| CPC C07D 471/04 (2013.01) [A61K 45/06 (2013.01)] | 26 Claims |
|
1. A compound of Formula (I):
 or a pharmaceutically acceptable salt thereof, wherein:
A is a 5- or 6-membered heteroaryl group which is unsubstituted or substituted with from one to three members independently selected from the group consisting of halogen, C1-3 alkyl, C1-3 haloalkyl, C1-3 alkoxy, OH, and CN;
X1 is a C1-3 alkylene, which is unsubstituted or substituted with one or two members independently selected from the group consisting of C1-2 alkyl and CO2H;
R2a and R2b are each independently selected from the group consisting of H, C1-8 alkyl, C1-8 haloalkyl, —Y, —X2—CO2Ra, —X2—ORa, —X2—NRaRb, —X2—C(O)NRaRb, —X2—SO2Ra, —X2—SO2NRaRb, —X2—SO3Ra, and —X2—Y, wherein each X2 is a C1-6 alkylene, and any C1-8 alkyl or C1-6 alkylene is unsubstituted or substituted with one or two members independently selected from the group consisting of OH, SO2NH2, C(O)NH2, C(O)NHOH, PO3H2, CO2C1-8 alkyl, and CO2H, and each Y is selected from the group consisting of C3-6 cycloalkyl, C4-8 heterocyclyl, and 5- to 6-membered heteroaryl, each of which is unsubstituted or substituted with one to four substituents independently selected from the group consisting of oxo, OH, C1-4 alkyl, C1-4 haloalkyl, C1-4 hydroxyalkyl, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 hydroxyalkoxy, SO2NH2, C(O)NH2, —C(O)NHOH, PO3H2, CO2C1-8alkyl, SO3H, and CO2H;
or R2a and R2b are combined to form a 4- to 9-membered ring or spirocyclic ring, having from zero to two additional heteroatom ring vertices selected from O, N and S;
wherein the 4- to 9-membered ring or spirocyclic ring formed by combining R2a and R2b is unsubstituted or substituted with 1 to 4 substituents independently selected from the group consisting of oxo, C1-8 alkyl, C1-8 haloalkyl, C1-8 hydroxyalkyl, —X3—CO2Ra, —X3—ORa, —X3—NRaRb, —X3—C(O)NRaRb, —X3—SO2Ra, —X3—SO2NRaRb, and —X3—SO3Ra, wherein X3 is a bond or C1-6 alkylene;
R3 and R4 are each independently selected from the group consisting of H, F, Cl, CN, CH3, OCH3, CH2CH3, and CF3;
the subscript n is 0, 1, 2, or 3;
each R3a is independently selected from the group consisting of H, F, Cl, C1-3 alkyl, C1-3 alkoxy, C1-3 haloalkyl, C1-3 haloalkoxy, C2-3 alkenyl, and CN;
R6, R7, and R8 are each independently selected from the group consisting of H, F, Cl, CN, CH3, OCH3, CH2CH3, and CF3;
Z is selected from the group consisting of
  unsubstituted or substituted with one to three Rc;
each Ra is independently selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkylene-CO2H, and C1-6 alkylene-SO3H;
each Rb is independently selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 alkylene-CO2H, and C1-6 alkylene-SO3H, each of which is unsubstituted or substituted with one or two members independently selected from OH, SO2NH2, C(O)NH2, C(O)NHOH, PO3H2, CO2C1-8 alkyl, and CO2H;
and Ra and Rb, when attached to the same nitrogen atom, are optionally combined to form a 4- to 8-membered ring or spirocyclic ring, which is unsubstituted or substituted with halogen, OH, SO2NH2, C(O)NH2, C(O)NHOH, PO3H2, CO2C1-8 alkyl, or —CO2H; and
each Rc is independently selected from the group consisting of H, halogen, CN, C1-6 alkyl, C1-6 haloalkyl, —Y1, —X4—CO2Ra, —O—X4—CO2Ra, —X4—ORa, —X4—NRaRb, —X4—C(O)NRaRb, —O—X4—C(O)NRaRb, —X4—SO2Ra, —X4—SO2NRaRb, —X4—SO3Ra, and —N(Ra)—X4—CO2Ra, wherein each X4 is a bond or C1-6 alkylene, and each Y1 is independently selected from the group consisting of C3-6 cycloalkyl and C4-8 heterocyclyl; and optionally two Rc on adjacent ring vertices are combined to form a fused 5- or 6-membered heterocyclic ring.
|