COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH STING ACTIVITY

1 . A compound of Formula (I):

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

Y 1 , Y 2 , and Y 3 are independently selected from the group consisting of CR 1 , C(═O), N, and NR 2 ;

X 1 is selected from the group consisting of O, S, N, NR 2 , and CR 1 ;

X 2 is selected from the group consisting of O, S, N, NR 4 , and CR 5 ;

each is independently a single bond or a double bond, provided that the five-membered ring comprising X 1 and X 2 is heteroaryl, and that the six-membered ring comprising Y 1 , Y 2 , and Y 3 is aryl or heteroaryl;

each occurrence of R 1 and R 5 is independently selected from the group consisting of: H; R c ; R h ; and -(L 1 ) b1 -R h ;

each occurrence of R 2 and R 4 is independently selected from the group consisting of: H; R d ; R g ; and -(L 2 ) b2 -R g ;

R 6 is selected from the group consisting of: H; R d ; and R h ;

Q 1 is selected from the group consisting of:

C 3-12 cycloalkylene or C 3-12 cycloalkenylene, each optionally substituted with 1-4 substituents independently selected from the group consisting of oxo, R c and R h ;

heterocyclylene or heterocycloalkenylene of 3-12 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heterocyclylene or heterocycloalkenylene is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo, R c , and R h ;

heteroarylene of 5-12 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heteroarylene is optionally substituted with 1-4 substituents independently selected from the group consisting of R c and R h ; and

C 6-10 arylene optionally substituted with 1-4 substituents independently selected from the group consisting of R c and R h ;

each L A is independently selected from the group consisting of: C 1-3 alkylene optionally substituted with 1-2 R a1 ; —O—; —NH—; —NR d ; —S(O) 0-2 ; and C(O);

a1 is 0, 1, 2, 3, or 4;

Q 2 is selected from the group consisting of: H; R g ; and R c ;

W is selected from the group consisting of:

H;

C 1-10 alkyl, C 2-10 alkenyl, or C 2-10 alkynyl, each of which is optionally substituted with 1-6 R a2 ;

monocyclic C 3-8 cycloalkyl or C 3-8 cycloalkenyl, each of which is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo and R c ; and

monocyclic heterocyclyl or heterocycloalkenyl of 3-8 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo and R c , provided that when W is heterocyclyl or heterocycloalkenyl, it is attached to the C(═O)NR 6 group via a ring carbon atom;

each occurrence of R a , R a1 , and R a2 is independently selected from the group consisting of: —OH; -halo; —NR e R f ; C 1-4 alkoxy; C 1-4 haloalkoxy; —C(═O)O(C 1-4 alkyl); —C(═O)(C 1-4 alkyl); —C(═O)OH; —CONR′R″; —S(O) 1-2 NR′R″; —S(O) 1-2 (C 1-4 alkyl); and cyano;

each occurrence of R c is independently selected from the group consisting of: halo; cyano; C 1-10 alkyl which is optionally substituted with 1-6 independently selected R a ; C 2-6 alkenyl; C 2-6 alkynyl; C 1-4 alkoxy; C 1-4 haloalkoxy; —S(O) 1-2 (C 1-4 alkyl); —S(O)(═NH)(C 1-4 alkyl); —NR e R f ; —OH; —S(O) 1-2 NR′R″; —C 1-4 thioalkoxy; —NO 2 ; —C(═O)(C 1-10 alkyl); —C(═O)O(C 1-4 alkyl); —C(═O)OH; —C(═O)NR′R″; and —SF 5 ;

each occurrence of R d is independently selected from the group consisting of: C 1-6 alkyl optionally substituted with 1-3 independently selected R a ; —C(O)(C 1-4 alkyl); —C(O)O(C 1-4 alkyl); —CONR′R″; —S(O) 1-2 NR′R″; —S(O) 1-2 (C 1-4 alkyl); —OH; and C 1-4 alkoxy;

each occurrence of R e and R f is independently selected from the group consisting of: H; C 1-6 alkyl optionally substituted with 1-3 substituents each independently selected from the group consisting of NR′R″, —OH, and R i ; —C(O)(C 1-4 alkyl); —C(O)O(C 1-4 alkyl); —CONR′R″; —S(O) 1-2 NR′R″; —S(O) 1-2 (C 1-4 alkyl); —OH; and C 1-4 alkoxy;

each occurrence of R g is independently selected from the group consisting of:

C 3-12 cycloalkyl or C 3-12 cycloalkenyl, each of which is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo, R c , R h , and -(L g ) bg -R h ;

heterocyclyl or heterocycloalkenyl of 3-12 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo, R c , R h , and -(L g ) bg -R h ;

heteroaryl of 5-12 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heteroaryl is optionally substituted with 1-4 substituents independently selected from the group consisting of R c , R h , and -(L g ) bg -R h ; and

C 6-10 aryl optionally substituted with 1-4 substituents independently selected from the group consisting of R c , R h , and -(L g ) bg -R h ;

each occurrence of R h is independently selected from the group consisting of:

C 3-8 cycloalkyl or C 3-8 cycloalkenyl, each of which is optionally substituted with 1-4 R i ;

heterocyclyl or heterocycloalkenyl of 3-8 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with 1-4 R i ;

heteroaryl of 5-6 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heteroaryl is optionally substituted with 1-4 R i ; and

C 6 aryl optionally substituted with 1-4 R i ;

each occurrence of R i is independently selected from the group consisting of: C 1-6 alkyl; C 1-4 haloalkyl; C 1-4 alkoxy; C 1-4 haloalkoxy; and halo;

each occurrence of L 1 , L 2 , and L g is selected from the group consisting of: —O—, —NH—, —NR d , —S(O) 0-2 , C(O), and C 1-3 alkylene optionally substituted with 1-3 R a ;

b1, b2, and bg are each independently 1, 2, or 3; and

each occurrence of R′ and R″ is independently selected from the group consisting of: H; —OH; and C 1-4 alkyl;

provided that when Y 1 and Y 2 are CH; Y 3 is N; W is unsubstituted n-propyl; and Q 1 is unsubstituted phenylene, then: -(L A ) a1 -Q 2 is other than —CH 2 -morpholinyl, —CH 2 —N-methylpiperazinyl, morpholinyl, or N-methylpiperazinyl.

2 . The compound of claim 1 , wherein Q 3 is heteroarylene of 5-12 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heteroarylene is optionally substituted with 1-4 substituents independently selected from the group consisting of R c and R h ; such as:

wherein Q 1 is heteroarylene of 5-6 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S, and wherein the heteroarylene is optionally substituted with 1-3 R c ; such as:

wherein Q 1 is heteroarylene of 5 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S, and wherein the heteroarylene is optionally substituted with 1-2 R c ; such as:

wherein Q 1 is pyrazolylene which is optionally substituted with 1-2 R c ; such as:

wherein Q 1 is

which is optionally substituted with 1-2 R c (such as unsubstituted), wherein aa represents point of attachment to -(L A ) a1 -Q 2 .

3 . The compound of claim 1 , wherein a1 is 0; or wherein a1 is 1, and L A is C 1-3 alkylene optionally substituted with 1-2 R a1 .

4 . The compound of claim 1 , wherein Q 2 is R g .

5 . The compound of claim 1 , wherein Q 2 is selected from the group consisting of:

heteroaryl of 5-12 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heteroaryl is optionally substituted with 1-4 substituents independently selected from the group consisting of R c , R h , and -(L g ) bg -R h ; and

C 6-10 aryl optionally substituted with 1-4 substituents independently selected from the group consisting of R c , R h , and -(L g ) bg -R h .

6 . The compound of claim 1 , wherein 1, 2, or 3 of Y 1 , Y 2 , and Y 3 is an independently selected CR 1 , and wherein each R 1 is independently H or R c .

7 . The compound of claim 1 , wherein X 1 is NR 2 ; and X 2 is CR 5 , optionally wherein X 1 is NH; and X 2 is CH.

8 . The compound of claim 1 , wherein W is C 1-10 alkyl, C 2-10 alkenyl, or C 2-10 alkenyl, each of which is optionally substituted with 1-6 R a2 ; such as:

wherein W is C 1-10 alkyl, which is optionally substituted with 1-6 R a2 ; such as:

wherein W is C 1-6 , such as C 1 , C 2 , C 3 , or C 4 , alkyl, which is optionally substituted with 1-6 R a2 ; such as:

wherein W is selected from the group consisting of: methyl, ethyl, propyl, isopropyl, and isobutyl, each of which is optionally substituted with 1-3 R a2 .

9 . The compound of claim 1 , wherein W is selected from the group consisting of:

monocyclic C 3-8 cycloalkyl or C 3-8 cycloalkenyl, each of which is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo and R c ; and

monocyclic heterocyclyl or heterocycloalkenyl of 3-8 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heterocyclyl or heterocycloalkenyl is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo and R c .

10 . The compound of claim 1 , wherein W is cyclobutyl, cyclopentyl, or cyclohexyl, each of which is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo and R c ; or

wherein W is azetidinyl, oxetanyl, pyrrolidinyl, or tetrahydrofuranyl, each of which is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo and R c ;

and the ring nitrogen atom when present is optionally substituted with R d .

11 . The compound of claim 1 , wherein the compound is a compound of Formula (Ia):

or a pharmaceutically acceptable salt thereof or a tautomer thereof.

12 . The compound of claim 11 , wherein Y 1 , Y 2 , and Y 3 are each an independently selected CR 1 ; and optionally R 2 is H; and optionally R 5 is H, such as:

wherein Y 1 , Y 2 , and Y 3 are each an independently selected CR 1 ; R 2 is H; and R 5 is H.

13 . The compound of claim 11 , wherein Q 2 is selected from the group consisting of:

heteroaryl of 5-6 ring atoms, wherein 1-3 ring atoms are heteroatoms, each independently selected from the group consisting of N, N(H), N(R d ), O, and S(O) 0-2 , and wherein the heteroaryl is optionally substituted with 1-4 R c ; and

C 6-10 aryl optionally substituted with 1-4 R c .

14 . The compound of claim 11 , wherein W is C 1-6 (such as C 1 , C 2 , C 3 , or C 4 ) alkyl, which is optionally substituted with 1-6 R a2 ; such as:

wherein W is unsubstituted C 1-6 alkyl, such as methyl, ethyl, propyl, isopropyl, or isobutyl, such as methyl or ethyl, such as ethyl.

15 . The compound of claim 11 , wherein W is monocyclic C 3-8 cycloalkyl (e.g., C 3-6 cycloalkyl) optionally substituted with 1-4 substituents independently selected from the group consisting of oxo and R c , such as wherein W is cyclobutyl, cyclopentyl, or cyclohexyl, each of which is optionally substituted with 1-4 substituents independently selected from the group consisting of oxo and R c , such as unsubstituted cyclobutyl, cyclopentyl, or cyclohexyl.

16 . The compound of claim 1 , wherein the compound is selected from the group consisting of the compounds delineated in Table C1 or a pharmaceutically acceptable salt thereof.

17 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

18 . A method for inhibiting STING activity, the method comprising contacting STING with a compound as claimed in claim 1 , or a pharmaceutically acceptable salt thereof.

19 . A method of inducing an immune response in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound as claimed in claim 1 , or a pharmaceutically acceptable salt thereof.

20 . A method of treatment of disease, disorder, or condition associated with STING, such as a disease, disorder, or condition, in which increased STING signaling, such as excessive STING signaling, contributes to the pathology and/or symptoms and/or progression of the disease, such as cancer, comprising administering to a subject in need of such treatment an effective amount of a compound as claimed in claim 1 , or a pharmaceutically acceptable salt thereof.