HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF ABNORMAL CELLULAR PROLIFERATION

1 . A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof,

wherein:

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

X is S, CH 2 , CHR 12 , CR 12 R 13 , NH, or NR 12 ;

Z is independently O, S, CH 2 , CHR 12 , CR 12 R 13 , NH, or NR 12 ;

Q is CH or N;

represents the presence or absence of a double bond;

each R is independently hydrogen, C 1 -C 6 alkyl, —(C 0 -C 2 alkyl)(C 3 -C 6 cycloalkyl), —(C 0 -C 2 alkyl)(C 3 -C 8 heterocycle), —(C 0 -C 2 alkyl)(aryl), —(C 0 -C 2 alkyl)(heteroaryl), —COOalkyl, —COOalkyl-aryl, or —COOH;

each R 1 is independently hydrogen, alkyl, aryl, cycloalkyl, haloalkyl, heteroaryl, or heterocycle; wherein two R 1 groups on adjacent ring atom(s) or on the same ring atom may come together with the ring atom(s) to which they are attached to optionally constitute a 3, 4, 5, 6, 7, or 8-membered cycloalkyl or heterocycle that has 1, 2, or 3 heteroatoms selected from N, O, and S; wherein the 3, 4, 5, 6, 7, or 8-membered cycloalkyl or heterocycle formed by combining two R 1 s with the atom(s) to which they are attached can be optionally substituted with 1, 2, 3, or 4 substituents independently selected from R 50 ;

R 50 is selected from the group consisting of hydrogen, amino, —NHR 14 , —NR 14 R 15 , hydroxyl, OR 14 , R 6 , and R 2 ;

R 7 is selected from the group consisting of aryl, heteroaryl, cycloalkyl, heterocycle, alkyl, —C(O)aryl, —C(O)heteroaryl, —C(O)cycloalkyl, —C(O)heterocycle, —C(O)alkyl, and —C(O)heterocycle; each of which R 7 is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of amino, halogen, alkyl, —NHR 14 , —NR 14 R 15 , hydroxyl, OR 14 , R 6 , and R 2 ;

R 2 is independently selected from the group consisting of -(alkylene) m -heterocycle, -(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 , and -(alkylene) m -S(O) n —NR 3 R 4 ; any of which may be optionally independently substituted with 1, 2, 3, or 4 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 or 1;

n is independently 0, 1, or 2;

R 3 and R 4 at each occurrence are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocycle, aryl, heteroaryl, alkyl-cycloalkyl, alkyl-heterocycle, alkyl-aryl, and alkyl-heteroaryl; each of which R 3 and R 4 except hydrogen may be optionally independently substituted with 1, 2, 3, or 4 R x groups as allowed by valance; or

R 3 and R 4 together with the nitrogen atom to which they are attached may combine to form a heterocycle ring optionally independently substituted with 1, 2, 3, or 4 R x groups as allowed by valance, and wherein two R x s bound to the same or adjacent atom(s) may optionally combine to form a 3, 4, 5, 6, 7, or 8-membered cycloalkyl or heterocycle that has 1, 2, or 3 heteroatoms selected from N, O, and S;

R 5 is independently selected at each occurrence from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycle, aryl, heteroaryl, alkyl-cycloalkyl, alkyl-heterocycle, alkyl-aryl, and alkyl-heteroaryl; each of which R 5 except hydrogen may be optionally independently substituted with 1, 2, 3, or 4 R x groups as allowed by valance;

R x at each occurrence is independently selected from the group consisting of hydroxy, —O-alkyl, halogen, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocycle, aryl, heteroaryl, alkyl-aryl, alkyl-heteroaryl, alkyl-cycloalkyl, amino, —C(O)N(R 6 ) 2 , —C(O)OR 6 , and alkyl-heterocycle; each of which R x groups except halogen, cyano, nitro, and oxo may be further independently substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of hydroxy, —O-alkyl, halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocycle, aryl, heteroaryl, alkyl-aryl, alkyl-heteroaryl, alkyl-cycloalkyl, and alkyl-heterocycle; or

R x is selected from the group consisting of —C(O)alkyl and —C(O)cycloalkyl;

R 6 is selected independently at each instance from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, heterocycle, aryl, heteroaryl, alkyl-cycloalkyl, alkyl-heterocycle, alkyl-aryl, and alkyl-heteroaryl;

R 10 and R 11 are independently selected from the group consisting of hydrogen, alkyl, —NH 2 , —NHR 12 , —NR 12 R 13 , —S(O)alkyl, —SO 2 alkyl, cycloalkyl, heterocycle, aryl, heteroaryl, alkyl-aryl, and alkyl-heteroaryl; each of which R 10 and R 11 except hydrogen is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of amino, —NHR 14 , —NR 14 R 15 , hydroxyl, OR 14 , R 6 , and R 2 ;

R 12 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, —C(O)R 6 , —C(O)alkyl, —C(S)alkyl, aryl, —SO 2 alkyl, heteroaryl, alkyl-aryl, cycloalkyl, heterocycle, and alkyl-heteroaryl; each of which R 12 except hydrogen is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of amino, —NHR 14 , —NR 14 R 15 , hydroxyl, OR 14 , R 6 , and R 2 ;

R 13 is independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, —C(O)R 6 , —C(O)alkyl, —C(S)alkyl, aryl, —SO 2 alkyl, heteroaryl, alkyl-aryl, cycloalkyl, heterocycle, and alkyl-heteroaryl; each of which R 13 except hydrogen is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of amino, —NHR 14 , —NR 14 R 15 , hydroxyl, OR 14 , R 6 , and R 2 ;

R 14 and R 15 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, —C(O)R 6 , —C(O)alkyl, —C(S)alkyl, aryl, —SO 2 alkyl, heteroaryl, heterocycle, alkyl-aryl, and alkyl-heteroaryl;

R 16 is cycloalkyl substituted with at least one substituent selected from R 17 and optionally substituted with 1, 2, 3, or 4 substituents independently selected from R x ; or

R 16 is cycloalkyl-heterocycle-R x optionally substituted with 1, 2, 3, or 4 additional substituents independently selected from R x ;

R 17 is independently selected from the group consisting of —NR—S(O)alkyl, —NR—S(O) 2 alkyl, —NR-heterocycle, —NR-heteroaryl, —NR-aryl, —NR-alkyl-heteroaryl, and —NR-alkyl-aryl, each of which R 17 is optionally substituted with 1, 2, 3, or 4 substituents selected from the group consisting of R x ;

R 19 is a heterocycle substituted with at least one substituent independently selected from the group consisting of amino, halogen, alkyl, —NHR 14 , —NR 14 R 15 , hydroxyl, OR 14 , R 6 , oxo, and R 2 ;

R 20 is selected from the group consisting of —C(O)alkyl, —C(O)aryl, —C(O)heteroaryl, —C(O)cycloalkyl, and —C(O)heterocycle; each of which R 20 is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of amino, halogen, alkyl, —NHR 14 , —NR 14 R 15 hydroxyl, OR 14 , R 6 , —C(O)R 6 , and R 2 ;

R 21 is selected from the group consisting of

and

R 22 is selected from the group consisting of

2 . The compound of claim 1 wherein R is hydrogen.

3 . The compound of claim 2 , wherein the compound is of formula:

or a pharmaceutically acceptable salt thereof.

4 . The compound of claim 3 , wherein R 7 is selected from the group consisting of:

5 . The compound of claim 4 , wherein n is 0.

6 . The compound of claim 5 , wherein Q is CH.

7 . The compound of claim 2 , wherein the compound is of formula:

or a pharmaceutically acceptable salt thereof.

8 . The compound of claim 7 , wherein R 21 is

9 . The compound of claim 2 , wherein the compound is of formula:

or a pharmaceutically acceptable salt thereof.

10 . The compound of claim 9 , wherein R 22 is

11 . The compound of claim 9 , wherein R 22 is

12 . The compound of claim 9 , wherein R 22 is

13 . The compound claim 1 , wherein R 1 is hydrogen, alkyl, or aryl.

14 . The compound claim 1 , wherein y is 0, 1, or 2.

15 . The compound of claim 1 , wherein two R 1 groups on the same ring atom come together with the ring atom to which they are attached to constitute a 3, 4, 5, 6, 7, or 8-membered cycloalkyl or heterocycle that has 1, 2, or 3 heteroatoms selected from N, O, and S.

16 . The compound of claim 1 , wherein two R 1 groups on the same ring atom come together with the ring atom to which they are attached to constitute a 6-membered cycloalkyl.

17 . The compound of claim 1 selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

18 . The compound of claim 1 selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

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

20 . A method for reducing the effect of chemotherapy on healthy cells in a human being treated for cancer or abnormal cell proliferation comprising administering an effective amount of a compound of claim 1 to a host in need thereof, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.

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