4-cycloakylaminopyrazolo pyrimidine NMDA/NR2B antagonists

1. A compound having the formula (I):

wherein:

R 1 is selected from:

 unsubstituted or substituted with one or more substituents selected from: halogen, —R 2 , —O—R 2 , —CN, —N(R 2 ) 2 ,

Y is selected from:

 wherein the CH 2 moiety is bound to Z and the cyclopropyl moiety is bound to R 1 ,

 —R 3 — and —R 3 —O—R 3 —, where C′ and C″ are each independently directly or indirectly bound to an R 1 phenyl ring to form a 5 to 7 member fused ring;

Z is absent or is selected from O, C 1-6 alkylene, C 1-6 alkenylene, C(O), S, SO, SO 2 , NR 4 , where R 4 is hydrogen, C 0-6 alkyl or C 0-6 alkenyl, where said alkyl, alkenyl, alkylene or alkenylene is unsubstituted or is substituted with one or more substituents selected from: halogen, —R 5 , —O—R 5 , —CN, —N(R 5 ) 2 ;

A and B are each independently C 0-4 alkyl, where a ring is formed comprising A and B, where each member of said ring is independently unsubstituted or substituted with one or more substituents selected from halogen, —R 6 , —O—R 6 , —CN, —N(R 6 ) 2 ;

W is absent or is selected from O, C 0-6 alkylene, C 0-6 alkenylene, C(O), S, SO, SO 2 , NR 7 , where said alkyl, alkenyl, alkylene or alkenylene is unsubstituted or is substituted with one or more substituents selected from halogen, —R 8 , —O—R 8 , —CN, —N(R 8 ) 2 ;

 is unsubstituted or is substituted with one or more substituents selected from halogen, —R 9 , —O—R 9 , —CN, —N(R 9 ) 2 ;

R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are each independently hydrogen, C 0-6 alkyl, C 0-6 alkenyl unsubstituted or substituted with one or more halogen;

or a pharmaceutically acceptable salt thereof, or an individual diastereomer thereof.

2. A compound of claim 1 , wherein:

R 1 is

 unsubstituted or substituted with halogen or —R 2 , where R 2 is C 1-6 alkyl;

Y is —C 1-6 alkyl, independently unsubstituted or substituted with one or more halogen;

Z is O;

A and B are each independently C 0-4 alkyl;

W is absent;

or a pharmaceutically acceptable salt thereof or an enantiomer or diastereomer thereof.

3. A compound having the formula (Ia):

wherein:

R 1 is

 unsubstituted or substituted with halogen or —R 2 , where R 2 is C 1-6 alkyl, independently unsubstituted or substituted with one or more halogen;

Y is —C 1-6 alkyl, independently unsubstituted or substituted with one or more halogen;

or a pharmaceutically acceptable salt thereof or an enantiomer or diastereomer thereof.

4. A compound having the formula (Ib):

wherein:

R 1 is

 unsubstituted or substituted with halogen or —R 2 , where R 2 is C 1-6 alkyl, unsubstituted or substituted with one or more halogen;

the cyclopentyl group is unsubstituted or substituted with 1-3 fluorine;

Y is —C 1-6 alkyl, unsubstituted or substituted with one or more halogen;

or a pharmaceutically acceptable salt thereof or an enantiomer or diastereomer thereof.

5. A compound having the formula (Ic):

wherein:

R 1 is

 unsubstituted or substituted with halogen or —R 2 , where R 2 is C 1-6 alkyl, unsubstituted or substituted with one or more halogen;

R 4 is hydrogen or C 0-6 alkyl unsubstituted or substituted with one or more halogen;

the cyclopentyl group is unsubstituted or substituted with 1-3 fluorine;

Y is —C 1-6 alkyl, unsubstituted or substituted with one or more halogen;

or a pharmaceutically acceptable salt thereof or an enantiomer or diastereomer thereof.

6. A compound of claim 1 selected from:

or a pharmaceutically acceptable salt thereof, or an enantiomer or diastereomer thereof.

7. A pharmaceutical composition comprising an inert carrier and a therapeutically effective amount of a compound according to claim 1 .

8. The pharmaceutical composition according to claim 7 , further comprising a second therapeutic agent selected from the group consisting of: (i) non-steroidal anti-inflammatory agents; (ii) COX-2 inhibitors; (iii) bradykinin B1 receptor antagonists; (iv) sodium channel blockers and antagonists; (v) nitric oxide synthase (NOS) inhibitors; (vi) glycine site antagonists; (vii) potassium channel openers; (viii) AMPA/kainate receptor antagonists; (ix) calcium channel antagonists; (x) GABA-A receptor modulators (e.g., a GABA- A receptor agonist); (xi) matrix metalloprotease (MMP) inhibitors; (xii) thrombolytic agents; (xiii) opioids such as morphine; (xiv) neutrophil inhibitory factor (NIF); (xv) L-Dopa; (xvi) carbidopa; (xvii) levodopa/carbidopa; (xviii) dopamine agonists such as bromocriptine, pergolide, pramipexole, ropinirole; (xix) anticholinergics; (xx) amantadine; (xxi) carbidopa; (xxii) catechol O-methyltransferase (“COMT”) inhibitors such as entacapone and tolcapone; (xxiii) Monoamine oxidase B (“MAO-B”) inhibitors; (xiv) opiate agonists or antagonists; (xv) 5HT receptor agonists or antagonists; (xvi) NMDA receptor agonists or antagonists; (xvii) NK1 antagonists; (xviii) selective serotonin reuptake inhibitors (“SSRI”) and/or selective serotonin and norepinephrine reuptake inhibitors (“SSNRI”); (xxix) tricyclic antidepressant drugs, (xxx) norepinephrine modulators; (xxxi) lithium; (xxxii) valproate; and (xxxiii) neurontin (gabapentin).

9. A compound selected from

or a pharmaceutically acceptable salt thereof, or an enantiomer or diastereomer thereof.