Apol1 inhibitors and methods of use

A compound of formula (A):

• or a stereoisomer or a tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
• m is 0 or 1;
• Y is O or —N(C1-6alkyl), wherein the C1-6alkyl of the —N(C1-6alkyl) is optionally substituted with one or more Rg substituents;
• Z1, Z2, Z3, and Z4 are, independently of each other, —N—, —CH— or —C(Rf)—;
• Ra, Rb, and Rc are each independently H, C1-6alkyl, C3-6cycloalkyl, or 3-8 membered heterocycle wherein,
• the C1-6alkyl of Ra, Rb, or Rc is optionally substituted with one or more Rh substituents, and
• the 3-8 membered heterocycle of Ra, Rb, or Rc is optionally substituted with one or more Ri substituents,
• or any two of Ra, Rb, and Rc are taken together with the atoms to which they are attached to form a C3-6cycloalkyl or a 3-8 membered heterocycle, wherein the 3-8 membered heterocycle is optionally substituted with one or more Ri substituents, and the other of Ra, Rb, and Rc is H or C1-6alkyl, C3-6cycloalkyl, or 3-8 membered heterocycle wherein,
• the C1-6alkyl of Ra, Rb, or Rc is optionally substituted with one or more Rh substituents, and
• the 3-8 membered heterocycle of Ra, Rb, or Rc is optionally substituted with one or more R1 substituents;
• Rd and Rare each independently H or C1-6alkyl,
• or Rd and Re are taken together with the atoms to which they are attached to form a C3-6cycloalkyl or a 3-6 membered heterocycle;
• Rf is, independently at each occurrence, —CN, halo, C1-6alkyl, C1-6alkoxy, or —N(Rj)2, wherein the C1-6alkyl of Rf is optionally substituted with one or more halo;
• Rg is, independently at each occurrence, —S(O)2C1-6alkyl;
• Rh is, independently at each occurrence, —OH, C1-6alkoxy, —N(Rj)2, C(O)Rk, or —S(O)2C1-6alkyl;
• Ri is, independently at each occurrence, oxo, C1-6alkyl, or C(O)Rk;
• Rj is independently at each occurrence H, C1-6alkyl or C(O)C1-6alkyl;
• Rk is, independently at each occurrence C1-6alkyl or C1-6alkoxy;
• L is selected from the group consisting of:
• wherein
• Rx and R1 are taken together with the atoms to which they are attached to form a 3-8 membered heterocycle, wherein the 3-8 membered heterocycle is substituted with n independently selected Rm substituents, wherein n is an integer from 0-6, and Rm is C1-6alkyl, or C(O)C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more Rn substituents, and Rn is, independently at each occurrence, —OH;
• R2 is H, —OH, or C1-6alkyl, wherein the C1-6alkyl of R2 is optionally substituted with one or more OH;
• and
• R3 is H or C1-6alkyl, wherein the C1-6alkyl of R3 is optionally substituted with one or more OH;
• provided that when L is (i), either:
• (1) m is 1,
• (2) at least one of Z1, Z2, Z3, and Z4 is —N— or —C(Rf)—,
• (3) R3 is other than H,
• (4) at least one of Ra, Rb, and Rc is heterocycle, or
• (5) at least one of Rg, Ri, Rj, Rk, and Rn is present;
• wherein
• Ry, R4, and R5 are taken together with the atoms to which they are attached to form a 8-20 membered bicyclic heterocycle, wherein the 8-20 membered bicyclic heterocycle is substituted with n independently selected Rm substituents, wherein n is an integer from 0-6, and Rm is C1-6alkyl, or C(O)C1-6alkyl, wherein the C1-6alkyl is optionally substituted with one or more Rn substituents, and Rn is, independently at each occurrence, —OH;
• and
• wherein
• Rz and R6 are taken together with the atoms to which they are attached to form a 3-8 membered heterocycleheterocycle substituted with n independently selected Rm substituents, wherein n is an integer from 0-6, and Rm is C1-6alkyl or C(O)C1-6alkyl, wherein the C1-6 alkyl is optionally substituted with one or more Rn substituents, and Rn is, independently at each occurrence, —OH;
• and
• R7 is taken, together with one of X1 and X2 and the atoms to which they are attached, to form a C4-8cycloalkyl;
• wherein, for each of (i)-(iii), # denotes the point of attachment to the ring bearing moieties moieties Z1-Z4 and ## denotes the point of attachment to the phenyl ring bearing moieties X1-X4;
• X1, and X2 are, independently of each other, H, halo, —CN, C1-6alkyl, C1-6alkoxy, or SF5, wherein the C1-6alkyl or C1-6alkoxy is optionally substituted with one or more halo,
• or one of X1 and X2 is taken together with R7 and the atoms to which it is attached to form a C4-8cycloalkyl, and the other of X1 or X2 is H, halo, —CN, C1-6alkyl, C1-6alkoxy, or SF5, wherein the C1-6alkyl or C1-6alkoxy is optionally substituted with one or more halo;
• and
• X3, and X4 are, independently of each other, H, halo, —CN, C1-6alkyl, C1-6alkoxy, or SF5, wherein the C1-6alkyl or C1-6alkoxy is optionally substituted with one or more halo.