Gem-disubstituted and spirocyclic amino pyridines/pyrimidines as cell cycle inhibitors

1. A compound of Formula IA, IB, IC, or ID

or an enantiomer, diastereomer, or salt thereof wherein

t is 0;

v is 0, 1, 2, or 3;

R 1 is —Y—R a wherein

Y is selected from phenyl, pyridyl, pyrimidinyl, pyrazinyl, thiazolyl, or pyradizinyl any of which may be optionally independently substituted with one or more R x groups as allowed by valence; and

R a is selected from piperazinyl, piperidinyl, morpholinyl, or pyrrolidinyl any of which may be optionally substituted with one or more R x group as allowed by valence;

M is —CR d R e —, —O—, —S(O) n —, or —NHR 3 —;

R b , R c , R d and R e are each independently H or R x , or alternatively R b and R d on adjacent carbon ring atoms may optionally combine to form a double bond as allowed by valence, and R d and R e on adjacent carbon ring atoms may optionally combine to form a double bond as allowed by valence;

R 3 and R 4 at each occurrence are independently

(i) hydrogen or

(ii) alkyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl;

or R 3 and R 4 together with the nitrogen atom to which they are attached may combine to form a heterocyclo ring;

R 5 is

(i) hydrogen or

(ii) alkyl, alkenyl, alkynyl cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl;

R x at each occurrence is independently, halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, -(alkylene) m -OR 5 , -(alkylene) m -S(O) n R 5 , -(alkylene) m -NR 3 R 4 , -(alkylene) m -C(═O)R 5 , -(alkylene) m -C(═S)R 5 , -(alkylene) m -C(═O)OR 5 , -(alkylene) m -OC(═O)R 5 , -(alkylene) m -C(═S)OR 5 , -(alkylene) m -C(═O)NR 3 R 4 , -(alkylene) m -C(═S)NR 3 R 4 , -(alkylene) m -N(R 3 )C(═O)NR 3 R 4 , -(alkylene) m -N(R 3 )C(═S)NR 3 R 4 , -(alkylene) m -N(R 3 )C(═O)R 5 , -(alkylene) m -N(R 3 )C(═S)R 5 , -(alkylene) m -OC(═O)NR 3 R 4 , -(alkylene) m -OC(═S)NR 3 R 4 , -(alkylene) m -SO 2 NR 3 R 4 , -(alkylene) m -N(R 3 )SO 2 R 5 , -(alkylene) m -N(R 3 )SO 2 NR 3 R 4 , -(alkylene) m -N(R 3 )C(═O)OR 5 , -(alkylene) m -N(R 3 )C(═S)OR 5 , or -(alkylene) m -N(R 3 )SO 2 R 5 ;

n is 0, 1 or 2;

m is 0 or 1; and

p and q are independently 0, 1 or 2.

2. A compound of claim 1 wherein R 1 is selected from

3. The compound of claim 1 , wherein the compound has the Formula IA.

4. The compound of claim 3 wherein R 1 is selected from

5. The compound of claim 4 wherein R 1 is selected from

6. The compound of claim 3 wherein

is selected from

7. The compound of claim 1 , wherein the compound has the Formula IB.

8. The compound of claim 7 wherein R 1 is selected from

9. The compound of claim 8 wherein R 1 is selected from

10. The compound of claim 7 wherein

is selected from

11. The compound of claim 1 , wherein the compound has the Formula IC.

12. The compound of claim 11 wherein R 1 is selected from

13. The compound of claim 12 wherein R 1 is selected from

14. The compound of claim 11 wherein

is selected from

15. The compound of claim 1 , wherein the compound has the Formula ID.

16. The compound of claim 15 wherein R 1 is selected from

17. The compound of claim 16 wherein R 1 is selected from

18. The compound of claim 15 wherein

is selected from

19. A compound or a pharmaceutically acceptable salt thereof selected from

4,4-dimethyl-N-(5-(1-piperazinyl)-2-pyridinyl)spiro[cyclohex-2-ene-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

4,4-dimethyl-N-(4-(1-piperazinyl)phenyl)spiro[cyclohex-2-ene-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

N-(6-(4-(dimethylamino)-1-piperidinyl)-3-pyridinyl)-4,4-dimethylspiro[cyclohex-2-ene-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

4,4-dimethyl-N-(6-(4-methyl-1-piperazinyl)-3-pyridinyl)spiro[cyclohex-2-ene-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

N-(6-(1-piperazinyl)-3-pyridinyl)spiro[cyclohexane-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

N-(4-(1-piperazinylcarbonyl)-1,3-thiazol-2-yl)spiro[cyclohexane-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

N-(4-(1-piperazinyl)phenyl)spiro[indeno[2,1-d]pyrimidine-9,4′-piperidin]-2-amine;

N-(4-(1-piperidinyl)phenyl)spiro[indeno[2,1-d]pyrimidine-9,4′-piperidin]-2-amine;

N-(4-(4-morpholinyl)phenyl)spiro[indeno[2,1-d]pyrimidine-9,4′-piperidin]-2-amine;

1′-methyl-N-(4-(4-methyl-1-piperazinyl)phenyl)spiro[indeno[2,1-d]pyrimidine-9,4′-piperidin]-2-amine;

N-(4-(1-piperazinyl)phenyl)-2′,3′,5′,6′-tetrahydrospiro[indeno[2,1-d]pyrimidine-9,4′-pyran]-2-amine;

N-(4-(4-methyl-1-piperazinyl)phenyl)-2′,3′,5′,6′-tetrahydrospiro[indeno[2,1-d]pyrimidine-9,4′-pyran]-2-amine;

N-(3-fluoro-4-(4-methyl-1-piperazinyl)phenyl)-2′,3′,5′,6′-tetrahydrospiro[indeno[2,1-d]pyrimidine-9,4′-pyran]-2-amine;

tert-butyl 4-(4-(spiro[cyclohexane-1,9′-indeno[2,1-d]pyrimidin]-2′-ylamino)phenyl)-1-piperazinecarboxylate;

N-(4-(1-piperazinyl)phenyl)spiro[cyclohexane-1,9′-indeno[2,1-d]pyrimidin]-2′-amine;

N-(5-(1-piperazinyl)-2-pyridinyl)spiro[cyclopentane-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

9,9-diethyl-N-(5-(1-piperazinyl)-2-pyridinyl)-9H-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin-2-amine;

N-(5-(1-piperazinyl)-2-pyridinyl)-2,3,5,6-tetrahydrospiro[pyran-4,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

N-(5-(1-piperazinyl)-2-pyridinyl)spiro[cycloheptane-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

N-(5-(1-piperazinyl)-2-pyridinyl)spiro[cyclohexane-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

(3R)-1-(6-(spiro[cyclohexane-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-ylamino)-3-pyridazinyl)-3-pyrrolidinol;

4,4-dimethyl-N-(6-(4-(dimethylamino)piperidin-1-yl)-3-pyridinyl)spiro[cyclohex-2-ene-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine;

4,4-dimethyl-N-(6-(4-(dimethylamino)piperidin-1-yl)-pyridazin-3-yl)spiro[cyclohex-2-ene-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine; or

4,4-dimethyl-N-(6-(cis-3,5-dimethylpiperazin-1-yl)pyridin-3-yl)spiro[cyclohex-2-ene-1,9′-pyrido[4′,3′:3,4]cyclopenta[1,2-d]pyrimidin]-2′-amine.

20. A pharmaceutical composition comprising the compound of claim 1 together with a pharmaceutically acceptable vehicle, adjuvant or diluent.