Macrocycles for use in treating disease

A compound of the formula I

• wherein
• each R1 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, 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, —NO2;
• or R1 and R2 taken together with the carbon atom to which they are attached combine to form a C3-C6 cycloalkyl;
• 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, and mono- or bicyclic heteroaryl 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;
• each R3 and R3′ 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, 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, —NO2, 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, 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;
• or R3 and R3′ taken together with the carbon atom to which they are attached combine to form a C3-C6 cycloalkyl;
• wherein each hydrogen atom in C3-C6 cycloalkyl 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;
• each 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, —NRcC(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, 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, or C1-C6 alkyl, wherein each hydrogen atom in C1-C6 alkyl is independently optionally substituted by deuterium, halogen, —ORe, —SRe, or —NReRf;
• each R7 is independently hydrogen or deuterium;
• 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, and 5- to 7-membered heteroaryl;
• and
• n is 0, 1, 2, or 3;
• or a pharmaceutically acceptable salt thereof.