) substituted phenyl, wherein each substituent on the substituted phenyl is independently halo, cyano, hydroxy, (CH2)1-4OH, C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, N(Ra)(Rb), (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, or fluorinated C2-C8 alkoxyalkyl, or (iv) a 5- or 6-membered monocyclic heterocycle which is saturated or unsaturated and which contains at least one carbon atom and from 1 to 4 heteroatoms selected from nitrogen, oxygen, and sulfur;
• wherein the heterocycle is unsubstituted or substituted with one or more substituents selected from halo, cyano, hydroxy, (CH2)1-4OH, oxo, N(Ra)(Rb), C1-C6 alkyl, fluorinated C1-C6 alkyl, C1-C6 alkoxy, fluorinated C1-C6 alkoxy, (CH2)0-4CO2Ra, (CH2)0-4C(═O)N(Ra)(Rb), (CH2)0-4SO2Ra, (CH2)1-4N(Ra)(Rb), (CH2)0-4N(Ra)C(═O)Rb, (CH2)0-4SO2N(Ra)(Rb), (CH2)1-4N(Ra)SO2Rb, C2-C8 alkoxyalkyl, fluorinated C2-C8 alkoxyalkyl, phenyl and benzyl;
• or a pharmaceutically acceptable salt thereof.