Macrocyclic compounds as TRK kinase inhibitors

1. A compound of the general Formula II

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;

R 1 is H, (1-3C)alkoxy or halogen;

ring B is selected from rings B-1 and B-2 having the structures:

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 II;

W is O, NH or CH 2 , wherein when ring A is A-2, then W is CH 2 ;

m is 0, 1 or 2;

D is carbon, R 2 and R 2a are independently H, F, (1-3 C)alkyl or OH (provided that R 2 and R 2a are not both OH), and R 3 and R 3a are independently H, (1-3 C)alkyl or hydroxy(1-3 C)alkyl, or

D is carbon or nitrogen, R 2 and R 3 are absent, and R 2a and R 3a together with the atoms to which they are attached form a 5-6 membered heteroaryl ring having 1-2 ring heteroatoms;

P 1 is H or a carboxyl protecting group; and

R 5 and R 6 are independently H, halogen, OH, (1-6C)alkyl or hydroxy(1-6C)alkyl.

2. A compound according to claim 1 , wherein D is carbon, R 2 and R 2a are independently H, F, (1-3 C)alkyl or OH (provided that R 2 and R 2a are not both OH), and R 3 and R 3a are independently H, (1-3 C)alkyl or hydroxy(1-3 C)alkyl.

3. A compound according to claim 1 , wherein:

R 3 and R 3a are H; or

R 3a is methyl and R 3 is H; or

R 3a and R 3 are both methyl.

4. A compound according to claim 1 , wherein ring B is ring B-1:

 and

R 5 and R 6 are independently H, F, OH, methyl, ethyl, HOCH 2 — or HOCH 2 CH 2 —.

5. A compound according to claim 4 , wherein R 5 is hydrogen and R 6 is H, F, OH, methyl, ethyl, HOCH 2 — or HOCH 2 CH 2 —.