8-ethyl-6-(aryl)pyrido[2,3-D]pyrimidin-7(8H)-ones for the treatment of CNS disorders

1. A compound having the structure of Formula I or pharmaceutically acceptable salt or N-oxide thereof:

wherein:

R 7 is

wherein ring T is an aryl, or a heteroaryl ring;

R 3 is a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heteroaryl attached to ring T via a carbon atom of R 3 , or a substituted or unsubstituted heterocycloalkyl attached to ring T via a carbon atom of R 3 ;

Q is a substituted or unsubstituted alkyl, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted cycloalkylalkyl, a substituted or unsubstituted heterocycloalkylalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted arylalkyl, a substituted or unsubstituted heteroaryl, or a substituted or unsubstituted heteroarylalkyl;

each R 4 is independently halogen, —CN, —NO 2 , —OH, —OCF 3 , —OCH 2 F, —OCF 2 H, —CF 3 , —SR 8 , —NR 10 S(═O) 2 R 9 , —S(═O) 2 N(R 10 ) 2 , —C(═O)R 8 , —OC(═O)R 9 , —CO 2 R 10 , —N(R 10 ) 2 , —C(═O)N(R 10 ) 2 , —NR 10 C(═O)R 10 , —N R 10 C(═O)OR 10 , —NR 10 C(═O)N(R 10 ) 2 , a substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxy, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted heterocycloalkyl;

R 8 is H or R 9 ;

R 9 is a substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl;

each R 10 is independently H, a substituted or unsubstituted alkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; or two R 10 , together with the atoms to which they are attached form a heterocycle;

ring B is aryl or heteroaryl;

each R 5 is independently halogen, —CN, —NO 2 , —OH, —SR 8 , —S(═O)R 9 , —S(═O) 2 R 9 , NR 10 S(═O) 2 R 9 , —S(═O) 2 N(R 10 ) 2 , —C(═O)R 8 , —OC(═O)R 9 , —CO 2 R 10 , —N(R 10 ) 2 , —C(═O)N(R 10 ) 2 , —NR 10 C(═O)R 10 , —NR 10 C(═O)OR 10 , —NR 10 C(═O)N(R 10 ) 2 , —OR 10 , a substituted or unsubstituted alkyl, a substituted or unsubstituted alkoxy, a substituted or unsubstituted heteroalkyl, a substituted or unsubstituted cycloalkyl, or a substituted or unsubstituted heterocycloalkyl;

r is 0 to 8; and

s is 0 to 4.

2. The compound of claim 1 , wherein ring T is an aryl ring.

3. The compound of claim 1 , wherein ring T is a heteroaryl ring.

4. The compound of claim 1 , wherein ring T is selected from phenyl, pyrrole, furan, thiophene, pyrazole, imidazole, isoxazole, oxazole, isothiazole, thiazole, 1,2,3-triazole, 1,3,4-triazole, 1-oxa-2,3-diazole, 1-oxa-2,4-diazole, 1-oxa-2,5-diazole, 1-oxa-3,4-diazole, 1-thia-2,3-diazole, 1-thia-2,4-diazole, 1-thia-2,5-diazole, 1-thia-3,4-diazole, tetrazole, pyridine, pyridazine, pyrimidine, and pyrazine.

5. The compound of claim 1 having the structure of Formula V:

wherein s1 is 0 to 4.

6. The compound of claim 1 having the structure of Formula Va:

wherein s1 is 0 to 4.

7. The compound of claim 1 having the structure of Formula Vb:

8. The compound of claim 4 wherein R 3 is selected from pyrrole, furan, thiophene, pyrazole, imidazole, isoxazole, oxazole, isothiazole, thiazole, 1,2,3-triazole, 1,3,4-triazole, 1-oxa-2,3-diazole, 1-oxa-2,4-diazole, 1-oxa-2,5-diazole, 1-oxa-3,4-diazole, 1-thia-2,3-diazole, 1-thia-2,4-diazole, 1-thia-2,5-diazole, 1-thia-3,4-diazole, tetrazole, pyridine, pyridazine, pyrimidine, and pyrazine.

9. The compound of claim 8 , wherein

is

10. A compound selected from:

11. The compound of claim 9 , wherein the compound is a Group I p21-activated kinase inhibitor.

12. The compound of claim 9 , wherein the p21-activated kinase inhibitor causes substantially complete inhibition of one of more Group I p21-activated kinases.

13. The compound of claim 9 , wherein the p21-activated kinase inhibitor causes partial inhibition of one of more Group I p21-activated kinases.

14. The compound of claim 9 , the p21-activated kinase inhibitor modulates dendritic spine morphology or synaptic function.

15. The compound of claim 9 , wherein the p21-activated kinase inhibitor modulates dendritic spine density, dendritic spine length, dendritic spine neck diameter, and/or dendritic spine head diameter.