Macrocyclic compounds as Trk kinase inhibitors

A compound of the general Formula I

• or pharmaceutically acceptable salts thereof, wherein:
• ring A is selected from rings A-1, A-2 and A-3 having the structures:
• wherein the wavy line labeled 1 indicates the point of attachment of ring A to ring B and the wavy line labeled 2 indicates the point of attachment of ring A to W;
• X is N or CH;
• Y is H or F;
• R1 is H, (1-3C)alkoxy or halogen;
• ring B is B-1
• wherein the wavy line labeled 3 indicates the point of attachment to ring A and the wavy line labeled 4 indicates the point of attachment to the pyrazolo[1,5-a]pyrimidine ring of Formula I;
• W is O, NH or CH2, wherein when ring A is A-2, then W is CH2;
• m is 0, 1 or 2;
• D is carbon, R2 and R2a are independently H, F, (1-3 C)alkyl or OH (provided that R2 and R2a are not both OH), and R3 and R3′ are independently H, (1-3 C)alkyl or hydroxy(l-3 C)alkyl, or
• D is carbon or nitrogen, R2 and R3 are absent, and R2a and R3a together with the atoms to which they are attached form a 5-6 membered heteroaryl ring having 1-2 ring heteroatoms;
• Z is *—NR4aC(═O)—, *—ONHC(═O)—, *—NR4bCH2— or *—OC(═O)—, wherein the asterisk indicates the point of attachment of Z to the carbon bearing R3;
• R4a is H, (1-6C)alkyl, fluoro(1-6C)alkyl, difluoro(1-6C)alkyl, trifluoro(1-6C)alkyl, hydroxy(l-6C alkyl) or dihydroxy(2-6C alkyl);
• R4b is H, (1-6C)alkyl, fluoro(1-6C)alkyl, difluoro(1-6C)alkyl, trifluoro(1-6C)alkyl, hydroxy(l-6C alkyl), dihydroxy(2-6C alkyl), (1-6C alkyl)C(O)—, (3-6C cycloalkyl)C(O)—, Ar1C(O)—, HO CH2C(O)—, (1-6C alkyl)sulfonyl, (3-6C cycloalkyl)sulfonyl, Ar2(SO2)—, HO2CCH2— or (1-6C alkyl)NH(CO)—;
• Ar1 is phenyl optionally substituted with one or more substituents independently selected from halogen, (1-6C)alkyl, and (1-6C)alkoxy;
• Ar2 is phenyl optionally substituted with one or more substituents independently selected from halogen, (1-6C)alkyl, and (1-6C)alkoxy;
• and
• R5 and R6 are independently H, halogen, OH, (1-6C)alkyl or hydroxy(l-6C)alkyl.