Macrocyclic heterocycles and uses thereof

A compound of the formula:

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• {circle around (A)} is selected from C5-7 carbocycle and 5- to 7-membered heterocycle, each of which is optionally substituted with one or more R11;
• {circle around (B)} is absent or selected from C3-8 carbocycle and 3- to 8-membered heterocycle, each of which is optionally substituted with one or more R11a;
• L1 is selected from a bond, C1-6 alkylene, and C1-6 haloalkylene;
• L2 is -L3-D-L4-;
• L3 is selected from C1-10 alkylene, C2-10 alkenylene, C2-10 alkynylene, 2- to 10-membered heteroalkylene, and 3- to 10-membered heteroalkenylene, each of which is optionally substituted with one or more R11b;
• D is absent or selected from C3-12 carbocycle and 3- to 12-membered heterocycle, each of which is optionally substituted with one or more R11d;
• L4 is selected from C1-10 alkylene, C2-10 alkenylene, C2-10 alkynylene, 2- to 10-membered heteroalkylene, and 3- to 10-membered heteroalkenylene, each of which is optionally substituted with one or more R11b;
• W5 is selected from N and C(R5);
• R1 is C1-3 alkyl optionally substituted with one or more R11c;
• R5, R7, and R8 are each independently selected from hydrogen, halogen, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, —OR12, —SR12, —N(R12)(R13), —C(O)OR12, —OC(O)N(R12)(R13), —N(R14)C(O)N(R12)(R13), —N(R14)C(O)OR15, —N(R14)S(O)2R15, —C(O)R15, —S(O)R15, —OC(O)R15, —C(O)N(R12)(R13), —C(O)C(O)N(R12)(R13), —N(R14)C(O)R15, —S(O)2R15, —S(O)2N(R12)(R13), —S(═O)(═NH)N(R12)(R13), —CH2C(O)N(R12)(R13), —CH2N(R14)C(O)R15, —CH2S(O)2R15, and —CH2S(O)2N(R12)(R13), wherein each C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle is independently optionally substituted with one, two, or three R20;
• R11, R11a, and R11d are each independently selected at each occurrence from halogen, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, —OR12, —SR12, —N(R12)(R13), —C(O)OR12, —OC(O)N(R12)(R13), —N(R14)C(O)N(R12)(R13), —N(R14)C(O)OR15, —N(R14)S(O)2R15, —C(O)R15, —S(O)R15, —OC(O)R15, —C(O)N(R12)(R13), —C(O)C(O)N(R12)(R13), —N(R14)C(O)R15, —S(O)2R15, —S(O)2N(R12)(R13), —S(═O)(═NH)N(R12)(R13), —CH2C(O)N(R12)(R13), —CH2N(R14)C(O)R15, —CH2S(O)2R15, —CH2S(O)2N(R12)(R13), —CH2N(R12)S(O)2(R13), and —P(O)(R17)(R17a), wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle are optionally substituted with one, two, or three R20;
• R11b is independently selected at each occurrence from halogen, oxo, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, 3- to 10-membered heterocycle, —OR12, —SR12, —N(R12)(R13), —C(O)OR12, —OC(O)N(R12)(R13), —N(R14)C(O)N(R12)(R13), —N(R14)C(O)OR15, —N(R14)S(O)2R15, —C(O)R15, —S(O)R15, —OC(O)R15, —C(O)N(R12)(R13), —C(O)C(O)N(R12)(R13), —N(R14)C(O)R15, —S(O)2R15, —S(O)2N(R12)(R13), —S(═O)(═NH)N(R12)(R13), —CH2C(O)N(R12)(R13), —CH2N(R14)C(O)R15, —CH2S(O)2R15, —CH2S(O)2N(R12)(R13), —CH2N(R12)S(O)2(R13), and —P(O)(R17)(R17a), wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle are optionally substituted with one, two, or three R20;
• R11c is independently selected at each occurrence from halogen, —OR12, and —N(R12)(R13);
• R12 is independently selected at each occurrence from hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle are optionally substituted with one, two, or three R20;
• R13 is independently selected at each occurrence from hydrogen, C1-6 alkyl, and C1-6 haloalkyl;
• or
• R12 and R13, together with the nitrogen atom to which they are attached, form a 3- to 10-membered heterocycle optionally substituted with one, two, or three R20;
• R14 is independently selected at each occurrence from hydrogen, C1-6 alkyl, and C1-6 haloalkyl;
• R15 is independently selected at each occurrence from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle are optionally substituted with one, two, or three R20;
• R17 and R17a are each independently selected at each occurrence from C1-6 alkyl and C3-6 cycloalkyl, wherein C1-6 alkyl and C3-6 cycloalkyl are optionally substituted with one, two or three R20;
• or R17 and R17a, together with the phosphorous atom to which they are attached, form a 3- to 10-membered heterocycle;
• R20 is independently selected at each occurrence from halogen, oxo, ═NH, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, —CH2—(C3-10 carbocycle), 3- to 10-membered heterocycle, —CH2-(3- to 10-membered heterocycle), —OR21, —SR21, —N(R22)(R23), —C(O)OR22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —OC(O)N(R22)(R23), —N(R24)C(O)N(R22)(R23), —N(R24)C(O)OR25, —N(R24)C(O)R25, —N(R24)S(O)2R25, —C(O)R25, —S(O)2R25, —S(O)2N(R22)(R23), —OCH2C(O)OR22, and —OC(O)R25, wherein C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, —CH2—(C3-10 carbocycle), 3- to 10-membered heterocycle, and —CH2-(3- to 10-membered heterocycle) are optionally substituted with one, two, or three groups independently selected from halogen, oxo, ═NH, —CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, —OR21, —SR21, —N(R22)(R23), —C(O)OR22, —C(O)N(R22)(R23), —C(O)C(O)N(R22)(R23), —OC(O)N(R22)(R23), —N(R24)C(O)N(R22)(R23), —N(R24)C(O)OR25, —N(R24)C(O)R25, —N(R24)S(O)2R25, —C(O)R25, —S(O)2R25, —S(O)2N(R22)(R23), and —OC(O)R25;
• R21 is independently selected at each occurrence from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein C3-10 carbocycle and 3- to 10-membered heterocycle are optionally substituted with one, two, or three groups independently selected from halogen and C1-6 alkyl;
• R22 is independently selected at each occurrence from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein C3-10 carbocycle and 3- to 10-membered heterocycle are optionally substituted with one, two, or three groups independently selected from halogen and C1-6 alkyl;
• R23 is independently selected at each occurrence from H and C1-6 alkyl;
• R24 is independently selected at each occurrence from H and C1-6 alkyl;
• and
• R25 is independently selected at each occurrence from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocycle, and 3- to 10-membered heterocycle, wherein C1-6 alkyl, C3-10 carbocycle, and 3- to 10-membered heterocycle are optionally substituted with one, two, or three groups independently selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C3-10 carbocycle, and 3- to 10-membered heterocycle.