Compounds and methods for cd73 modulation and indications therefor

A compound having Formula I:

• or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer, or a deuterated analog thereof, wherein:
• A is a 5-6 membered aromatic ring or a 4-7 membered nitrogen containing heterocycloalkyl, wherein A is substituted with 0-4 R4 and 0-1 R11, provided that when ring A is a 5-6 membered nitrogen containing heterocycloalkyl, then the pyridazinone moiety of Formula I is attached to a nitrogen atom of A, and when L is —O—C(O)—N(Ra)—, then R11 is absent;
• L is —N(H)—C(O)—N(H)—, —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-C3alkyl-cycloalkyl substituted with 0-5 T1, 0-1 T2, and 0-1 oxo;
• (b) a bridged carbocylic ring substituted with 0-5 T1, 0-1 T2, and 0-1 oxo;
• (c) a 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 T1, and 0-1 oxo;
• (d) a 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, 0-1 T6;
• (e) —C0-C3alkylene-phenyl substituted with 0-4 T1 and 0-1 T4;
• (f) —C0-C1alkylene-heterocycloalkyl substituted with 0-4 T5, 0-1 T6 and 0-1 oxo;
• (g) a bridged heterocylic ring substituted with 0-4 T5 and 0-1 T6;
• (h) —C0-C3alkylene-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, alkoxyl, —C(O)OR9 and CN;
• each T1 is independently halogen, hydroxyl, alkyl optionally substituted with 1-3 Rb, alkenyl optionally substituted with 1-3 Rb, alkynyl optionally substituted with 1-3 Rb, CN, cyanoalkyl, alkoxyl optionally substituted with 1-3 Rb, or alkoxyalkyl optionally substituted with 1-3 Rb:
• T2 is —(CH2)0-2—N(R9)SO2—R7, —(CH2)0-2—SO2—R7, —(CH2)0-2—N(R9)SO2N(R8)R9, —(CH2)0-2—N(R9)C(O)N(R8)R9, —(CH2)0-2—N(R9)C(O)R8, —(CH2)0-2—N(R9)C(O)OR9, —(CH2)0-2—N(R8)R9, —(CH2)0-2—C(O)N(R8)R9, —(CH2)0-2—C(O)OR9, —(CH2)0-2—C(O)R10, —(CH2)0-2—C(O)H, —(CH2)0-2—N(R9)C(O)R10, —(CH2)0-2cycloalkyl optionally substituted with 1-4 Z3, —(CH2)0-2-phenyl optionally substituted with 1-3 Z5, or —(CH2)0-2heteroaryl optionally substituted with 1-3 Z5;
• T3 is cycloalkyl optionally substituted with 1-4 Z3,
• T3 is C(O)OR9 or N(Ra)2;
• each T5 is independently halogen, hydroxyl, alkyl optionally substituted with 1-3 Rb, alkenyl optionally substituted with 1-3 Rb, alkynyl optionally substituted with 1-3 Rb, CN, cyanoalkyl, alkoxyl optionally substituted with 1-3 Rb, or alkoxyalkyl optionally substituted with 1-3 Rb, provided that when T5 is attached to a heteroatom of G, T5 cannot be halogen, hydroxyl, CN, or alkoxyl optionally substituted with 1-3 Rb;
• T6 is —(CH2)0-2—N(R9)SO2—R7, —(CH2)0-2—SO2—R7, —(CH2)0-2—N(R9)SO2N(R8)R9, —(CH2)0-2—N(R9)C(O)N(R8)R9, —(CH2)0-2—N(R9)C(O)R8, —(CH2)0-2—N(R9)C(O)OR9, —(CH2)0-2—N(R8)R9, —(CH2)0-2—C(O)—N(R8)R9, —(CH2)0-2—C(O)OR9, —(CH2)0-2—C(O)R10, —(CH2)0-2—N(R9)C(O)R10, —N(H)C(H)C═O, —(CH2)0-2cycloalkyl optionally substituted with 1-4 Z3, 4-chloropyridazin-3-one-5-yl, or —(CH2)0-2heteroaryl 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 alkyl;
• each Rb is independently halogen, CN or hydroxyl;
• R1 is hydrogen, alkoxyalkyl, heterocycloalkyl, cycloalkyl, —C(O)N(H)cycloalkyl, phenyl optionally substituted with 1-5 Z1 groups, or —C(O)N(H)phenyl optionally substituted with 1-5 Z1 groups, alkenyl, or alkyl substituted with 0-4 Z2 and 0-1 Z6;
• R2 is H, halogen, alkyl, alkenyl, alkoxyl, haloalkyl, or CN;
• R3 is H, halogen, alkyl, CN, or haloalkyl;
• each R4 is independently halogen, CN, or alkyl optionally substituted with halogen;
• each R5 is independently H, alkyl, alkoxyl, cycloalkyl, or cycloalkylalkyl, wherein the alkyl, alkoxyl, cycloalkyl or cycloalkylalkyl groups can each be optionally substituted with 1-3 groups independently selected from halogen, hydroxyl or CN;
• each R6 is independently H, alkyl, or alkoxyl, wherein the alkyl or alkoxyl groups can each be optionally substituted with 1-3 groups independently selected from halogen, hydroxyl or CN;
• R7 is alkyl optionally substituted with 1-4 Z4, alkenyl optionally substituted with 1-4 Z4, —C0-C3alkyl-cycloalkyl optionally substituted with 1-4 Z3, —C0-C3alkyl-phenyl optionally substituted with 1-4 Z3, —C0-C3alkyl-heteroaryl optionally substituted with 1-3 Z5, or —C0-C3alkyl-heterocycloalkyl optionally substituted with 1-3 Z5;
• R8 is H, alkyl optionally substituted with 1-4 Z4, alkenyl optionally substituted with 1-4 Z4, —C0-C3alkyl-cycloalkyl optionally substituted with 1-4 Z3, —C0-C3alkyl-phenyl optionally substituted with 1-4 Z3, —C0-C3alkyl-heteroaryl optionally substituted with 1-3 Z5, —C0-C3alkyl-heterocycloalkyl optionally substituted with 1-3 Z5, or a bridged carbocylic ring substituted with 0-5 T1;
• each R9 is independently H or alkyl optionally substituted with 1-4 Z4;
• R10 is alkyl substituted with 0-4 Z4 and 0-1 Z7, —C0-C3alkyl-cycloalkyl optionally substituted with 1-4 Z3, —C0-C3alkyl-phenyl optionally substituted with 1-4 Z3, —C0-C3alkyl-heteroaryl optionally substituted with 1-3 Z5, or —C0-C3alkyl-heterocycloalkyl optionally substituted with 1-3 Z5;
• R11 is halogen, CN, —C(O)OH, —C(O)NH2, —C(O)N(H)heterocycloalkyl, or alkyl optionally substituted with halogen;
• each Z1 is independently halogen, alkyl, alkoxyl, —N(R5)(R6), or —C(O)OR5;
• Z2 is hydroxyl, halogen, or CN;
• each Z3 is independently alkyl, halogen, haloalkyl, hydroxyl, hydroxyalkyl, alkoxyl, haloalkoxyl, alkoxyalkyl, -haloalkyl-alkoxyalkyl, —C(O)OR9, or CN, provided that not more than 1 Z3 can be —C(O)OR9;
• each Z4 is independently hydroxyl, halogen, alkoxyl, —N(Ra)2, or CN;
• each Z5 is independently alkyl, haloalkyl, hydroxyl, hydroxyalkyl, halogen, alkoxyl, alkoxyalkyl, CN, cycloalkyl, or —C(O)OR9, provided that when Z5 is attached to a heteroatom, then Z5 is not halogen;
• hydroxyl, alkoxyl, CN, or —C(O)OR9;
• Z6 is —C(O)OH, —C(O)O-alkyl, —NH2, —N(H)alkyl, —N(alkyl)2, —C(O)NH2, —C(O)N(H)alkyl, —C(O)N(alkyl)2, —C(O)N(H)OH, heterocycloalkyl optionally substituted with 1-3 halogens, or phenyl optionally substituted with 1-3 halogens;
• and
• Z7 is —(CH2)0-2—N(R9)SO2—R7, —(CH2)0-2—SO2—R7, —(CH2)0-2—N(R9)SO2N(R8)R9, —(CH2)0-2—N(R9)C(O)N(R8)R9, —(CH2)0-2—N(R9)C(O)R8, —N(R9)C(O)OR9, —(CH2)0-2—N(R8)R9, —(CH2)0-2—C(O)—N(R8)R9, —C(O)OR9, —(CH2)0-2—C(O)R10, —(CH2)0-2—N(R9)C(O)R10, phenyl optionally substituted with 1-4 Z3, or heteroaryl optionally substituted with 1-3 Z5,
• provided that when L is —N(H)—C(O)—N(H)—, then R2 is not hydrogen or bromine;
• and
• provided that when L is —N(Ra)—C(O)—O—, then G is not an unsubstituted alkyl group.