Substituted pyridinone-containing trycyclic compounds, and methods using same

A compound of formula (IIIa), or a salt, solvate, stereoisomer, geometric isomer, tautomer, or any mixtures thereof:

• wherein:
• R1 is selected from the group consisting of H;
• halo;
• —OR8;
• —C(R9)(R9)OR8;
• —C(═O)R8;
• —C(═O)OR8;
• —C(═O)NH—OR8;
• —C(═O)NHNHR8;
• —C(═O)NHNHC(═O)R8;
• —C(═O)NHS(═O)2R8;
• —CH2C(═O)OR8;
• —CN;
• —NH2;
• —N(R8)C(═O)H;
• —N(R8)C(═O)R10;
• —N(R8)C(═O)OR10;
• —N(R8)C(═O)NHR8;
• —NR9S(═O)2R10;
• —P(═O)(OR8)2;
• —B(OR8)2;
• 2,5-dioxo-pyrrolidin-1-yl;
• 2H-tetrazol-5-yl;
• 3-hydroxy-isoxazol-5-yl;
• 1,4-dihydro-5-oxo-5H-tetrazol-1-yl;
• pyridin-2-yl optionally substituted with C1-C6 alkyl;
• pyrimidin-2-yl optionally substituted with C1-C6 alkyl;
• (pyridin-2-yl)methyl;
• (pyrimidin-2-yl)methyl;
• (pyrimidin-2-yl)amino;
• bis-(pyrimidin-2-yl)-amino;
• 5-R8-1,3,4-thiadiazol-2-yl;
• 5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl;
• 1H-1,2,4-triazol-5-yl;
• 1,3,4-oxadiazol-2-yl;
• 1,2,4-oxadiazol-5-yl, and 3-R10-1,2,4-oxadiazol-5-yl;
• R2 is selected from the group consisting of ═O, ═NR9, =N(OR9), and =N(NR9R9);
• or R1 and R2 combine to form ═N—O—C(═O)— or =N—N(R9)—C(═O)—, wherein the =N group is bound to the ring carbon atom marked “*”;
• X1 is selected from the group consisting of CR6I and N, X2 is selected from the group consisting of CR6II and N, X3 is selected from the group consisting of CR6III and N, X4 is selected from the group consisting of CR6IV and N, or either X3 and X4, or X1 and X2, combine to form —S—;
• wherein 1-2 substituents selected from the group consisting of X1, X2, X3 and X4 are N;
• each of which, if present, is optionally alkylated with C1-C6 alkyl if the adjacent carbon atom in the ring is substituted with —OH;
• R6I, R6II, R6III and R6IV are independently selected from the group consisting of H, halo, —CN, pyrrolidinyl, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkenyl, optionally substituted C3-C8 cycloalkyl, optionally substituted heterocyclyl, —OR, C1-C6 haloalkoxy, —N(R)(R), —NO2, —S(═O)2N(R)(R), acyl, and C1-C6 alkoxycarbonyl,
• wherein each occurrence of R is independently selected from the group consisting of H, C1-C6 alkyl, R′-substituted C1-C6 alkyl, C1-C6 hydroxyalkyl, optionally substituted (C1-C6 alkoxy)-C1-C6 alkyl, and optionally substituted C3-C8 cycloalkyl,
• wherein each occurrence of R′ is independently selected from the group consisting of —NH2, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)(C1-C6 alkyl), —NHC(═O)OtBu, —N(C1-C6 alkyl)C(═O)OtBu, or a 5- or 6-membered heterocyclic group, which is optionally N-linked;
• or X2 is CR6II, X3 is CR6III, and R6II and R6III combine to form a divalent group selected from the group consisting of —O(CHF)O—, —O(CF2)O—, —O(CR9R9)O—, —O(CH2)(CH2)O— and —O(CH2)(CR11R11)(CH2)O—;
• R7 is selected from the group consisting of H, OH, halo, C1-C6 alkoxy, and optionally substituted C1-C6 alkyl;
• R8 is selected from the group consisting of H, optionally substituted C1-C6 alkyl, and optionally substituted C3-C8 cycloalkyl;
• each occurrence of R9 is independently selected from the group consisting of H and C1-C6 alkyl;
• R10 is selected from the group consisting of optionally substituted C1-C6 alkyl and optionally substituted phenyl;
• and,
• each occurrence of R11 is independently selected from the group consisting of H, OH, C1-C6 alkyl, C1-C6 alkoxy, alkoxy-C1-C6 alkyl and alkoxy-C1-C6 alkoxy, wherein two R11 groups bound to the same carbon atom are not simultaneously OH;
• or two R11 groups combine with the carbon atom to which they are bound to form a moiety selected from the group consisting of C═O, C═CH2 and oxetane-3,3-diyl.