PYRIMIDINE-BASED ANTIPROLIFERATIVE AGENTS

1 . A compound of Formula:

or a pharmaceutically acceptable salt thereof,

wherein:

y is 0, 1, 2, 3 or 4;

R is hydrogen or C 1 -C 6 alkyl;

each R 1 is independently alkyl, aryl, cycloalkyl or haloalkyl, wherein each of said alkyl, cycloalkyl and haloalkyl groups optionally includes heteroatoms O, N, or S in place of a carbon in the chain and two R 1 s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle;

R 2 is -(alkylene) m -heterocyclo, -(alkylene) m -heteroaryl, -(alkylene) m -NR 3 R 4 , -(alkylene) m -C(O)—NR 3 R 4 ; -(alkylene) m -C(O)—O-alkyl; -(alkylene) m -O—R 5 , -(alkylene) m -S(O) n —R 5 , or -(alkylene) m -S(O) n —NR 3 R 4 any of which may be optionally independently substituted with one or more R x groups as allowed by valance, and wherein two R x groups bound to the same or adjacent atom may optionally combine to form a ring;

m is 0, 1, or 2;

n is 0, 1, or 2;

R 3 and R 4 at each occurrence are independently selected from:

(i) hydrogen or

(ii) alkyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, and 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 selected from:

(i) hydrogen or

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

R x at each occurrence is independently selected from halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, heterocycloalkyl, -(alkylene) m -OR 5 , -(alkylene) m -O-alkylene-OR 5 , -(alkylene) m -S(O)—R 5 , -(alkylene) m -NR 3 R 4 , -(alkylene) m -CN, -(alkylene) m -C(O)—R 5 , -(alkylene) m -C(S)—R 5 , -(alkylene) m -C(O)—OR 5 , -(alkylene) m -O—C(O)—R 5 , -(alkylene) m -C(S)—OR 5 , -(alkylene) m -C(O)-(alkylene) m -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 -O—C(O)—NR 3 R 4 , -(alkylene) m -O—C(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 ;

R 6 is selected independently at each instance from: hydrogen, halogen, alkyl, alkenyl, alkynyl cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl;

R 7 is selected from:

or R 7 is selected from cycloalkyl, heterocycle, and alkyl, each of which cycloalkyl, heterocycle, and alkyl groups is optionally substituted with one or more substituents selected from amino, —NHR 14 , —NR 14 R 15 , hydroxyl, OR 14 , R 6 , and R 2 ;

R 14 and R 15 are independently selected from: hydrogen, alkyl, alkenyl, alkynyl, —C(O)H, —C(O)alkyl, —C(S)alkyl, aryl, —SO 2 alkyl, heteroaryl, arylalkyl, and heteroarylalkyl.

Y is NH, O, S, or NR 9 ;

X 1 , X 2 , X 3 and X 4 are independently N or CR, wherein at least one of X 1 , X 2 , X 3 , X 4 , and X 5 are CR;

R 8 is selected independently at each instance from: R 6 and R 2 , wherein one R 8 is R 2 ; and

R 9 is selected from: —C(O)H, —C(O)alkyl, —C(S)alkyl, alkyl, aryl, heteroaryl, arylalkyl, and heteroarylalkyl.

2 . The compound of claim 1 of Formula

or a pharmaceutically acceptable salt thereof.

3 . The compound of claim 1 , wherein X 1 and X 2 are CH.

4 . The compound of claim 1 of Formula

or a pharmaceutically acceptable salt thereof.

5 . The compound of claim 1 , wherein at least one R 1 is alkyl.

6 . The compound of claim 1 , wherein two R 1 s on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached form a 3-8-membered cycle.

7 . The compound of claim 1 , wherein two R 1 s on the same ring atom together with the ring atom to which they are attached form cyclohexyl.

8 . The compound of claim 1 , wherein y is 2.

9 . The compound of claim 1 , wherein y is 3.

10 . The compound of claim 1 of Formula

or a pharmaceutically acceptable salt thereof.

11 . The compound of claim 1 , wherein R is H.

12 . The compound of claim 1 , wherein R is methyl or ethyl.

13 . The compound of claim 1 of Formula

or a pharmaceutically acceptable salt thereof.

14 . The compound of claim 1 , wherein, R 2 is -(alkylene) m -S(O)—NR 3 R 4 .

15 . The compound of claim 14 , wherein n is 2.

16 . The compound of claim 1 , wherein, R 2 is -(alkylene) m -S(O)—NR 3 R 4 .

17 . The compound of claim 1 , wherein R 2 is -(alkylene) m -heterocyclo optionally independently substituted with one or more R x groups as allowed by valance.

18 . The compound of claim 1 , wherein R 2 is selected from:

19 . The compound of claim 1 , wherein R 2 is selected from:

20 . The compound of claim 1 , wherein the compound is selected from

or a pharmaceutically acceptable salt thereof.

21 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

22 . A method for the treatment of a disorder associated with abnormal cellular proliferation comprising administering an effective amount to a host in need thereof of a compound of claim 1 , or a pharmaceutically acceptable salt thereof optionally in a pharmaceutically acceptable carrier.

23 . The method of claim 22 , wherein the host is a human.