Substituted benzamides and methods of use thereof

A compound of formula I:

• or a salt thereof wherein:
• R1 is C1-8 alkyl, C2-8 alkenyl, C1-8 haloalkyl, C1-8 alkoxy, 3-20 membered carbocycle, C-linked 3-20 membered heterocycle, or —NR1AR1B, herein R1A and R1B are each independently selected from the group consisting of hydrogen, C1-8 alkyl, C1-8 alkoxy, and wherein R1A and R1B are optionally combined to form a 3-20 membered heterocycle;
• and wherein R1 is optionally substituted with from 1 to 5 substituents selected from the group consisting of C1-4 alkyl, C3-4 haloalkyl, F, Cl, Br, I, —OH, —CN, —NO2, —NRR1aRR1b, —ORR1a, —SRR1a, —Si(RR1a)3 and C3-6 carbocycle;
• wherein RR1a and RR1b are independently selected from the group consisting of hydrogen, C1-8 alkyl, and C1-8 haloalkyl;
• RN is hydrogen, C1-4 alkyl or C1-4 haloalkyl;
• L is a linker selected from the group consisting of C1-4 alkylene, C2-4 alkenylene and C2-4 alkynylene, wherein L is optionally substituted with from 1 to 3 substituents selected from the group consisting of ═O, C1-4 alkyl, halo, and C1-4 haloalkyl;
• the subscript m is 0 or 1;
• X1 and X2 are each independently selected from the group consisting of absent, —O—, —S(O)—, —S(O)2— and —N(RX)— wherein Rx is H, C1-8 alkyl, C1-8 alkanoyl, or —S(O)2(C1-8 alkyl), and wherein if the subscript m is 0 then one of X1 or X2 is absent;
• the subscript n is 0, 1, 2, 3, 4, or 5;
• the ring A is a 3-20 membered carbocyclyl, a 6-20 membered aryl, a 5-20 membered heteroaryl, or a 3-20 membered heterocyclyl;
• each RAA is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 heteroalkyl, CN, F, Cl, Br and I;
• and
• RA is selected from the group consisting of absent, CN, F, Cl, Br, I, RA1O—(XRB)—, (3-20 membered aryl)-(XRA)—, (3-20 membered heteroaryl)-(XRA)—, (3-20 membered carbocycle)-(XRA)—, (3-20 membered heterocycle)-(XRA)—, —RA2, and —S(O)2—RA2, wherein said 3-20 membered aryl, 3-20 membered heteroaryl, 3-20 membered carbocycle and 3-20 membered heterocycle of RA is optionally substituted with from 1 to 5 substitutents selected from, F, Cl, Br, I, —NH2, —OH, —CN, —NO2, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4(halo)alkoxy, C1-4 alkylamino, C1-4 dialkylamino, C1-4 alkanoyl, C1-4 akyl-OC(═O)—, C1-4 alkyl-S(O)2—, C3-6 carbocycle, and phenyl that is optionally substituted with one or more substituents selected from fluoro, chloro, and bromo;
• RA1 is selected from the group consisting of hydrogen, C1-8 alkyl, C2-8 alkenyl, C1-8 haloalkyl, C3-8 cycloalkyl, phenyl and benzyl;
• RA2 is a C1-8 alkyl that is optionally substituted with one or more substituents selected from oxo (═O), fluoro, amino, C1-4 alkylamino and C1-4 dialkylamino;
• XRA is selected from the group consisting of absent, —O—, —S—, —N(H)—, —N(C1-4 alkyl)-, —S(O)—, —S(O)2—, —C(═O)—, C1-4 alkylene, C1-4 heteroalkylene, C2-4 alkenylene and C2-4 alkynylene;
• XRB is selected from the group consisting of absent, C1-4 alkylene, C1-4 heteroalkylene, C2-4 alkenylene and C2-4 alkynylene;
• wherein any C1-4 alkylene, C1-4 heteroalkylene, C2-4 alkenylene and C2-4 alkynylene of XRA or XRB is optionally substituted with 1 to 3 substituents selected from the group consisting of C1-4 alkyl, C1-4 haloalkyl, C1-4 heteroalkyl, oxo (═O), hydroxy, and phenyl that is optionally substituted with 1 to 5 substitutents selected from, F, Cl, Br, I, —NH2, —OH, —CN, —NO2, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, C1-4(halo)alkoxy, C1-4 alkylamino and C1-4 dialkylamino;
• or wherein XRA or XRB is optionally substituted with 2 substituents that combine to form a 3-5 membered carbocycle or a 3-5 membered heterocycle;
• the ring B is selected from:
• D1 is N or C(RD1);
• D3 is N or C(RD3);
• RD1, RD2, RD3 and RD4 are each independently selected from the group consisting of H, F, Cl, Br, I, —CN, C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, 3-12 membered cycloalkyl, 3-12 membered heterocycle, phenyl and 5-6 membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O and S, wherein said 5-6 membered heteroaryl is further optionally substituted with from 1 to 3 substituents selected from F, Cl, Br, I, —CN, C1-4 alkyl, C1-4 haloalkyl and C1-4 alkoxy;
• R22 and R23 are each independently selected from the group consisting of H, F, Cl, Br, I, —CN, C1-8 alkyl, C1-8 haloalkyl and C1-8 alkoxy;
• R24 is selected from the group consisting of H, F, CL, Br, I, —CN, C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, 3-12 membered carbocycle, 3-12 membered heterocycle, phenyl and 5-6 membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O and S, wherein said 5-6 membered heteroaryl is further optionally substituted with from 1 to 3 R5 substituents selected from F, Cl, Br, I, —CN, C1-4 alkyl, C1-4 haloalkyl and C1-4 alkoxy;
• R32 and R33 are each independently selected from the group consisting of H, F, Cl, Br, I, —CN, C1-8 alkyl, C1-8 haloalkyl and C1-8 alkoxy;
• R34 is selected from the group consisting of H, F, Cl, Br, 1, —CN, C1-8 alkyl, C2-8 alkenyl, C1-8 haloalkyl, C1-8 alkoxy, 3-12 membered carbocycle, 3-12 membered heterocycle, phenyl and 5-6 membered heteroaryl comprising 1 to 3 heteroatoms selected from N, O and S, wherein said 5-6 membered heteroaryl is further optionally substituted with from 1 to 3 substituents selected from F, Cl, Br, I, —CN, C1-4 alkyl, C1-4 haloalkyl and C1-4 alkoxy;
• R42 is selected from the group consisting of H, F, Cl, Br, I, —CN, C1-8 alkyl, C1-8 haloalkyl and C1-8 alkoxy;
• R43 is selected from the group consisting of H, F, Cl, Br, I, —CN, C1-8 alkyl, C1-8 haloalkyl and C1-8 alkoxy;
• R44 is selected from the group consisting of H, F, Cl, Br, I, —CN, C1-8 alkyl, C1-8 haloalkyl and C1-8 alkoxy;
• and
• R45 is selected from the group consisting of H, C1-8 alkyl, C1-8 haloalkyl, C1-8 alkoxy, and 3-12 membered cycloalkyl, wherein said C1-8 alkoxy, and 3-12 membered cycloalkyl are optionally substituted with 1-3 substituents selected from F, Cl, Br and I.