DEUTERATED HETEROARYL SULFONAMIDES AND THEIR USE

1 . A compound of the formula (I):

wherein

Ar is selected from the group consisting of substituted or unsubstituted optionally deuterated C 6-10 aryl and substituted or unsubstituted optionally deuterated 5- to 10-membered heteroaryl;

R 1 is selected from the group consisting of hydrogen or deuterium, substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated C 2-6 alkenyl, substituted or unsubstituted optionally deuterated C 2-6 alkynyl, and substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl;

Y 1 is selected from the group consisting of —CR 2a —, —N—, and —N + (O) − —;

Y 2 is selected from the group consisting of —CR 2b —, —N—, and —N + (O) − —;

Y 3 is selected from the group consisting of —CR 2c —, —N—, and —N + (O) − —;

R 2a , R 2b , and R 2c are each independently selected from the group consisting of hydrogen or deuterium, halogen, —CN, —C(O)R 3 , —CO 2 R 3 , —C(O)NR 3 R 4 , —OR 3 , —OC(O)R 3 , —OC(O)NR 3 R 4 , —SR 3 , —S(O)R 3 , —S(O) 2 R 3 , —S(O) 2 NR 3 R 4 , —NO 2 , —NR 3 R 4 , —NR 3 C(O)R 4 , —NR 3 C(O)OR 4 , —NR 3 S(O) 2 R 4 , —NR 3 C(O)NR 4 R 5 , substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated C 2-8 alkenyl, substituted or unsubstituted optionally deuterated C 2-8 alkynyl, substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl, substituted or unsubstituted optionally deuterated C 6-10 aryl, and substituted or unsubstituted optionally deuterated 5- to 10-membered heteroaryl;

R 3 , R 4 , and R 5 are each independently selected from the group consisting of hydrogen or deuterium, substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated C 2-8 alkenyl, substituted or unsubstituted optionally deuterated C 2-8 alkynyl, substituted or unsubstituted optionally deuterated C 6-10 aryl, substituted or unsubstituted optionally deuterated 5- to 10-membered heteroaryl, and substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl;

R 3 and R 4 , R 4 and R 5 or R 3 and R 5 may, together with the atoms to which they are attached, form a substituted or unsubstituted optionally deuterated 5-, 6-, or 7-membered ring;

L is selected from the group consisting of a bond, —O—, —S—, —S(O)—, —S(O) 2 —,

—CR 6 R 7 —, —NR 8 —, —C(O)— and —NR 8 C(O)—;

R 6 and R 7 are each independently selected from the group consisting of hydrogen or deuterium, halogen, substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl, substituted or unsubstituted optionally deuterated C 2-6 alkenyl, substituted or unsubstituted optionally deuterated C 2-6 alkynyl, —CN, —OR 9 , —NR 10 R 11 , —S(O)R 9 , and —S(O) 2 R 9 ;

R 6 and R 7 may, together with the carbon atom to which they are attached, form substituted or unsubstituted optionally deuterated C 3-8 cycloalkyl or substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclic ring;

R 9 is selected from the group consisting of hydrogen or deuterium, substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated C 2-8 alkenyl, substituted or unsubstituted optionally deuterated C 2-8 alkynyl, substituted or unsubstituted optionally deuterated C 6-10 aryl, substituted or unsubstituted optionally deuterated 5- to 10-membered heteroaryl, and substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl;

R 10 and R 11 are each independently selected from the group consisting of substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl, substituted or unsubstituted optionally deuterated C 6-10 aryl, substituted or unsubstituted optionally deuterated 5- to 10-membered heteroaryl, substituted or unsubstituted optionally deuterated C 2-8 alkenyl, and substituted or unsubstituted optionally deuterated C 2-8 alkynyl;

R 10 and R 11 of —NR 10 R 11 may, together with the nitrogen, form a substituted or unsubstituted optionally deuterated C 3-8 cycloalkyl or substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl;

R 8 is selected from the group consisting of hydrogen or deuterium,

—C(O)R 12 , —S(O) 2 R 12 , —CO 2 R 12 , substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl, substituted or unsubstituted optionally deuterated C 2-6 alkenyl, and substituted or unsubstituted optionally deuterated C 2-6 alkynyl;

R 12 is selected from the group consisting of substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated C 2-6 alkenyl, substituted or unsubstituted optionally deuterated C 2-6 alkynyl, substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl, substituted or unsubstituted optionally deuterated C 6-10 aryl, and substituted or unsubstituted optionally deuterated 5- to 10-membered heteroaryl;

Z 1 is selected from the group consisting of substituted or unsubstituted optionally deuterated C 6-10 aryl, substituted or unsubstituted optionally deuterated 5- to 10-membered heteroaryl, substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl, and —NR 13 R 14 ;

R 13 and R 14 are each independently selected from the group consisting of hydrogen or deuterium, substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated C 2-8 alkenyl, substituted or unsubstituted optionally deuterated C 2-8 alkynyl, substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl, substituted or unsubstituted optionally deuterated C 6-10 aryl, substituted or unsubstituted optionally deuterated 5- to 10-membered heteroaryl, substituted or unsubstituted optionally deuterated (C 1-4 alkyl)-(C 6-10 aryl), and substituted or unsubstituted optionally deuterated (C 1-4 alkyl)-(5- to 10-membered heteroaryl);

R 13 and R 14 may, together with the nitrogen, form a substituted or unsubstituted optionally deuterated 4-, 5-, 6-, or 7-membered heterocyclyl;

Y 4 is selected from the group consisting of —N— and —N + (O) − —; and wherein the compound comprises at least one deuterium above natural isotopic abundance;

or a pharmaceutically acceptable salt thereof.

2 . The compound of claim 1 , wherein at least one of Y 1 , Y 2 , Y 3 , or Z 1 comprises deuterium above natural isotopic abundance,

3 . A compound of the formula (II):

wherein

each of Q 1 and Q 2 independently is hydrogen, deuterium, halogen, optionally deuterated C 1-8 alkyl, —CN, or optionally deuterated C 1-8 haloalkyl;

each Q 3a , Q 3b , Q 3c independently is hydrogen or deuterium;

Q 4 is hydrogen or deuterium;

Q 5 is halogen or optionally deuterated C 1-8 alkyl;

Q 6 is hydrogen or deuterium;

each of X 1 , X 2 , X 4 , X 6 , and X 7 independently is —CQ 7 —, —N—, or —NO—;

X 3 is —CQ 7 —;

each Q 7 independently is hydrogen or deuterium, halogen, substituted or unsubstituted optionally deuterated C 1-8 alkyl, substituted or unsubstituted optionally deuterated C 2-8 alkenyl, substituted or unsubstituted optionally deuterated C 2-8 alkynyl, —CN, ═O, —NO 2 , —OQ 8 , —OC(O)Q 8 , —CO 2 Q 8 , —C(O)Q 8 , —C(O)NQ 9 Q 8 , —OC(O)NQ 9 Q 8 , —NQ 10 C(O)Q 8 , —NQ 10 C(O)NQ 9 Q 8 , —NQ 9 Q 8 , —NQ 10 CO 2 Q 8 , —SQ 8 , —S(O)Q 8 , —S(O) 2 Q 8 , —S(O) 2 NQ 9 Q 8 , —NQ 10 S(O) 2 Q 8 , substituted or unsubstituted optionally deuterated C 6-10 aryl, substituted or unsubstituted optionally deuterated 5- to 10-membered heteroaryl and substituted or unsubstituted optionally deuterated 3- to 10-membered heterocyclyl;

each occurrence of Q 8 , Q 9 , and Q 10 is independently selected from the group consisting of hydrogen or deuterium, optionally deuterated C 1-8 alkyl, optionally deuterated C 2-8 alkenyl, optionally deuterated C 2-8 alkynyl, optionally deuterated aryl, or optionally deuterated heteroaryl; or Q 9 and Q 8 or Q 10 and Q 8 , together with the atom(s) to which they are attached, form an substituted or unsubstituted optionally deuterated 5-, 6-, or 7-membered ring;

Q 11 is selected from the group consisting of hydrogen, optionally deuterated C 1-8 alkyl, optionally deuterated C 2-8 alkenyl, optionally deuterated C 2-8 alkynyl, optionally deuterated substituted or unsubstituted C 6-10 aryl, optionally deuterated substituted or unsubstituted 5-to 10-membered heteroaryl, and optionally deuterated substituted or unsubstituted 3- to 10-membered heterocycle; and

wherein the compound comprises at least one deuterium above natural isotopic abundance,

or a pharmaceutically acceptable salt thereof.

4 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein at least one of Q 1 or Q 2 is other than hydrogen.

5 . The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein each Q 3a , Q 3b , and Q 3c independently is hydrogen or deuterium.

6 . The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein one or more of Q 4 , Q 5 , Q 6 , or Q 7 comprises deuterium above natural isotopic abundance.

7 . The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein Q 1 is halogen.

8 - 19 . (canceled)

20 . A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof wherein

each Q 4 is independently hydrogen or deuterium;

each Q 6 is independently hydrogen or deuterium;

each Q 7a , Q 7b , Q 7c , Q 7d , Q 7e , Q 7f , Q 7g , Q 7h , Q 7i , Q 7j , Q 7k , Q 7l , Q 7m , Q 7n , Q 7o , independently is hydrogen or deuterium; and

wherein the compound comprises at least one deuterium above natural isotopic abundance.

21 . The compound of claim 20 , wherein, for each compound, one or more of Q 4 , Q 6 , or Q 7 comprises deuterium above natural isotopic abundance.

22 - 27 . (canceled)

28 . A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

29 - 30 . (canceled)