Therapeutic compounds and methods

1. A compound of formula (I):

or a prodrug thereof, or a pharmaceutically acceptable salt thereof, wherein:

R 1 is —NR a R b or a 5-10 membered heteroaryl that is optionally substituted with one or more groups R c ;

R 2 is a 6-10 membered aryl that is optionally substituted with one or more groups R r ; or R 2 is a 5-10 membered heteroaryl that is that is optionally substituted with one or more groups R s ; or R 2 is a 3-10 membered heterocycle that is that is optionally substituted with one or more groups R z ;

R a is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkanoyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkynylcarbonyl, 3-6 membered heterocycle, or a 5-6 membered heteroaryl that is optionally substituted with one or more groups R f ; wherein each (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkanoyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, (C 2 -C 6 )alkynylcarbonyl, and 3-6 membered heterocycle is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, cyano, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, C(═O)NR m R n , and (C 1 -C 6 )alkyl that is optionally substituted with one or more groups independently selected form the group consisting of halo, hydroxy, cyano, —NR m R n , and —C(═O)NR m R n ;

R b is H or (C 1 -C 6 )alkyl;

each R c is independently selected from the group consisting of cyano, —NR d R e , —C(═O)NR d R e , (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, and (C 1 -C 6 )alkanoyl, wherein each (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkyl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy and (C 1 -C 6 )alkanoyl is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, carboxy, and cyano;

R d and R e are each independently selected from the group consisting of H and (C 1 -C 6 )alkyl; or R d and R e are taken together with the nitrogen to which they are attached form a 3-6 membered heterocyclic ring that is optionally substituted with one or more groups independently selected from the group consisting of halo and (C 1 -C 6 )alkyl;

each R f is independently selected from the group consisting of halo, hydroxy, cyano, —NR g R h , —C(═O)NR g R h , and (C 1 -C 6 )alkyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, carboxy, —NR g R h , —C(═O)NR g R h , and cyano;

R g and R h are each independently selected from the group consisting of H and (C 1 -C 6 )alkyl; or R g and R h taken together with the nitrogen to which they are attached form a 3-6 membered heterocyclic ring that is optionally substituted with one or more groups independently selected from the group consisting of halo and (C 1 -C 6 )alkyl;

R m is H or (C 1 -C 6 )alkyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, carboxy, cyano, and oxo;

R n is H or (C 1 -C 6 )alkyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, carboxy, cyano, and oxo;

each R r is independently selected from the group consisting of halo, hydroxy, cyano, —NR t R u , —C(═O)NR t R u , —S(O) 2 NR t R u , (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylthio, —N(H)S(O) 2 R x , —S(O) 2 R x , (C 2 -C 6 )alkenyl, and (C 2 -C 6 )alkynyl, wherein each (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylthio, (C 2 -C 6 )alkenyl, and (C 2 -C 6 )alkynyl is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, carboxy, —NR t R u , —C(═O)NR t R u , —S(O) 2 NR t R u , —S(O) 2 R x , and cyano;

each R s is independently selected from the group consisting of halo, cyano, —NR v R w , —C(═O)NR v R w , —S(O) 2 NR v R w , (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkylthio, 3-6 membered heterocycle, and —S(O) 2 R y , wherein each (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, 3-6 membered heterocycle, and (C 1 -C 6 )alkylthio, is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, carboxy, —NR t R u , —C(═O)NR t R u , S(O) 2 NR v R w , —S(O) 2 R y , and cyano;

R t and R u are each independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkanoyl, and (C 2 -C 6 )alkynylcarbonyl; or R t and R u taken together with the nitrogen to which they are attached form a 3-6 membered heterocyclic ring that is optionally substituted with one or more groups independently selected from the group consisting of halo and (C 1 -C 6 )alkyl;

R v and R w are each independently selected from the group consisting of H, (C 1 -C 6 )alkyl, and (C 1 -C 6 )alkanoyl; or R v and R w taken together with the nitrogen to which they are attached form a 3-6 membered heterocyclic ring that is optionally substituted with one or more groups independently selected from the group consisting of halo and (C 1 -C 6 )alkyl;

R x is H or (C 1 -C 6 )alkyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, carboxy, cyano, and oxo;

R y is H or (C 1 -C 6 )alkyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, carboxy, cyano, and oxo; and

each R z is independently selected from the group consisting of oxo, halo, hydroxy, and (C 1 -C 6 )alkyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy, carboxy, —NR t R u , —C(═O)NR t R u , S(O) 2 NR v R w , —S(O) 2 R y , cyano, and oxo;

provided the compound is not:

2. The compound of claim 1 , wherein:

R 1 is —NR a R b or a 5-10 membered heteroaryl that is optionally substituted with one or more groups R c ;

R 2 is a phenyl that is optionally substituted with one or more groups R r ; or R 2 is a 5-9 membered heteroaryl that is that is optionally substituted with one or more groups R s ; or R 2 is a 9-membered heterocycle that is that is optionally substituted with one or more groups R z ;

R a is (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkanoyl, (C 2 -C 6 )alkynylcarbonyl, 3-6 membered heterocycle, or a 5-membered heteroaryl that is optionally substituted with one or more groups R f ; wherein each (C 1 -C 6 )alkyl and (C 3 -C 6 )cycloalkyl is optionally substituted with one or more groups independently selected from the group consisting of halo, cyano, (C 2 -C 6 )alkynyl, C(═O)NR m R n , and (C 1 -C 6 )alkyl that is optionally substituted with one or more hydroxy;

R b is H or (C 1 -C 6 )alkyl;

each R c is independently selected from the group consisting of cyano, —NR d R e , and (C 1 -C 6 )alkyl that is optionally substituted with one or more cyano;

R d and R e are each H;

each R f is independently selected from the group consisting of halo, hydroxy, cyano, —C(═O)NR g R h , and (C 1 -C 6 )alkyl that is optionally substituted with one or more groups independently selected from the group consisting of halo, hydroxy and carboxy;

R g and R h are each H;

R m is H;

R n is H;

each R r is independently selected from the group consisting of halo, hydroxy, cyano, —NR t R u , —C(═O)NR t R u , —S(O) 2 NR t R u , (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkylthio, —N(H)S(O) 2 R x , —S(O) 2 R x , and (C 2 -C 6 )alkynyl, wherein each (C 1 -C 6 )alkyl and (C 2 -C 6 )alkynyl, is optionally substituted with one or more groups independently selected from the group consisting of hydroxy, —NR t R u , —C(═O)NR t R u , and cyano;

each R s is independently selected from the group consisting of halo, cyano, —NR v R w , —C(═O)NR v R w , (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkanoyl, (C 1 -C 6 )alkylthio, 3-6 membered heterocycle, and —S(O) 2 R y , wherein each (C 1 -C 6 )alkyl is optionally substituted with one or more groups independently selected from the group consisting of halo and —NR t R u ;

R t and R u are each independently selected from the group consisting of H, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkanoyl, and (C 2 -C 6 )alkynylcarbonyl; or R t and R u taken together with the nitrogen to which they are attached form a 3-6 membered heterocyclic ring that is optionally substituted with one or more groups independently selected from the group consisting of halo and (C 1 -C 6 )alkyl;

R v and R w are each independently selected from the group consisting of H, (C 1 -C 6 )alkyl, and (C 1 -C 6 )alkanoyl;

R x is (C 1 -C 6 )alkyl;

R y is (C 1 -C 6 )alkyl; and

each R z is independently selected from the group consisting of oxo and (C 1 -C 6 )alkyl;

or a prodrug thereof, or a pharmaceutically acceptable salt thereof.

3. The compound, prodrug, or pharmaceutically acceptable salt of claim 1 , wherein R 1 is —NR a R b .

4. The compound, prodrug, or pharmaceutically acceptable salt of claim 3 , wherein R a is acetyl.

5. The compound, prodrug, or pharmaceutically acceptable salt of claim 3 , wherein R a is selected from the group consisting of:

6. The compound, prodrug, or pharmaceutically acceptable salt of claim 1 , wherein R 1 is a 5-membered heteroaryl that is optionally substituted with one or more groups R c .

7. The compound, prodrug, or pharmaceutically acceptable salt of claim 1 , wherein R 1 is selected from the group consisting of:

8. The compound, prodrug, or pharmaceutically acceptable salt of claim 1 , wherein R 2 is a 5-9 membered heteroaryl that is optionally substituted with one or more groups R s , or phenyl that is optionally substituted with one or more groups R r .

9. The compound, prodrug, or pharmaceutically acceptable salt of claim 1 , wherein R 2 is selected from the group consisting of:

10. The compound, prodrug, or pharmaceutically acceptable salt of claim 1 , wherein R 2 is:

and R r (C 2 -C 6 )alkynyl that is substituted with hydroxy.

11. The compound, prodrug, or pharmaceutically acceptable salt of claim 1 , wherein R 2 is selected from the group consisting of:

12. The compound, prodrug, or pharmaceutically acceptable salt of claim 1 , which is selected from the group consisting of:

and prodrugs and pharmaceutically acceptable salts thereof.

13. The prodrug of claim 1 , which is a compound of formula (I) that comprises a hydroxy group that has been converted to a prodrug group that increases the aqueous solubility of the compound; or a pharmaceutically acceptable salt thereof.

14. The prodrug or pharmaceutically acceptable salt of claim 13 , wherein the hydroxy group has been converted to a prodrug group selected from the group consisting of: a phosphate,

15. The prodrug or pharmaceutically acceptable salt of claim 1 that is selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

16. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

17. A pharmaceutical composition comprising a compound, prodrug, or pharmaceutically acceptable salt as described in claim 1 and a pharmaceutically acceptable excipient.