Macrocyclic compounds for treating disease

A compound of the formula I

• wherein
• each L is independently —C(R1)(R2)— or X;
• with the proviso that, when t is 1, then L is —C(R1)(R2)—;
• X is O, S, S(O) or S(O)2;
• each IV and R2 is independently H, deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl, —ORa, —OC(O)Ra, —OC(O)Ra, —OC(O)NRaRb, —OS(O)Ra, —OS(O)2Ra, —SRa, —S(O)Ra, —S(O)2Ra, —S(O)NRaRb, —S(O)2NRaRb, —OS(O)NRaRb, —OS(O)2NRaRb, —NRaRb, —NRaC(O)Rb, —NRaC(O)ORb, —NRaC(O)NRaRb, —NRaS(O)Rb, —NRaS(O)2Rb, —NRaS(O)NRaRb, —NRaS(O)2NRaRb, —C(O)Ra, —C(O)ORa, —C(O)NRaRb, —PRaRb, —P(O)RaRb, —P(O)2RaRb, —P(O)NRaRb, —P(O)2NRaRb, —P(O)ORa, —P(O)2ORa, —CN, or —NO2, or R1 and R2 taken together with the carbon or carbons to which they are attached form a C3-C6 cycloalkyl or a 4- to 6-membered heterocycloalkyl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, mono- or bicyclic heteroaryl, 4- to 6-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, —ORe, —OC(O)Re, —OC(O)NReRf, —OC(═N)NReRf, —OS(O)Re, —OS(O)2Re, —OS(O)NReRf, —OS(O)2NReRf, —SRc, —S(O)Re, —S(O)2Re, —S(O)NReRf, —S(O)2NReRf, —NReRf, —NReC(O)Rf, —NReC(O)ORf, —NReC(O)NReRf, —NReS(O)Rf, —NReS(O)2Rf, —NReS(O)NReRf, —NReS(O)2NReRf, —C(O)Re, —C(O)ORe, —C(O)NReRf, —PReRf, —P(O)ReRf, —P(O)2ReRf, —P(O)NReRf, —P(O)2NReRf, —P(O)ORe, —P(O)2ORe, —CN, or —NO2;
• M is CR3 or N;
• M1 is CR4;
• each R3, R4, and R5 is independently hydrogen, deuterium, halogen, —ORc, —OC(O)Rc, —OC(O)NRcRd, —OC(═N)NRcRd, —OS(O)Rc, —OS(O)2Rc, —OS(O)NRcRd, —OS(O)2NRcRd, —SRc, —S(O)Rc, —S(O)2Rc, —S(O)NRcRd, —S(O)2NRcRd, —NRcRd, —NRcC(O)Rd, —NRc′C(O)ORd, —NRcC(O)NRcRd, —NRcC(═N)NRcRd, —NRcS(O)Rd, —NRcS(O)2Rd, —NRcS(O)NRcRd, —NRcS(O)2NRcRd, —C(O)Rc, —C(O)ORc, —C(O)NRcRd, —C(═N)NRcRd, —PRcRd, —P(O)RcRd, —P(O)2RcRd, —P(O)NRcRd, —P(O)2NRcRd, —P(O)ORc, —P(O)2ORc, —CN, —NO2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl, or R4 and R5 taken together with the ring to which they are attached form a C5-C8 cycloalkyl, or a 5- to 8-membered heterocycloalkyl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, mono- or bicyclic heteroaryl, C5-C8 cycloalkyl, or 5- to 8-membered heterocycloalkyl is independently optionally substituted by deuterium, halogen, C1-C6 alkyl, C1-C6 haloalkyl, —ORe, —OC(O)Re, —OC(O)NReRf, —OC(═N)NReRf, —OS(O)Re, —OS(O)2Re, —OS(O)NReRf, —OS(O)2NReRf, —SRe, —S(O)Re, —S(O)2Re, —S(O)NReRf, —S(O)2NReRf, —NReRf, —NReC(O)Rf, —NReC(O)ORf, —NReC(O)NReRf, —NReS(O)Rf, —NReS(O)2Rf, —NReS(O)NReRf, —NReS(O)2NReRf, —C(O)Re, —C(O)ORe, —C(O)NReRf, —PReRf, —P(O)ReRf, —P(O)2ReRf, —P(O)NReRf, —P(O)2NReRf, —P(O)ORe, —P(O)2ORe, —CN, or —NO2;
• R6 is H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl is independently optionally substituted by deuterium, halogen, C3-C6 cycloalkyl, or 5- to 7-membered heterocycloalkyl, —ORe, —OC(O)Re, —OC(O)NReRf, —OC(═N)NReRf, —OS(O)Re, —OS(O)2Re, —OS(O)NReRf, —OS(O)2NReRf, —SRe, —S(O)Re, —S(O)2Re, —S(O)NReRf, —S(O)2NReRf, —NReRf, —NReC(O)Rf, —NReC(O)ORf, —NReC(O)NReRf, —NReS(O)Rf, —NReS(O)2Rf, —NReS(O)NReRf, —NReS(O)2NReRf, —C(O)Re, —C(O)ORe, —C(O)NReRf, —PReRf, —P(O)ReRf, —P(O)2ReRf, —P(O)NReRf, —P(O)2NReRf, —P(O)ORe, —P(O)2ORe, —CN, or —NO2;
• R7 and R8 combine to form a C3-C7 cycloalkyl, 5- to 8-membered heterocycloalkyl, C6-C10 aryl, or 5- to 7-membered heteroaryl;
• wherein each hydrogen atom in C3-C7 cycloalkyl, 5- to 8-membered heterocycloalkyl, C6-C10 aryl, or 5- to 7-membered heteroaryl is independently optionally substituted by deuterium, halogen, —ORe, —OC(O)Re, —OC(O)NReRf, —OC(═N)NReRf, —OS(O)Re, —OS(O)2Re, —OS(O)NReRf, —OS(O)2NReRf, —SRe, —S(O)Re, —S(O)2Re, —S(O)NReRf, —S(O)2NReRf, —NReRf, —NReC(O)Rf, —NReC(O)ORf, —NReC(O)NReRf, —NReS(O)Rf, —NReS(O)2Rf, —NReS(O)NReRf, —NReS(O)2NReRf, —C(O)Re, —C(O)ORe, —C(O)NReRf, —PReRf, —P(O)ReRf, —P(O)2ReRf, —P(O)NReRf, —P(O)2NReRf, —P(O)ORe, —P(O)2ORe, —CN, or —NO2;
• Y is O, S, NR9, or CR9R19;
• R9 and R19 are each independently H, deuterium, halogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl, wherein each hydrogen atom in C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, or mono- or bicyclic heteroaryl is optionally substituted by a halogen, —ORe, —OC(O)Re, —OC(O)NReRf, —OC(═N)NReRf, —OS(O)Re, —OS(O)2Re, —OS(O)NReRf, —OS(O)2NReRf, —SRe, —S(O)Re, —S(O)2Re, —S(O)NReRf, —S(O)2NReRf, —NReRf, —NReC(O)Rf, —NReC(O)ORf, —NReC(O)NReRf, —NReS(O)Rf, —NReS(O)2Rf, —NReS(O)NReRf, —NReS(O)2NReRf, —C(O)Re, —C(O)ORe, —C(O)NReRf, —PReRf, —P(O)ReRf, —P(O)2ReRf, —P(O)NReRf, —P(O)2NReRf, —P(O)ORe, or —P(O)2ORe;
• each Ra, Rb, Rc, Rd, Re, and Rf is independently selected from the group consisting of H, deuterium, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 7-membered heterocycloalkyl, C6-C10 aryl, 5- to 7-membered heteroaryl;
• each of Z′, Z2, Z3, Z4, Z5, and Z6 is independently N, NH, C or CH;
• p is 1, 2, 3, or 4;
• and
• t is 1, 2, 3, 4, or 5;
• or a pharmaceutically acceptable salt thereof.