SUBSTITUTED PYRAZOLO[3,4-d]PYRIMIDINE COMPOUNDS AS RET KINASE INHIBITORS

A compound of Formula I:

• and pharmaceutically acceptable salts thereof, wherein:
• R1 is a 5-membered heteroaryl ring having 2-3 ring heteroatoms independently selected from N, O and S, wherein R1 is optionally substituted with 1-3 substituents independently selected from halogen, C1-C6 alkyl, fluoroC1-C6 alkyl, hydroxyC1-C6 alkyl, (C1-C6 alkoxy)C1-C6 alkyl-, C2-C6 alkenyl, Cyc1, hetCyc1, Ar1, hetAr1, (C1-C6 alkyl)C(═O)—, (C1-C6 alkyl)2-P(═O)—, and R′R″NC(═O)— wherein R′ is hydrogen and R″ is hydrogen, C1-C alkyl or Cyc2,
• provided that when R1 is an isoxazolyl ring, then R1 is substituted with 2 substituents independently selected from halogen, C1-C6 alkyl, fluoroC1-C6 alkyl, hydroxyC1-C6 alkyl, (C1-C6 alkoxy)C1-C6 alkyl-, C2-C6 alkenyl, Cyc1, hetCyc1, Ar1, hetAr1, (C1-C6 alkyl)C(═O)—, (C1-C6 alkyl)2-P(═O)—, and R′R″NC(═O)— wherein R′ is hydrogen and R″ is hydrogen, C1-C alkyl or Cyc2;
• Cyc1 is a 3-6 membered saturated or partially unsaturated cycloalkyl ring optionally substituted with one or more substituents independently selected from hydroxy, C1-C6 alkyl and oxo;
• hetCyc1 is a 4-6 membered saturated or partially unsaturated heterocyclic ring having 1-2 ring heteroatoms independently selected from N and O and optionally substituted with one or more substituents independently selected from C1-C6 alkyl, hydroxy, and oxo;
• Ar1 is phenyl optionally substituted with one or more substituents independently selected from C1-C6 alkyl, fluoroC1-C6 alkyl, halogen, and hydroxy;
• Cyc2 is C3-C6 cycloalkyl optionally substituted with hydroxy;
• hetAr1 is a 5-6 membered heteroaryl ring having 1-3 ring nitrogen atoms and optionally substituted with one or more substituents independently selected from C1-C6 alkyl, fluoroC1-C6 alkyl, halogen, hydroxy, and benzyl;
• and
• R2 is hydrogen, C1-C6 alkyl, fluoroC1-C6 alkyl, cyanoC1-C6 alkyl-, hydroxyC1-C6 alkyl, C3-C6 cycloalkyl or (C3-C6 cycloalkyl)C1-C6 alkyl-.