Macrocyclic compounds as TRK kinase inhibitors

A method for attenuating or ameliorating one or more symptoms of a cancerous tumor in a mammal in need thereof, the method comprising:

• (a) detecting a cancerous tumor in a mammal that exhibits one or more of overexpression, activation, amplification, and mutation of a Trk kinase;
• and
• (b) administering to the mammal a therapeutically effective amount of a compound of Formula (I)
• or a pharmaceutically acceptable salt thereof, wherein:
• ring A is ring A-1 having the structure:
• 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;
• Y is H or F;
• R1 is H, (1-3C)alkyl, (1-3C)alkoxy or halogen;
• 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, (1-3C)alkyl or OH (provided that R2 and R2a are not both OH), and R3 and R3a are independently H, (1-3C)alkyl or hydroxy(1-3 C)alkyl;
• Z is *—NR4aC(═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(1-6C alkyl) or dihydroxy(2-6C alkyl);
• and
• R5 and R6 are independently H, halogen, OH, (1-6C)alkyl or hydroxy(1-6C)alkyl.