Methods to treat lymphoplasmacytic lymphoma

1. A compound of Formula (A):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative, thereof;

wherein:

each instance of R A is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted carbocyclyl, OR A1 , N(R A1 ) 2 , —CN, —C(═O)R A1 , —C(═O)OR A1 , —C(═O)N(R A1 ) 2 , —NO 2 , —NR A1 C(═O)R A1 , —NR A1 C(═O)OR A1 , —NR A1 S(═O) 2 R A1 , —S(═O) 2 R A1 , or —S(═O) 2 N(R A1 ) 2 ;

each instance of R B is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —CN, —C(═O)R A1 , —C(═O)OR A1 , —C(═O)N(R A1 ) 2 , —NO 2 , —NR A1 C(═O)R A1 , —NR A1 C(═O)OR A1 , —NR A1 S(═O) 2 R A1 , —S(═O) 2 R A1 , or —S(═O) 2 N(R A1 ) 2 , provided that at least one instance of R B is optionally substituted heterocyclyl, optionally substituted —(CH 2 )(heterocyclyl), optionally substituted —(CH 2 ) 2 (heterocyclyl), or optionally substituted —(CH 2 ) 3 (heterocyclyl);

each instance of R A1 is independently hydrogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two R A1 groups are joined to form an optionally substituted heterocyclic ring;

Ring B is of the formula:

R Y is hydrogen, halogen, or substituted or unsubstituted C 1-6 alkyl;

R X is R D , optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, or —N(R A1 )(R Xa );

each instance of R Xa is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —C(═O)R A1 , —C(═O)OR A1 , —C(═O)N(R A1 ) 2 , —S(═O)R A1 , —S(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , —S(═O) 2 OR A1 , —S(═O) 2 N(R A1 ) 2 , —N(R A1 ) 2 , or a nitrogen protecting group;

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

l is 1, 2, 3, 4, or 5;

-U-Q- is —NR A (C═O)— or —(C═O)NR A —; and

R D is an electrophilic moiety of any one of Formulae (i-1) to (i-18):

R D1 is hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —CN, —NO 2 , —OR D1a , N(R D1a ) 2 , SR D1a , CH 2 OR D1a , —CH 2 N(R D1a ) 2 , —CH 2 SR D1a , —C(═O)R D1a , —C(═O)OR D1a , —C(═O)SR D1a , —C(═O)N(R D1a ) 2 , C(═S)R D1a , —C(═S)OR D1a , —C(═S)SR D1a , —C(═S)N(R D1a ) 2 , —C(═NR D1a )R D1a , —C(═NR D1a )OR D1a , —C(═NR D1a )SR D1a , or —C(═NR D1a )N(R D1a ) 2 , wherein each occurrence of R D1 a is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R D1a groups are joined to form an optionally substituted heterocyclic ring;

R D2 is hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —CN, —NO 2 , —OR D2a , N(R D2a ) 2 , SR D2a , CH 2 OR D2a , —CH 2 N(R D2a ) 2 , —CH 2 SR D2a , —C(═O)R D2a , C(═O)OR D2a , —C(═O)SR D2a , —C(═O)N(R D2a ) 2 , —C(═S)R D2a , C(═S)OR D2a , —C(═S)SR D2a , —C(═S)N(R D2a ) 2 , —C(═NR D2a )R D2a , —C(═NR D2a )OR D2a , C(═NR D2a )SR D2a , or —C(═NR D2a )N(R D2a ) 2 , wherein each occurrence of R D2a is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R D2a groups are joined to form an optionally substituted heterocyclic ring;

R D3 is hydrogen, halogen, optionally substituted acyl, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —CN, —NO 2 , —OR D3a , —N(R D3a ) 2 , —SR D3a , —CH 2 OR D3a , —CH 2 N(R D3a ) 2 , —CH 2 SR D3a , —C(═O)R D3a , —C(═O)OR D3a , —C(═O)SR D3a , —C(═O)N(R D3a ) 2 , —C(═S)R D3a , —C(═S)OR D3a , —C(═S)SR D3a , —C(═S)N(R D3a ) 2 , —C(═NR D3a )R D3a , C(═NR D3a )OR D3a , —C(═NR D3a )SR D3a , ands —C(=NR D3 a)N(R D3 a) 2 , wherein each occurrence of R D3 a is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, or optionally substituted heteroaryl, or two R D3a groups are joined to form an optionally substituted heterocyclic ring;

optionally R D1 and R D3 , or R D2 and R D3 , or R D1 and R D2 are joined to form an optionally substituted carbocyclic or optionally substituted heterocyclic ring;

R D4 is a leaving group;

R D5 is hydrogen, C 1-6 alkyl, or a nitrogen protecting group;

Y Z is —O—, —S—, or —NR D6 —, wherein R D6 is hydrogen, C 1-6 alkyl, or a nitrogen protecting group;

a is 1 or 2; and

z is 0, 1, 2, 3, 4, 5, or 6;

wherein, unless otherwise provided:

each instance of the alkyl is independently C 1-6 alkyl;

each instance of the alkenyl is independently C 2-6 alkenyl;

each instance of the alkynyl is independently C 2-6 alkynyl;

each instance of the carbocyclyl and carbocyclic ring is independently 3- to 10-membered, monocyclic or bicyclic carbocyclyl;

each instance of the heterocyclyl and heterocyclic ring is independently 5- to 10-membered, monocyclic or bicyclic heterocyclyl;

each instance of the aryl is independently 6- or 10-membered, monocyclic or bicyclic aryl; and

each instance of the heteroaryl is independently 5- to 10-membered, monocyclic or bicyclic heteroaryl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein -U-Q- is

3. The compound of claim 1 , wherein the compound is of Formula (A1):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof.

4. The compound of claim 3 , wherein the compound is of Formula (A1-a), (A1-b), (A1-c), or (A1-d):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof,

wherein:

each instance of R Xc is independently hydrogen, halogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, —OR A1 , —N(R A1 ) 2 , —SR A1 , —CN, —C(═O)R A1 , —C(═O)OR A1 , —C(═O)N(R A1 ) 2 , —NO 2 , —N 3 , —NR A1 C(═O)R A1 , —NR A1 C(═O)OR A1 , —NR A1 C(═O)N(R A1 ) 2 , —NR A1 S(═O) 2 R A1 , —NR A1 S(═O)R A1 , —OC(═O)R A1 , —OC(═O)OR A1 , —OC(═O)N(R A1 ) 2 , —S(═O)R A1 , —S(═O)N(R A1 ) 2 , —S(═O) 2 R A1 , or —S(═O) 2 N(R A1 ) 2 .

5. The compound of claim 1 , wherein the compound is of Formula (A3):

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof.

6. The compound of claim 5 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein R D is selected from the group consisting of:

7. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein at least one instance of R A is substituted or unsubstituted, C 1-6 alkyl.

8. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein 1 is 1 or 2.

9. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein at least one instance of R B is substituted or unsubstituted, C 1-6 alkyl.

10. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein at least one instance of R B is substituted or unsubstituted —CH 2 -(piperazinyl).

11. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein at least one instance of R B is C 1-6 haloalkyl.

12. The compound of claim 1 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof.

13. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, and optionally a pharmaceutically acceptable excipient.

14. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein -U-Q-is

15. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein R X is N(R A1 )(R Xa ).

16. The compound of claim 15 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein R A1 is hydrogen.

17. The compound of claim 16 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein R Xa is optionally substituted alkyl or optionally substituted acyl.

18. The compound of claim 16 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein R Xa is optionally substituted heterocyclyl or optionally substituted heteroaryl.

19. The compound of claim 16 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein R Xa is —N(R A1 ) 2 .

20. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein

is of the formula:

21. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, provided that at least one instance of R B is optionally substituted —(CH 2 )(heterocyclyl).

22. The compound of claim 1 , or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, stereoisomer, or isotopically labeled derivative thereof, wherein

is of the formula:

23. The compound of claim 1 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof.