Compounds, compositions, and methods

A compound of Formula I:

• or a pharmaceutically acceptable salt, isotopically enriched analog, stereoisomer, mixture of stereoisomers, or prodrug thereof, wherein:
• X is O or S;
• Y is O or S;
• A1, A2, A3, and A4 are each independently N, CH, or CR1;
• provided at least one of A1, A2, A3, and A4 is CR1;
• each R1 is independently halo, cyano, —NO2, —SF5, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, heteroaryl, —N(R11)2, —OR11, —C(O)R11, —C(O)OR11, —S(O)0-2R11, —NR11S(O)0-2—R11, —S(O)0-2N(R11)2, —NR11S(O)0-2N(R11)2, —NR11C(O)N(R11)2, —C(O)N(R11)2, —NR11C(O)R11, —OC(O)N(R11)2, or —NR11C(O)OR11;
• wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl is independently optionally substituted with one to eight Z1;
• or
• any two adjacent R1 together with the atoms to which they are attached form a cycloalkyl, heterocyclyl, aryl, or heteroaryl ring;
• wherein the cycloalkyl, heterocyclyl, aryl, or heteroaryl is independently optionally substituted with one to eight Z1;
• R2 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, heterocyclyl, aryl, heteroaryl, —NO2, —SF5, —OR11, —N(R11)2, —C(O)R11, —C(O)OR11, —S(O)0-2—R11, —NR11S(O)0-2—R11, —S(O)0-2N(R11)2, —NR11S(O)0-2N(R11)2, —NR11C(O)N(R11)2, —NR11C(O)OR11, —NR11C(O)R11, —OC(O)R11, —OC(O)N(R11)2, —C(O)N(R11)2, halo, or cyano;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one to eight Z1;
• R3 is hydrogen, halo, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one to eight Z1;
• or
• R2 and R3 together form a C3-10 cycloalkyl or heterocyclyl ring;
• wherein the C3-10 cycloalkyl or heterocyclyl is optionally substituted with one to eight Z1;
• R4 is hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one to eight Z1;
• or
• R5 is C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with one to eight Z1;
• or
• R4 and R5 together form a heterocyclyl or heteroaryl ring optionally substituted with one to eight Z1;
• R6 is hydrogen, halo, cyano, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C2-6 heteroalkyl, C3-10 cycloalkyl, or heterocyclyl;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C2-6 heteroalkyl, C3-10 cycloalkyl, or heterocyclyl may further be optionally substituted with one to five Z1b;
• R7 is hydrogen, halo, cyano, hydroxy, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C2-6 heteroalkyl, C3-10 cycloalkyl, or heterocyclyl;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C2-6 heteroalkyl, C3-10 cycloalkyl, or heterocyclyl, or may further be optionally substituted with one to five Z1b;
• or R6 and R7 join to form a C3-10 cycloalkyl or heterocyclyl ring;
• wherein the C3-10 cycloalkyl or heterocyclyl ring may further be optionally substituted with one to five Z1b;
• R9 and R10 are each independently hydrogen, halo, cyano, C1-6 alkyl, or C1-6 haloalkyl, wherein each C1-6 alkyl or C1-6 haloalkyl is independently optionally substituted with one to five Z1;
• or
• R9 and R10 together form a C3-10 cycloalkyl or heterocyclyl ring;
• wherein the C3-10 cycloalkyl or heterocyclyl is optionally substituted with one to eight Z1;
• each Z1 is independently halo, cyano, —NO2, —SF5, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, heteroaryl, —N(R11)2, —OR1, —C(O)R11, —C(O)OR11, —S(O)0-2R11, —NR11S(O)0-2—R11, —S(O)0-2N(R11)2, —NR11S(O)0-2N(R11)2, —NR11C(O)N(R11)2, —C(O)N(R11)2, —NR11C(O)R11, —OC(O)N(R11)2, or —NR11C(O)OR11;
• wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl is independently optionally substituted with one to five Z1a;
• each R11 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl of R11 is independently optionally substituted with one to five Z1a;
• each Z1a is independently hydroxy, halo, cyano, —NO2, —SF5, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, heteroaryl, —N(R13)2, —OR13, —C(O)R13, —C(O)OR13, —S(O)0-2R13, —NR13S(O)0-2—R13, —S(O)0-2N(R13)2, —NR13S(O)0-2N(R13)2, —NR13C(O)N(R13)2, —C(O)N(R13)2, —NR13C(O)R13, —OC(O)N(R13)2, or —NR13C(O)OR13;
• wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl is independently optionally substituted with one to five Z1b;
• each R13 is independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl;
• wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl of R13 is independently optionally substituted with one to five Z1b;
• each Z1b is independently halo, cyano, hydroxy, —SH, —NH2, —NO2, —SF5, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, heterocyclyl, aryl, heteroaryl, -L-C1-6 alkyl, -L-C2-6 alkenyl, -L-C2-6 alkynyl, -L-C1-6 haloalkyl, -L-C3-10 cycloalkyl, -L-heterocyclyl, -L-aryl, or -L-heteroaryl;
• and
• each L is independently —O—, —NH—, —S—, —S(O)—, —S(O)2—, —N(C1-6 alkyl)-, —N(C2-6 alkenyl)-, —N(C2-6 alkynyl)-, —N(C1-6 haloalkyl)-, —N(C3-10 cycloalkyl)-, —N(heterocyclyl)-, —N(aryl)-, —N(heteroaryl)-, —C(O)—, —C(O)O—, —C(O)NH—, —C(O)N(C1-6 alkyl)-, —C(O)N(C2-6 alkenyl)-, —C(O)N(C2-6 alkynyl)-, —C(O)N(C1-6 haloalkyl)-, —C(O)N(C3-10 cycloalkyl)-, —C(O)N(heterocyclyl)-, —C(O)N(aryl)-, —C(O)N(heteroaryl)-, —NHC(O)—, —NHC(O)O—, —NHC(O)NH—, —NHS(O)—, or —S(O)2NH—;
• wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 haloalkyl, C3-10 cycloalkyl, heterocyclyl, aryl, and heteroaryl of Z1b and L is further independently optionally substituted with one to five hydroxy, halo, cyano, hydroxy, —SH, —NH2, —NO2, —SF5, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C3-10 cycloalkyl, heterocyclyl, aryl, or heteroaryl.