Oxoacridinyl acetic acid derivatives and methods of use

A compound of Formula I:

• or a pharmaceutically acceptable salt or ester thereof, wherein
• X is C(RX)2, O, S, CH═CH, or absent;
• each RX is independently H, CH3, CF3, CF2H, or F, or two RX together form ═O, ═CH2, or ═CF2, or two RX, together with the carbon atom to which they are bonded, form a cyclopropyl;
• Z1 is (C(RZ)2)p-T1;
• p is 1, 2, 3, 4, 5, or 6;
• each RZ is independently H, C1-C4 alkyl, C1-C4 alkyl substituted with one or more halogen, or halogen;
• T1 is CHOR1, C(O)R1, C(O)OR1, C(O)N(R1)2, NR1C(O)R1, C(S)R1, C(S)N(R1)2, NR1C(S)R1, C(O)NHS(O)2RS, C(O)NHCOR1, C(O)NHOH, or C(O)NHCN;
• RS is R1, C3-C8 cycloalkyl, heterocyclyl comprising one 5- or 6-membered rings and 1-2 heteroatoms selected from N, O, and S, or C6-C10 aryl, wherein the cycloalkyl, heterocyclyl, or aryl is optionally substituted with one or more groups independently selected from C1-C4 alkyl;
• each R1 is independently H, C1-C4 alkyl, or C1-C4 alkyl substituted with one or more halogen;
• m is 0, 1, 2, 3, or 4;
• each Y is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, CN, OH, O—(C1-C6 alkyl), S—(C1-C6 alkyl), O—(C2-C4 alkenyl), O—(C2-C4 alkynyl), NH2, NH—C1-C6 alkyl, N—(C1-C6 alkyl)2, S(O)—(C1-C6 alkyl), S(O)2—(C1-C6 alkyl), or Q-T, wherein the alkyl, alkenyl, or alkynyl moiety is optionally substituted with one or more groups independently selected from OH, NH2, N3, halogen, O—(C1-C6 alkyl), S—(C1-C6 alkyl), NH—C1-C6 alkyl, and N—(C1-C6 alkyl)2, or two Y, together with the two adjacent carbon atoms to which they are bonded, form a 5- to 7-membered carbocycle or phenyl;
• n is 0, 1, 2, 3, or 4;
• each Z is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, halogen, CN, OH, O—(C1-C6 alkyl), S—(C1-C6 alkyl), O—(C2-C4 alkenyl), O—(C2-C4 alkynyl), NH2, NH—C1-C6 alkyl, N—(C1-C6 alkyl)2, S(O)—(C1-C6 alkyl), S(O)2—(C1-C6 alkyl), or Q-T, wherein the alkyl, alkenyl, or alkynyl moiety is optionally substituted with one or more groups independently selected from OH, NH2, N3, halogen, O—(C1-C6 alkyl), S—(C1-C6 alkyl), NH—C1-C6 alkyl, and N—(C1-C6 alkyl)2;
• each Q is independently a bond, NH, N(C1-C3 alkyl), O, S, S(O), S(O)2, Q′, NH-Q′, N(C1-C3 alkyl)-Q′, O-Q′, S-Q′, S(O)-Q′, or S(O)2-Q′;
• each Q′ is independently a carbon linker comprising one or more C(RQ)2, C(RQ)2—C(RQ)2, CRQ═CRQ, or C≡C;
• each RQ is independently H or C1-C3 alkyl;
• each T is independently C(O)—C1-C6 alkyl, C(O)O—C1-C6 alkyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, heterocyclyl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, C6-C10 aryl, or heteroaryl comprising one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S, wherein the cycloalkyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one or more RT;
• each RT is independently C1-C6 alkyl, C1-C6 haloalkyl, OH, CN, halogen, O—(C1-C6 alkyl), O—(C1-C6 haloalkyl), S—(C1-C6 alkyl), NH2, NH—C1-C6 alkyl, N—(C1-C6 alkyl)2, NHS(O)2—(C1-C6 alkyl), (CH2)q—C3-C8 cycloalkyl, (CH2)q-heterocyclyl, (CH2)q-phenyl, or (CH2)q-heteroaryl, wherein the heterocyclyl or heteroaryl comprises one or two 5- or 6-membered rings and 1-4 heteroatoms selected from N, O, and S;
• and
• q is 0, 1, 2, or 3,
• wherein when X is C(O) and each RZ is H:
• m and n are not both 0;
• and
• the compound of Formula I is not mono-substituted at the 2- or 7-position with Cl;
• and
• the compound of Formula I is not di-substituted at the 2- and 8-positions or at the 1- and 7-positions with halogens selected from F and Cl.