2-aryl- and 2-heteroaryl-substituted 2-pyridazin-3(2H)-one compounds as inhibitors of FGFR tyrosine kinases

A compound of the general Formula I:

• and pharmaceutically acceptable salts thereof, wherein:
• X is N or CH;
• Ring A is a 5-membered heteroaryl ring having 1-2 ring nitrogen atoms;
• z is 1, 2 or 3;
• each R1 is independently selected from the group consisting of:
• (a) hydrogen;
• (b) C1-C6 alkyl optionally substituted with 1-3 fluoros,
• (c) hydroxy(C1-C6 alkyl)- optionally substituted with 1-3 fluoros,
• (d) dihydroxy(C1-C6 alkyl)- optionally substituted with 1-3 fluoros,
• (e) cyano(C1-C6 alkyl)-,
• (f) RaRbN(C1-C6 alkyl)-,
• (g) (C1-C3 alkoxy)C1-C6 alkyl- optionally substituted with 1-3 fluoros,
• (h) (C3-C6 cycloalkyl)(CH2)n— where n is 0-3 and said cycloalkyl is optionally substituted with CN, OH, RaRbN—, (1-3C)alkyl, or (1-3C)alkoxy;
• (i) hetCyc1(CH2)m— where m is 0-3,
• (j) hetCyc2(CH2)p— where p is 0 or 1,
• (k) hetAr1(CH2)q— where q is 1 or 2,
• (l) halogen, and
• (m) hetCyc1C(═O)CH2—;
• hetCyc1 is a 4-7 membered saturated heterocyclic ring having 1-2 ring heteroatoms independently selected from N and O, wherein said heterocyclic ring is optionally substituted with one or more substituents independently selected from the group consisting of fluoro, HO, C1-C6 alkyl (optionally substituted with 1-3 fluoros), (C1-C6 alkoxy)C1-C6 alkyl- (optionally substituted with 1-3 fluoros), (C3-C6 cycloalkoxy)C1-C6 alkyl-, hydroxy(C1-C6 alkyl)-, RcRdN- and (C1-C6 alkyl)C(═O)—;
• hetCyc2 is a 7-10 membered heterospirocyclic ring having 1-2 ring heteroatoms independently selected from N and O, wherein said heterospirocyclic ring is optionally substituted with one or more substituents independently selected from the group consisting of C1-C6 alkyl (optionally substituted with 1-3 fluoros), (C1-C6 alkoxy)C1-C6 alkyl- (optionally substituted with 1-3 fluoros), (C3-C6 cycloalkoxy)C1-C6 alkyl-, hydroxy(C1-C6 alkyl)-, RcRdN- and (C1-C6 alkyl)C(═O)—;
• hetAr1 is a 6-membered heteroaryl ring having 1-2 ring nitrogen atoms, wherein said ring is optionally substituted with one or more substituents independently selected from C1-C6 alkyl and halogen;
• R2 is AO or hetAr2;
• Ar1 is phenyl substituted with one or more groups independently selected from halogen, cyano, C1-C3 alkyl, C1-C3 alkoxy, (C1-C3 alkyl)NHC(═O)—, (C1-C3 alkyl)C(═O)NH—, (cyclopropyl)C(═O)NH— and (cyclopropyl)NHC(═O)—, wherein each of said C1-C3 alkyl and C1-C3 alkoxy portions is optionally substituted with 1-3 fluoros;
• hetAr2 is a 6-10 membered heteroaryl ring having 1-2 ring nitrogen atoms, wherein said ring is optionally substituted with one or more groups independently selected from halogen, C1-C3 alkyl, C1-C3 alkoxy, (C1-C3 alkyl)NHC(═O)—, (C1-C3 alkyl)C(═O)NH—, (C3-C4 cycloalkyl)C(═O)NH- and (C3-C4 cycloalkyl)NHC(═O)—, wherein each of said C1-C3 alkyl and C1-C3 alkoxy portions is optionally substituted with 1-3 fluoros;
• R3 is H, C1-C4 alkyl or (C3-C4)cycloalkyl;
• and
• Ra, Rb, Rc and Rd are independently hydrogen or C1-C6 alkyl optionally substituted with F, OH or C1-C6 alkoxy.