Cyclic di-nucleotide compounds as sting agonists

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein

Base 1 and Base 2 are each independently selected from the group consisting of

where Base 1 and Base 2 each may be independently substituted by 0-3 substituents R 10 , where each R 10 is independently selected from the group consisting of F, Cl, I, Br, OH, SH, NH 2 , C 1-3 alkyl, C 3-6 cycloalkyl, O(C 1-3 alkyl), O(C 3-6 cycloalkyl), S(C 1-3 alkyl), S(C 3-6 cycloalkyl), NH(C 1-3 alkyl), NH(C 3-6 cycloalkyl), N(C 1-3 alkyl) 2 , and N(C 3-6 cycloalkyl) 2 ;

Y and Y a are each independently selected from the group consisting of —O—, —S—, —SO 2 —, —CH 2 —, and —CF 2 —;

X a and X a1 are each independently selected from the group consisting of —O—, —S—, and —CH 2 —;

X b and X b1 are each independently selected from the group consisting of —O—, —S—, and —CH 2 —;

X c and X c1 are each independently selected from the group consisting of SR 9 , OR 9 , and NR 9 R 9 ;

X d and X d1 are each independently selected from the group consisting of O and S;

R 1 and R 1a are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl, where said R 2 and R 2a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

R 2 and R 2a are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl, where said R 2 and R 2a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

R 3 is selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl, where said R 3 C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

R 4 and R 4a are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl, where said R 4 and R 4a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

R 5 is selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl, where said R 5 C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

R 6 and R 6a are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl, where said R 6 and R 6a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

R 7 and R 7a are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl, where said R 7 and R 7a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

R 8 and R 8a are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl, where said R 8 and R 8a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 haloalkyl, C 2 -C 6 haloalkenyl, C 2 -C 6 haloalkynyl, —O—C 1 -C 6 alkyl, —O—C 2 -C 6 alkenyl, and —O—C 2 -C 6 alkynyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

each R 9 is independently selected from the group consisting of H, C 1 -C 20 alkyl,

where each R 9 C 1 -C 20 alkyl is optionally substituted by 0 to 3 substituents independently selected from the group consisting of OH, —O—C 1 -C 20 alkyl, —S—C(O)C 1 -C 6 alkyl, and C(O)OC 1 -C 6 alkyl;

optionally R 1a and R 3 are connected to form C 1 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 1a and R 3 are connected to form —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, said 0 is bound at the R 3 position;

optionally R 2a and R 3 are connected to form C 1 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 2a and R 3 are connected to form —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, said O is bound at the R 3 position;

optionally R 3 and R 6a are connected to form C 1 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 3 and R 6a are connected to form —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, said O is bound at the R 3 position;

optionally R 4 and R 5 are connected to form C 1 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 4 and R 5 are connected to form —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, said O is bound at the R 5 position;

optionally R 5 and R 6 are connected to form —O—C 1 -C 6 alkylene, —O—C 2 -C 6 alkenylene, or —O—C 2 -C 6 alkynylene, such that where R 5 and R 6 are connected to form —O—C 1 -C 6 alkylene, —O—C 2 -C 6 alkenylene, or —O—C 2 -C 6 alkynylene, said O is bound at the R 5 position;

optionally R 7 and R 8 are connected to form C 1 -C 6 alkylene or C 2 -C 6 alkenylene; and

optionally R 7a and R 8a are connected to form C 1 -C 6 alkylene or C 2 -C 6 alkenylene; and

provided that at least one of

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein

Base 1 and Base 2 are each independently selected from the group consisting of

where Base 1 and Base 2 each may be independently substituted by 0-3 substituents R 10 , where each R 10 is independently selected from the group consisting of F, Cl, I, Br, OH, SH, NH 2 , C 1-3 alkyl, C 3-6 cycloalkyl, O(C 1-3 alkyl), O(C 3-6 cycloalkyl), S(C 1-3 alkyl), S(C 3-6 cycloalkyl), NH(C 1-3 alkyl), NH(C 3-6 cycloalkyl), N(C 1-3 alkyl) 2 , and N(C 3-6 cycloalkyl) 2 ;

Y and Y a are each independently selected from the group consisting of —O— and —S—;

X a and X a1 are each independently selected from the group consisting of O and S;

X b and X b1 are each independently selected from the group consisting of O and S;

X c and X c1 are each independently selected from the group consisting of SR 9 , OR 9 , and NR 9 R 9 ;

X d and X d1 are each independently selected from the group consisting of O and S;

R 1 and R 1a are each H;

R 2 and R 2a are each independently selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl, where said R 2 and R 2a C 1 -C 6 alkyl or C 1 -C 6 haloalkyl are substituted by 0 to 3 substituents selected from the group consisting of OH, CN, and N 3 ;

R 3 is selected from the group consisting of H, F, Cl, Br, I, OH, CN, N 3 , C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl, where said R 3 C 1 -C 6 alkyl or C 1 -C 6 haloalkyl are substituted by 0 to 3 substituents selected from the group consisting of OH, CN, and N 3 ;

R 4 and R 4a are each independently selected from the group consisting of H, F, Cl, I, Br, CN, OH, N 3 , C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl, where said R 4 and R 4a C 1 -C 6 alkyl or C 1 -C 6 haloalkyl are substituted by 0 to 3 substituents selected from the group consisting of OH, CN, and N 3 ;

R 5 is selected from the group consisting of H, F, Cl, Br, I, OH, N 3 , C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl, where said R 5 C 1 -C 6 alkyl or C 1 -C 6 haloalkyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

R 6 and R 6a are each independently selected from the group consisting of H, F, Cl, I, Br, OH, CN, N 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl, where said R 6 and R 6a C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl are substituted by 0 to 3 substituents selected from the group consisting of F, Cl, Br, I, OH, CN, and N 3 ;

R 7 and R 7a are each independently selected from the group consisting of H, C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl, where said R 7 and R 7a C 1 -C 6 alkyl or C 1 -C 6 haloalkyl are substituted by 0 to 3 substituents selected from the group consisting of OH, CN, and N 3 ;

R 8 and R 8a are each independently selected from the group consisting of H, C 1 -C 6 alkyl, and C 1 -C 6 haloalkyl, where said R 8 and R 8a C 1 -C 6 alkyl or C 1 -C 6 haloalkyl are substituted by 0 to 3 substituents selected from the group consisting of OH, CN, and N 3 ;

each R 9 is independently selected from the group consisting of H, C 1 -C 6 alkyl,

where each R 9 C 1 -C 6 alkyl is optionally substituted by 1 to 2 substituents independently selected from the group consisting of OH, —O—C 1 -C 20 alkyl,—S—C(O)C 1 -C 6 alkyl, and —C(O)OC 1 -C 6 alkyl;

optionally R 3 and R 6a are connected to form C 2 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 3 and R 6a are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, said O is bound at the R 3 position; and

optionally R 5 and R 6 are connected to form C 1 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 5 and R 6 are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, said O is bound at the R 5 position.

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein

Base 1 and Base 2 are each independently selected from the group consisting of

Y and Y a are each independently selected from the group consisting of —O— and —S—;

X a and X a1 are each independently selected from the group consisting of O and S;

X b and X b1 are each independently selected from the group consisting of O and S;

X c and X c1 are each independently selected from the group consisting of —OH, —SH,

X d and X d1 are each independently selected from the group consisting of O and S;

R 1 and R 1a are each H;

R 2 and R 2a are each independently selected from the group consisting of H, F, Cl, I, Br, OH, CN, N 3 , CF 3 , CH 3 , CH 2 OH, and CH 2 CH 3 ;

R 3 is selected from the group consisting of H, F, Cl, I, Br, OH, CN, N 3 , CF 3 , CH 3 , CH 2 OH, and CH 2 CH 3 ;

R 4 and R 4a are each independently selected from the group consisting of H, F, Cl, I, Br, OH, CN, N 3 , CF 3 , CH 3 , CH 2 OH, and CH 2 CH 3 ;

R 5 is selected from the group consisting of H, F, Cl, I, Br, OH, CN, N 3 , CF 3 , CH 3 , CH 2 OH, and CH 2 CH 3 ;

R 6 and R 6a are each independently selected from the group consisting of H, F, Cl, I, Br, OH, CN, N 3 , CF 3 , CH 3 , CH 2 OH, CH 2 CH 3 , —CH═CH 2 , —C═CH, and —C═C—CH;

R 7 and R 7a are each independently selected from the group consisting of H, CF 3 , CH 3 , and CH 2 CH 3 ;

R 8 and R 8a are each independently selected from the group consisting of H, CF 3 , CH 3 , and CH 2 CH 3 ;

optionally R 3 and R 6a are connected to C 2 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 3 and R 6a are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, said O is bound at the R 3 position; and

optionally R 5 and R 6 are connected to form C 1 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 5 and R 6 are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, said O is bound at the R 5 position.

4. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein

Base 1 and Base 2 are each independently selected from the group consisting of

Y and Y a are each independently selected from the group consisting of —O— and —S—;

X a and X a1 are each O;

X b and X b1 are each O;

X c and X c1 are each independently selected from the group consisting of —OH and —SH;

X d and X d1 are each independently selected from the group consisting of O and S;

R 1 and R 1a are each H;

R 2 and R 2a are each independently selected from the group consisting of H, F, Cl, OH, CN, N 3 , and CH 3 ;

R 3 is selected from the group consisting of H, F, Cl, OH, CN, N 3 , and CH 3 ;

R 4 and R 4a are each independently selected from the group consisting of H, F, Cl, OH, CN, N 3 , and CH 3 ;

R 5 is selected from the group consisting of H, F, Cl, OH, CN, N 3 , and CH 3 ;

R 6 and R 6a are each independently selected from the group consisting of H, F, CN, N 3 , CH 3 , —CH═CH 2 , and —C═CH;

R 7 and R 7a are each H;

R 8 and R 8a are each H;

optionally R 3 and R 6a are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, such that O is bound at the R 3 position; and

optionally R 5 and R 6 are connected to form C 1 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 5 and R 6 are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, said O is bound at the R 5 position.

5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein

Base 1 and Base 2 are each independently selected from the group consisting of

Y and Y a are each independently selected from the group consisting of —O— and —S—;

X a and X a1 are each O;

X b and X b1 are each O;

X c and X c1 are each independently selected from the group consisting of —OH and —SH;

X d and X d1 are each independently selected from the group consisting of O and S;

R 1 and R 1a are each H;

R 2 and R 2a a are each independently selected from the group consisting of H, F, Cl, OH, CN, N 3 , and CH 3 ;

R 3 is selected from the group consisting of H, F, Cl, OH, CN, N 3 , and CH 3 ;

R 4 and R 6a are each independently selected from the group consisting of H, F, Cl, OH, CN, N 3 , and CH 3 ;

R 5 is selected from the group consisting of H, F, Cl, OH, CN, N 3 , and CH 3 ;

R 6 and R 6a a are each independently selected from the group consisting of H, F, CN, N 3 , CH 3 , —CH═CH 2 , and —C═CH;

R 7 and R 7a a are each H;

R 8 and R 8a are each H;

optionally R 3 and R 6a are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, such that where R 3 and R 6a are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, said O is bound at the R 3 position; and

optionally R 5 and R 6 are connected to form C 1 -C 6 alkylene, C 2 -C 6 alkenylene, —O—C 1 -C 6 alkylene, or —O—C 2 -C 6 alkenylene, such that where R 5 and R 6 are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, said O is bound at the R 5 position.

6. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein

Base 1 and Base 2 are each independently selected from the group consisting of

Y and Y a are each independently selected from the group consisting of —O— and —S—; X a and X a1 are each O;

X b and X b1 are each O;

X c and X c1 are each independently selected from the group consisting of SH and OH;

X d and X d1 are each independently selected from the group consisting of O and S;

R 1 and R 1a are each H;

R 2 and R 2a are each independently selected from the group consisting of H, F, and OH;

R 3 is selected from the group consisting of H, F, and OH;

R 4 and R 4a are each independently selected from the group consisting of H, F, and OH;

R 5 is selected from the group consisting of H, F, and OH;

R 6 and R 6a are each H;

R 7 and R 7a are each H;

R 8 and R 8a are each H; and

optionally R 3 and R 6a are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, such that where R 3 and R 6a are connected to form —O—C 1 -C 6 alkylene or —O—C 2 -C 6 alkenylene, said O is bound at the R 3 position.

7. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein

Base 1 and Base 2 are each independently selected from the group consisting of

Y and Y a are each independently selected from the group consisting of —O— and —S—;

X a and X a1 are each O;

X b and X b1 are each O;

X c and X c1 are each independently selected from the group consisting of —SH and —OH;

X d and X d1 are each independently selected from the group consisting of O and S;

R 1 and R 1a are each H;

R 2 is H;

R 2a is selected from the group consisting of H, F, and OH;

R 3 is selected from the group consisting of H, F, and OH;

R 4 is selected from the group consisting of H, F, and OH;

R 4a is H;

R 5 is selected from the group consisting of H, F, and OH;

R 6 and R 6a are each H;

R 7 and R 7a are each H; and

R 8 and R 8a are each H.

8. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition, said pharmaceutical composition comprising:

(a) a compound according to claim 1 or a pharmaceutically acceptable salt thereof; and

(b) a pharmaceutically acceptable carrier.

10. A method of inducing an immune response in a subject, said method comprising administering a therapeutically effective amount of a compound according to claim 1 to the subject.

11. A method of inducing an immune response in a subject, said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to claim 9 to the subject.

12. A method of inducing a STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a compound according to claim 1 to the subject.

13. A method of inducing a STING-dependent type I interferon production in a subject, said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to claim 9 to the subject.

14. A method of treating a cell proliferation disorder in a subject, said method comprising administering a therapeutically effective amount of a compound according to claim 1 to the subject.

15. The method of claim 14 , wherein the cell proliferation disorder is cancer.

16. A method of treating a cell proliferation disorder in a subject, said method comprising administering a therapeutically effective amount of a pharmaceutical composition according to claim 9 to the subject.

17. The method of claim 16 , wherein the cell proliferation disorder is cancer.