Compounds and methods for CD73 modulation and indications therefor

A compound having Formula IIIa or IIIb:

• or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer, or a deuterated analog thereof, wherein:
• L is —O—C(O)—N(Ra)— or —N(Ra)—C(O)—O—;
• G is one of the following groups, provided that L is not attached to a heteroatom of G when G contains a heteroatom:
• (a) —C0-C1alkyl-C3-C7cycloalkyl substituted with 0-4 T1, 0-1 T2, and 0-1 oxo;
• (b) a 5-9 membered bridged carbocyclic ring substituted with 0-4 T1, 0-1 T2, and 0-1 oxo;
• (c) a 5-9 membered carbocyclic spiro ring containing two cycloalkyl groups joined by one common spiro carbon atom, wherein the carbocyclic spiro ring system is substituted with 0-4 T1, 0-1 T2, and 0-1 oxo;
• (d) a 6-9 heterocyclic spiro ring containing a heterocyclic group and a cycloalkyl group joined by one common spiro carbon atom, wherein the heterocyclic spiro ring system is substituted with 0-3 T5 and 0-1 T6;
• (e) —C0-C2alkylene-phenyl substituted with 0-4 T1 and 0-1 T4;
• (f) —C0-C2alkylene-4-6 membered heterocycloalkyl substituted with 0-4 T5 and 0-1 T6, and 0-1 oxo;
• (g) a 5-9 membered bridged heterocyclic ring substituted with 0-4 T5 and 0-1 T6;
• (h) —C0-C2alkylene-5-6 membered heteroaryl substituted with 0-3 T5 and 0-1 T3;
• or
• (i) —C1-C6alkyl optionally substituted with one or more groups independently selected from the group consisting of halogen, hydroxyl, C1-C6alkoxyl and CN;
• each T1 is independently halogen, hydroxyl, C1-C6alkyl optionally substituted with 1-3 Rb, C2-C6alkenyl optionally substituted with 1-3 Rb, C2-C6alkynyl optionally substituted with 1-3 Rb, CN, C1-C6cyanoalkyl, C1-C6alkoxyl optionally substituted with 1-3 Rb, or C1-C6alkoxyC1-C6alkyl optionally substituted with 1-3 Rb;
• T2 is —(CH2)0-1—N(R9)SO2—R7, —(CH2)0-1—SO2—R7, —(CH2)0-1—N(R9)SO2N(R8)R9, —(CH2)0-1—N(R9)C(O)N(R8)R9, —(CH2)0-1—N(R9)C(O)R8, —(CH2)0-1—N(R9)C(O)OR9, —(CH2)0-1—N(R8)R9, —(CH2)0-1—C(O)N(R8)R9, —(CH2)0-1—C(O)OR9, —(CH2)0-1—C(O)R10, —(CH2)0-1—C(O)H, —(CH2)0-1—N(R9)C(O)R10, —(CH2)0-1—C3-C6cycloalkyl optionally substituted with 1-4 Z3, —(CH2)0-1-phenyl optionally substituted with 1-3 Z5, or —(CH2)0-1-5-6 membered heteroaryl optionally substituted with 1-3 Z5;
• T3 is C3-C7cycloalkyl optionally substituted with 1-4 Z3,
• T4 is C(O)OR9;
• each T5 is independently halogen, hydroxyl, C1-C6alkyl optionally substituted with 1-3 Rb, C2-C6 alkenyl optionally substituted with 1-3 Rb, C2-C6alkynyl optionally substituted with 1-3 Rb, CN, C1-C6cyanoalkyl, C1-C6alkoxyl optionally substituted with 1-3 Rb, or C1-C6alkoxyC1-C6alkyl optionally substituted with 1-3 Rb, provided that when T5 is attached to a heteroatom of G, then T5 cannot be halogen, hydroxyl, CN, or C1-C6alkoxyl optionally substituted with 1-3 Rb;
• T6 is —(CH2)0-1—N(R9)SO2—R7, —(CH2)0-1—SO2—R7, —(CH2)0-1—N(R9)SO2N(R8)R9, —(CH2)0-1—N(R9)C(O)N(R8)R9, —(CH2)0-1—N(R9)C(O)R8, —(CH2)0-1—N(R9)C(O)OR9, —(CH2)0-1—N(R8)R9, —(CH2)0-1—C(O)—N(R8)R9, —(CH2)0-1—C(O)OR9, —(CH2)0-1—C(O)R10, —(CH2)0-1—N(R9)C(O)R10, —N(H)C(H)C═O, —(CH2)0-1—C3-C6cycloalkyl optionally substituted with 1-4 Z3, 4-chloropyridazin-3-one-5-yl, or —(CH2)0-2-5-6 membered heteroaryl optionally substituted with 1-3 Z5, provided that when T6 is attached to a heteroatom of G, then T6 cannot be —N(R9)SO2—R7, —SO2—R7, —N(R9)SO2N(R8)R9, —N(R9)C(O)N(R8)R9, —N(R9)C(O)R8, —N(R9)C(O)OR9, —N(R8)R9, —N(R9)C(O)R10, or —N(H)C(H)C═O;
• each Ra is independently H or C1-C6alkyl;
• each Rb is independently halogen, CN or hydroxyl;
• R1 is hydrogen, C1-C6alkoxyC1-C6alkyl, 4-6 membered heterocycloalkyl, cycloalkyl, C(O)N(H)cycloalkyl, phenyl optionally substituted with 1-4 Z1 groups, —C(O)N(H)phenyl optionally substituted with 1-4 Z1 groups, C2-C6alkenyl, or C1-C6alkyl substituted with 0-4 Z2 and 0-1 Z6;
• R2 is H, halogen, C1-C3alkyl, C2-C3alkenyl, C1-C3alkoxyl, C1-C3haloalkyl, or CN;
• each R4 is independently halogen, CN, or C1-C6alkyl optionally substituted with halogen;
• each R5 is independently H, C1-C6alkyl, C1-C6alkoxyl, C3-C6cycloalkyl, or C3-C6cycloalkylC1-C6alkyl, wherein the C1-C6alkyl, C1-C6alkoxyl, C3-C6cycloalkyl, or C3-C6cycloalkylC1-C6alkyl groups can each be optionally substituted with 1-3 groups independently selected from halogen, hydroxyl, or CN;
• each R6 is independently H, C1-C6alkyl, or C1-C6alkoxyl, wherein the C1-C6alkyl or C1-C6alkoxyl groups can each be optionally substituted with 1-3 groups independently selected from halogen, hydroxyl or CN;
• R7 is C1-C6alkyl optionally substituted with 1-4 Z4, alkenyl optionally substituted with 1-4 Z4, —C0-C3alkyl-C3-C6cycloalkyl optionally substituted with 1-4 Z3, —C0-C2alkyl-phenyl optionally substituted with 1-4 Z3, —C0-C2alkyl-5-6 membered heteroaryl optionally substituted with 1-3 Z5, or —C0-C2alkyl-4-6 membered heterocycloalkyl optionally substituted with 1-3 Z5;
• R8 is H, C1-C6alkyl optionally substituted with 1-4 Z4, C2-C6alkenyl optionally substituted with 1-4 Z4, —C0-C2alkyl-C3-C6cycloalkyl optionally substituted with 1-4 Z3, —C0-C2alkyl-phenyl optionally substituted with 1-4 Z3, —C0-C2alkyl-5-6 membered heteroaryl optionally substituted with 1-3 Z5, —C0-C2alkyl-4-6 membered heterocycloalkyl optionally substituted with 1-3 Z5, or a 5-9 membered bridged carbocyclic ring substituted with 0-4 T1;
• each R9 is independently H or C1-C3alkyl optionally substituted with 1-2 Z4;
• R10 is C1-C6alkyl substituted with 0-4 Z4 and 0-1 Z7, —C0-C3alkyl-C3-C6cycloalkyl optionally substituted with 1-4 Z3, —C0-C2alkyl-phenyl optionally substituted with 1-4 Z3, —C0-C2alkyl-heteroaryl optionally substituted with 1-3 Z5, or —C0-C2alkyl-4-6 membered heterocycloalkyl optionally substituted with 1-3 Z5;
• each Z1 is independently halogen, C1-C6alkyl, C1-C6alkoxyl, —N(R5)(R6), or —C(O)OR5;
• Z2 is hydroxyl, halogen, or CN;
• each Z3 is independently C1-C6alkyl, halogen, C1-C6haloalkyl, hydroxyl, C1-C6hydroxyalkyl, C1-C6alkoxyl, C1-C6haloalkoxyl, C1-C6alkoxyC1-C6alkylhaloalkyl, C1-C6alkoxyC1-C6alkyl, —C(O)OR9, or CN, provided that not more than 1 Z3 can be —C(O)OR9;
• each Z4 is independently, hydroxyl, halogen, C1-C6alkoxyl, —N(C1-C6alkyl)2, or CN;
• each Z5 is independently C1-C6alkyl, C1-C6haloalkyl, hydroxyl, C1-C6hydroxyalkyl, halogen, C1-C6alkoxyl, C1-C6alkoxyC1-C6alkyl, C3-C6cycloalkyl, or CN, provided that when Z5 is attached to a heteroatom, then Z5 is not halogen, hydroxyl, C1-C6alkoxyl, or CN;
• Z6 is —C(O)OH, —C(O)O—C1-C6alkyl, —NH2, —N(H)C1-C6alkyl, —N(C1-C6alkyl)2, —C(O)N(H)OH, 4-6 membered heterocycloalkyl optionally substituted with 1-3 halogens, or phenyl optionally substituted with 1-3 halogens;
• Z7 is —(CH2)0-1—N(R9)SO2—R7, —(CH2)0-1—SO2—R7, —(CH2)0-1—N(R9)SO2N(R8)R9, —(CH2)0-1—N(R9)C(O)N(R8)R9, —(CH2)0-1—N(R9)C(O)R8, —N(R9)C(O)OR9, —(CH2)0-1—N(R8)R9, —(CH2)0-1—C(O)—N(R8)R9, —C(O)OR9, —(CH2)0-1—C(O)R10, —(CH2)0-1—N(R9)C(O)R10, phenyl optionally substituted with 1-4 Z3, or 5-6 membered heteroaryl optionally substituted with 1-3 Z5;
• and
• m is 0-2,
• provided that when L is —N(Ra)—C(O)—O—, then G is not an unsubstituted C1-C6alkyl group.