Therapeutic compounds and uses thereof

1. A compound of formula (Ia) or (If):

or a salt thereof, wherein:

X is NH;

ring A is substituted with one or more groups R b that are independently selected from the group consisting of R c , —I, —NO 2 , —N(R d ) 2 , —CN, —C(O)—N(R d ) 2 , —S(O)—N(R d ) 2 , —S(O) 2 —N(R d ) 2 , —O—R d , —S—R d , —O—C(O)—R d , —O—C(O)—O—R d , —C(O)—R d , —S(O)—R d , —S(O) 2 —R d , —O—C(O)—N(R d ) 2 , —N(R d )—C(O)—OR d , —N(R d )—C(O)—N(R d ) 2 , —N(R d )—C(O)—R d , —N(R d )—S(O)—R d , —N(R d )—S(O) 2 —R d , —N(R d )—S(O)—N(R d ) 2 , —CH═C(Re) 2 , and —N(R d )—S(O) 2 —N(R d ) 2 ;

each R c is independently selected from the group consisting of C 2-6 alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, wherein any C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl is optionally substituted with one or more groups R f ;

each R f is independently selected from the group consisting of oxo, 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, halo, —NO 2 , —N(R g ) 2 , —CN, —C(O)—N(R g ) 2 , —S(O)—N(R g ) 2 , —S(O) 2 —N(R g ) 2 , —O—R g , —S—R g , —O—C(O)—R g , —C(O)—R g , —C(O)—O—R g , —S(O)—R g , —S(O) 2 —R g , —C(O)—N(R g ) 2 , —N(R g )—C(O)—R g , —Si(R h ) 3 , —N(R g )—C(O)—O—R g , —N(R g )—S(O)—R g , N(R g )—S(O) 2 —R g , and C 1-6 alkyl, which 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1-6 alkyl are optionally substituted with one or more groups R i ,

each R g is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl is optionally substituted with one or more groups R j , or two R g are taken together with the nitrogen to which they are attached to form a 3-20 membered heterocyclyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo and C 1-3 alkyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo and halo;

each R h is independently selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-6 carbocyclyl;

each R j is independently selected from the group consisting of oxo, halo, amino, hydroxyl, —Si(R k ) 3 , 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl, wherein any 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, C 1 -C 4 alkyl, and halo;

each R k is independently selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-6 carbocyclyl;

each R i is independently selected from the group consisting of oxo, halo, C 1-6 alkyl, cyano, —N(R l ) 2 , —S(O)—R l , —S(O) 2 —R l , —S(O)—N(R l ) 2 , —S(O) 2 —N(R l ) 2 , —N(R l )—S(O)—R l , —N(R l )—C(O)—O—R l , —N(R l )—S(O) 2 —R l , 3-20 membered heterocyclyl, and 3-20 membered carbocyclyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, and C 1-6 alkyl;

each R l is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2 -6alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl is optionally substituted with one or more groups R m ; or two R l are taken together with the nitrogen to which they are attached to form a 3-20 membered heterocyclyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo and C 1-3 alkyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo and halo; and

each R m is independently selected from the group consisting of oxo, halo, amino, hydroxyl, —Si(R n ) 3 , 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl, wherein any 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, C 1 -C 4 alkyl, and halo;

each R n is independently selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-6 carbocyclyl;

each R d is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2 -6alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl is optionally substituted with one or more groups R o , or two R d are taken together with the nitrogen to which they are attached to form a 3-20 membered heterocyclyl that is optionally substituted with one or more groups independently selected from the group consisting of oxo, halo and C 1-3 alkyl that is optionally substituted with one or more groups independently selected from oxo and halo;

each R o is independently selected from the group consisting of oxo, halo, amino, hydroxyl, cyano, —O—R p , 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl, wherein any C 1 -C 6 alkyl, 3-20 membered carbocyclyl and 3-20 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, C 1 -C 4 alkyl, —O—R q , and halo;

each R p is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl is optionally substituted with one or more groups R r ,

each R r is independently selected from the group consisting of oxo, halo, amino, hydroxyl, —Si(R s ) 3 , 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl, wherein any 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, C 1 -C 4 alkyl, and halo;

each R s is independently selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-6 carbocyclyl;

each R q is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl is optionally substituted with one or more groups R t ,

each R t is independently selected from the group consisting of oxo, halo, amino, hydroxyl, —Si(R u ) 3 , 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl, wherein any 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, C 1 -C 4 alkyl, and halo;

each R u is independently selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-6 carbocyclyl;

two R e groups taken together with the carbon to which they are attached form a 3-20 membered carbocyclyl; and

R b is:

2. The compound of claim 1 wherein ring A is optionally substituted with one or more groups R b that are independently selected from the group consisting of R c , —I, —C(O)—N(R d ) 2 , —O—R d , and —CH═C(R e ) 2 or a salt thereof.

3. The compound of claim 1 which is a compound of formula (Ia):

wherein ring A is optionally substituted with one or more additional groups R b that are independently selected from the group consisting of R c , —I, —NO 2 , —N(R d ) 2 , —CN, —C(O)—N(R d ) 2 , —S(O)—N(R d ) 2 , —S(O) 2 —N(R d ) 2 , —O—R d , —S—R d , —O—C(O)—R d , —O—C(O)—O—R d , —C(O)—R d , —C(O)—O—R d , —S(O)—R d , —S(O) 2 —R d , —O—C(O)—N(R d ) 2 , —N(R d )—C(O)—OR d , —N(R d )—C(O)—N(R d ) 2 , —N(R d )—C(O)—R d , —N(R d )—S(O)—R d , —N(R d )—S(O) 2 —R d , —N(R d )—S(O)—N(R d ) 2 , —CH═C(R e ) 2 , and —N(R d )—S(O) 2 —N(R d ) 2 ; or a salt thereof.

4. The compound of claim 3 , wherein ring A is optionally substituted with one or more additional groups R b that are independently selected from the group consisting of R c , —I, —C(O)—N(R d ) 2 , —O—R d , and —CH═C(R e ) 2 or a salt thereof.

5. The compound of claim 3 wherein R b is ethenyl, ethynyl,

or a salt thereof.

6. The compound of claim 1 which is a compound of formula (Ib):

wherein:

X is NH;

R c is C 2-6 alkenyl, C 2-6 alkynyl, 6-10 membered aryl, and 5-14 membered heteroaryl, wherein any C 2-6 alkenyl, C 2-6 alkynyl, 6-10 membered aryl, and 5-14 membered heteroaryl is optionally substituted with one or more groups R f independently selected from the group consisting of oxo, 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, halo, —NO 2 , —N(R g ) 2 , —CN, —C(O)—N(R g ) 2 , —S(O)—N(R g ) 2 , —S(O) 2 —N(R g ) 2 , —O—R g , —S—R g , —O—C(O)—W, —C(O)—R g , —C(O)—O—R g , —S(O)—R g , —S(O) 2 —R g , —C(O)—N(R g ) 2 , —N(R g )—C(O)—R g , —Si(R h ) 3 , —N(R g )—C(O)—O—R g , —N(R g )—S(O)—R g , N(R g )—S(O) 2 —R g , and C 1-6 alkyl, which 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1-6 alkyl are optionally substituted with one or more groups R i independently selected from the group consisting of oxo, halo, C 1-6 alkyl, cyano, —N(R l ) 2 , —S(O) 2 —R l , —S(O)—N(R l ) 2 , —S(O) 2 —N(R l ) 2 , —N(R l )—S(O)—R l , —N(R l )—C(O)—O—R l , —N(R l )—S(O) 2 —R l , 3-20 membered heterocyclyl, and 3-20 membered carbocyclyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, and C 1-6 alkyl; and

R h is independently selected from the group consisting of H, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-6 carbocyclyl;

or a salt thereof.

7. The compound of claim 6 wherein R c is:

or a salt thereof.

8. The compound of claim 1 which is a compound of formula (Ic):

wherein:

X is NH;

R d is C 1-6 alkyl, 6-10 membered aryl, or 5-10 membered heteroaryl, wherein each C 1-6 alkyl, 6-10 membered aryl, or 5-10 membered heteroaryl is optionally substituted with one or more groups R o independently selected from the group consisting of oxo, halo, amino, hydroxyl, cyano, —O—R p , 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl, wherein any C 1 -C 6 alkyl, 3-20 membered carbocyclyl and 3-20 membered heterocyclyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, C 1 -C 4 alkyl, —O—R q , and halo;

R p is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl is optionally substituted with one or more halo;

R q is C 1-6 alkyl is optionally substituted with one or more halo;

or a salt thereof.

9. The compound of claim 8 wherein R d is:

or a salt thereof.

10. The compound of claim 1 which is a compound of formula (Id):

wherein:

R c is -(6-10 membered aryl)-Y or 5-14 membered heteroaryl, wherein any 6-10 membered aryl and 5-14 membered heteroaryl is optionally substituted with one or more groups independently selected from the group consisting of oxo, 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, halo, —NO 2 , —N(R g ) 2 , —CN, —C(O)—N(R g ) 2 , —S(O)—N(R g ) 2 , —S(O) 2 —N(R g ) 2 , —O—R g , —S—R g , —O—C(O)—W, —C(O)—R g , —C(O)—O—R g , —S(O)—R g , —S(O) 2 —R g , —C(O)—N(R g ) 2 , —N(R g )—C(O)—R g , —Si(R h ) 3 , —N(R g )—C(O)—O—R g , —N(R g )—S(O)—R g , N(R g )—S(O) 2 —R g , and C 1-6 alkyl, which 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1-6 alkyl are optionally substituted with one or more groups R i ;

Y is (6-10 membered aryl) or (5-14 membered heteroaryl) optionally substituted with one or more groups R i ;

each R i is independently selected from the group consisting of oxo, halo, C 1-6 alkyl, cyano, —N(R l ) 2 , —S(O) 2 —R l , —S(O)—N(R l ) 2 , —S(O) 2 —N(R l ) 2 , —N(R l )—S(O)—R l , —N(R l )—C(O)—O—R l , —N(R l )—S(O) 2 —R l , 3-20 membered heterocyclyl, and 3-20 membered carbocyclyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, and C 1-6 alkyl;

each R l is independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl, wherein each C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, 3-20 membered carbocyclyl, and 3-20 membered heterocyclyl is optionally substituted with one or more groups R m ;

each R m is independently selected from the group consisting of oxo, halo, amino, hydroxyl, —Si(R n ) 3 , 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl, wherein any 3-20 membered carbocyclyl, 3-20 membered heterocyclyl, and C 1 -C 6 alkyl is optionally substituted with one or more groups independently selected from the group consisting of oxo, C 1 -C 4 alkyl, and halo; and

each R n is independently selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, and C 3-6 carbocyclyl;

or a salt thereof.

11. The compound claim 10 wherein R c is:

or a salt thereof.

12. The compound of claim 1 which is a compound of formula (If):

wherein:

X is NH; and

R b1 is

13. The compound of claim 12 wherein R b1 is:

14. The compound of claim 1 wherein R b is:

15. A compound selected from the group consisting of:

or a salt thereof.

16. A composition comprising a compound of formula (I) as described in claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, carrier, or vehicle.

17. A method for treating a CBP and/or EP300-mediated disorder in an animal comprising administering a compound of formula (I), or a pharmaceutically acceptable salt thereof as described in claim 1 , to the animal, wherein the CBP and/or EP300-mediated disorder is cancer and the cancer is lung cancer, breast cancer, pancreatic cancer, colorectal cancer, or melanoma.