CD73 inhibitors

A compound of Formula (IIa), or a pharmaceutically acceptable salt or stereoisomer thereof:

• wherein:
• A is —O—;
• Q1 is N and Q2 is N;
• Z is —NR1R2;
• R1 and R2 are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), —S(═O)2R15a, —S(═O)2NR16aR17a, or —C(═O)2R15a, wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R30a;
• or R1 and R2 are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R30b;
• R3 is halogen;
• R4 and R7 are —OH;
• R5 and R6 are hydrogen;
• X1 is a bond;
• Y1 is —S(═O)2—;
• Y2 is —(CR45R46)v2—;
• R45 and R46 are each independently hydrogen, halogen, —OH, —ORa, —NRcRd, C1-C6 alkyl, or C1-C6 haloalkyl;
• v2 is 1-3;
• R15a is selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl;
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R30g;
• R16a and R17a are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, or heterocycloalkyl;
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one, two, or three R30h;
• or R16a and R17a are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three halogens, C1-C6 alkyl, or C1-C6 haloalkyl;
• R21 and R22 are each independently hydrogen, C1-C20 alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), C1-C6 alkyl(heterocycloalkyl), —(CR23R24)wC(═O)OR25, —(CR23R24)wOC(═O)R26, —(CR23R24)wSC(═O)R26, or —(CR23R24)wOC(═O)OR25, wherein each alkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R30k;
• or R21 and R22 are taken together with the atoms to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R30l;
• each R23 and R24 are independently hydrogen, halogen, —OH, —ORa, —NRcRd, C1-C6 alkyl, or C1-C6 haloalkyl;
• each R25 is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 heteroalkyl;
• each R26 is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 heteroalkyl;
• each w is independently 1-4;
• each R30a, R30b, R30g, R30h, R30k, and R30l, are independently halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —NO2, —NRcRd, —S(═O)2Ra, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C1-C6 alkyl(aryl), C1-C6 alkyl(heteroaryl), C1-C6 alkyl(cycloalkyl), or C1-C6 alkyl(heterocycloalkyl);
• wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R31;
• each R31 is independently halogen, —CN, —OH, —ORa, —SH, —SRa, —S(═O)Ra, —NO2, —NRcRd, —S(═O)2Ra, —NHS(═O)2Ra, —S(═O)2NRcRd, —C(═O)Ra, —OC(═O)Ra, —C(═O)ORb, —OC(═O)ORb, —C(═O)NRcRd, —OC(═O)NRcRd, —NRbC(═O)NRcRd, —NRbC(═O)Ra, —NRbC(═O)ORb, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, C1-C6 heteroalkyl, or cycloalkyl optionally substituted with one, two, or three halogen, C1-C6 alkyl, or C1-C6 haloalkyl;
• each Ra is independently C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three halogen, —OH, C1-C6 alkyl, or C1-C6 haloalkyl;
• each Rb is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl aryl, and heteroaryl is independently optionally substituted with one, two, or three halogen, —OH, C1-C6 alkyl, or C1-C6 haloalkyl;
• and
• Rc and Rd are each independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;
• wherein the alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three halogen, —OH, C1-C6 alkyl, or C1-C6 haloalkyl;
• or Rc and Rd are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three halogen, C1-C6 or C1-C6 haloalkyl.