Substituted 1,1'-biphenyl compounds and methods using same

A compound, or a salt, solvate, geometric isomer, stereoisomer, or tautomer thereof, selected from the group consisting of:

• (a) a compound of formula (Ib):
• wherein:
• R1a is selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R1b is selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R1c is selected from the group consisting of:
• R1d is selected from the group consisting of:
• R′1, R′2, and R′3 are independently selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R″1, R″2, and R″3 are independently selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• each occurrence of X4 is independently selected from the group consisting of CRX4 and N, wherein each occurrence of RX4 is selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R3a is selected from the group consisting of —CHO, —C(O)ORIII, —C(═O)NRIIIRIII, —C(═NRS)NRIIIRIII, optionally substituted heterocyclyl, —(CH2)1-3(optionally substituted heterocyclyl), optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 aminoalkyl, and optionally substituted C1-C6 hydroxyalkyl,
• wherein each occurrence of RIII is independently H, C1-C6 alkyl, or C3-C8 cycloalkyl, wherein the alkyl or cycloalkyl is independently optionally substituted with at least one of halogen, —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), and —N(C1-C6 alkyl)(C1-C6 alkyl),
• or two RIII can combine with the N atom to which they are bound to form 3-membered to 8-membered optionally substituted heterocyclyl,
• or, if R3a is —C(═NR5)NRIIIRIII, then R5 and one Rm can combine to form 4-membered to 8-membered optionally substituted heterocyclyl,
• or, if X3 is CRX3 and R3a has a tetravalent a carbon, then optionally RX3 and the tetravalent a carbon of R3a combine to form a 3-membered to to 8-membered carbocyclyl;
• each occurrence of R3b is independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 aminoalkyl, optionally substituted C1-C6 hydroxyalkyl, optionally substituted C3-C8 cycloalkyl, —CHO, —C(O)ORIV, —C(═O)NRIVRIV, —C(═NR5)NRIVRIV, —NR3d(optionally substituted alkyl), optionally substituted heterocyclyl, and —(CH2)1-3(optionally substituted heterocyclyl),
• wherein each occurrence of RIV is independently H, C1-C6 alkyl, or C3-C8 cycloalkyl, wherein the alkyl or cycloalkyl is independently optionally substituted with at least one of halogen, —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), and —N(C1-C6 alkyl)(C1-C6 alkyl),
• or two RIV can combine with the N atom to which they are bound to form 3-membered to 8-membered optionally substituted heterocyclyl,
• or, if R3b is —C(═NR5)NRIVRIV, then R5 and one RIV can combine to form 4-membered to 8-membered optionally substituted heterocyclyl;
• each occurrence of R3, is independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, and optionally substituted C1-C6 acyl;
• each occurrence of R3d is independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, and optionally substituted C1-C6 acyl;
• each occurrence of R5 is independently H, C1-C6 alkyl, or C3-C8 cycloalkyl, wherein the alkyl or cycloalkyl is independently optionally substituted with at least one of halogen, —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), and —N(C1-C6 alkyl)(C1-C6 alkyl),
• each occurrence of RV1, RV2, RV3, RV4, RV5, RV6, RV7, RV8, RV9, RV10, and RV11 is independently selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• (b) a compound of formula (Ia):
• wherein:
• X1 is selected from the group consisting of CRX1 and N, wherein each occurrence of RX1 is independently selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• X2 is selected from the group consisting of bond, —OCH2—**, —CH2O—**, —CH═CH—**, —CF═CH—**, —CH═CF—**, —CF═CF—**, —C(═O)NH—**, and —NHC(═O)—**,
• wherein the bond marked with ** is to the phenyl ring carbon marked with *;
• X3 is selected from the group consisting of CRX3 and N, wherein each occurrence of RX3 is independently selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R′1, R′2, and R′3 are independently selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R″11, R″2, and R″3 are independently selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R1a is selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R1b is selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R1c is selected from the group consisting of:
• each occurrence of X4 is independently selected from the group consisting of CRX4 and N, wherein each occurrence of RX4 is independently selected from the group consisting of H, C1-C3 alkyl, C3-C5 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• R2a is selected from the group consisting of H, halogen, optionally substituted C1-C6 alkyl, optionally substituted C3-C5 cycloalkyl, —(CH2)1-3(optionally substituted phenyl), —(CH2)1-3(optionally substituted heteroaryl), —OR, —SR1, —NRIRI, —O(CH2)1-3(optionally substituted phenyl), —O(CH2)1-3(optionally substituted heteroaryl), —(CH2)1-3C(═O)OR, —(CH2)1-3C(═O)NR′R′, —O(CH2)1-3C(═O)OR′, and —O(CH2)1-3C(═O)NRIIIRIII,
• wherein each occurrence of R is independently H, C1-C6 alkyl, or C3-C8 cycloalkyl, wherein the alkyl or cycloalkyl is independently optionally substituted with at least one of halogen, —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), and —N(C1-C6 alkyl)(C1-C6 alkyl),
• or two R can combine with the N atom to which they are bound to form 3-membered to 8-membered optionally substituted heterocyclyl;
• R3a is selected from the group consisting of —CHO, —C(O)ORIII, —C(═O)NRIIIRIII, —C(═NR5)NRIIIRIII, optionally substituted heterocyclyl, —(CH2)1-3(optionally substituted heterocyclyl), optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 aminoalkyl, and optionally substituted C1-C6 hydroxyalkyl,
• wherein each occurrence of RIII is independently H, C1-C6 alkyl, or C3-C8 cycloalkyl, wherein the alkyl or cycloalkyl is independently optionally substituted with at least one of halogen, —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), and —N(C1-C6 alkyl)(C1-C6 alkyl),
• or two RIII can combine with the N atom to which they are bound to form 3-membered to 8-membered optionally substituted heterocyclyl,
• or, if R3a is —C(═NR5)NRIIIRIII, then R5 and one RIII can combine to form 4-membered to 8-membered optionally substituted heterocyclyl,
• or, if X3 is CRX3 and R3a has a tetravalent a carbon, then optionally RX3 and the tetravalent a carbon of R3a combine to form a 3-membered to to 8-membered carbocyclyl;
• R3b is selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 aminoalkyl, optionally substituted C1-C6 hydroxyalkyl, optionally substituted C3-C8 cycloalkyl, —CHO, —C(O)OR1V, —C(═O)NRIVRIV, —C(═NR5)NR1VR1V, —NR3′ (optionally substituted alkyl), optionally substituted heterocyclyl, and —(CH2)1-3(optionally substituted heterocyclyl),
• wherein each occurrence of RIV is independently H, C1-C6 alkyl, or C3-C8 cycloalkyl, wherein the alkyl or cycloalkyl is independently optionally substituted with at least one of halogen, —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), and —N(C1-C6 alkyl)(C1-C6 alkyl),
• or two R1V can combine with the N atom to which they are bound to form 3-membered to 8-membered optionally substituted heterocyclyl,
• or, if R3b is —C(═NR5)NRIVR1V, then R5 and one R1V can combine to form 4-membered to 8-membered optionally substituted heterocyclyl;
• each occurrence of R3c is independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, and optionally substituted C1-C6 acyl;
• each occurrence of R3d is independently selected from the group consisting of H, optionally substituted C1-C6 alkyl, optionally substituted C3-C8 cycloalkyl, and optionally substituted C1-C6 acyl;
• R4a is selected from the group consisting of H, halogen, cyano, C1-C3 alkyl, and C3-C8 cycloalkyl;
• each occurrence of R5 is independently H, C1-C6 alkyl, or C3-C8 cycloalkyl, wherein the alkyl or cycloalkyl is independently optionally substituted with at least one of halogen, —OH, C1-C6 alkoxy, —NH2, —NH(C1-C6 alkyl), and —N(C1-C6 alkyl)(C1-C6 alkyl),
• each occurrence of RV1, RV2, RV3, RV4, RV5, RV6, RV7, RV8, RV9, RV10, and RV11 is independently selected from the group consisting of H, C1-C3 alkyl, C3-C8 cycloalkyl, C1-C3 alkoxy, cyano, halogen, C1-C3 haloalkyl, and C1-C3 haloalkoxy;
• and any mixtures thereof.