COMPOUNDS AND COMPOSITIONS FOR TREATING CONDITIONS ASSOCIATED WITH STING ACTIVITY

1 . A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

R 4 and R 5 are defined according to (AA) or (BB):

R 4 is selected from the group consisting of:

C 1-15 alkyl optionally substituted with 1-6 R a ; and

(Y A 1) n —Y A2 wherein:

n is 0 or 1;

Y A1 is C 1-3 alkylene optionally substituted with 1-3 R a ; and

Y A2 is selected from the group consisting of:

C 3-10 cycloalkyl or C 3-10 cycloalkenyl, each of which is optionally substituted with 1-6 R Y ;

heterocyclyl or heterocycloalkenyl of 3-10 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 1-6 R Y ;

heteroaryl of 5-10 ring atoms, wherein 1-4 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 1-6 R Y ; and

C 6-10 aryl optionally substituted with 1-6 R Y ,

each occurrence of R Y is independently selected from the group consisting of: oxo, R c , R b , and -(L b ) b -R b ,

provided that when Y A2 is phenyl or monocyclic heteroaryl, each of which is optionally substituted with 1-6 R Y , then each occurrence of R Y is independently selected from the group consisting of: —R c , R b , and -(L b ) b -R b ;

R 5 is H or R d ; or

R 4 and R 5 taken together with the nitrogen atom to which each is attached forms a saturated, partially unsaturated, or aromatic ring of 4-12 ring atoms, wherein 0-2 ring atoms (in addition to the nitrogen atom attached to R 4 and R 5 ) is a ring heteroatom each independently selected from the group consisting of: N, N(H), N(R d ), O, and S(O) 0-2 , wherein the ring is optionally substituted with 1-4 substituents each independently selected from the group consisting of oxo, R c , R b , and -(L b ) b -R b ;

m is 0, 1, 2, or 3;

each R 6 is independently selected from the group consisting of R c , R b , and -(L b ) b -R b ;

R 3 is selected from the group consisting of: H and R d ;

Y 1 is selected from the group consisting of: CRI and N;

Y 2 is selected from the group consisting of: CR 1b and N;

Y 3 is selected from the group consisting of: CR 1C and N;

X 1 is selected from the group consisting of: CR 1d , N, N(R 2 ), O, and S;

X 2 is selected from the group consisting of: CR 1e , N, N(R 2 ), O, and S;

X 3 is selected from the group consisting of: CR 1f , N, N(R 2 ), O, and S,

provided that 1-3 of X 1 , X 2 , and X 3 is independently selected from the group consisting of: N, N(R 2 ), O, and S;

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

each occurrence of R 1a , R 1b , and R 1c is independently selected from the group consisting of: H, -(L b ) b -R b , R b , and R c ;

each occurrence of R 1d , R 1e , and R 1f is independently selected from the group consisting of: H, -L b -R b , R b , and R c ;

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

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

C 3-10 cycloalkyl or C 3-10 cycloalkenyl, each of which is optionally substituted with 1-4 R c ;

heterocyclyl or heterocycloalkenyl of 3-10 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 c ;

heteroaryl of 5-10 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 ;

each occurrence of L b is independently 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 ;

each occurrence of b is independently 1, 2, or 3;

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 optionally substituted with —OH, NR′R″, C 1-4 alkoxy, or C 1-4 haloalkoxy; 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, halo, C 1-4 alkoxy, and C 1-4 haloalkoxy; —C(O)R′″; —C(O)OR′″; —CONR′R″; —C(═O)C(═O)R′″; —S(O) 1-2 NR′R″; —S(O) 1-2 R′″; —OH; and C 1-4 alkoxy;

each occurrence of R′ and R″ is independently selected from the group consisting of: H; —OH; and C 1-4 alkyl which is optionally substituted with 1-3 substituents each independently selected from the group consisting of: halo, cyano, C 1-4 alkoxy, C 1-4 haloalkoxy, and —OH; and

R′″ is selected from the group consisting of H; and C 1-4 alkyl which is optionally substituted with 1-3 substituents each independently selected from the group consisting of: halo, cyano, C 1-4 alkoxy, C 1-4 haloalkoxy, and —OH;

provided that:

(iii) when the compound is a compound having formula

 then R 1f is other than

 wherein R d2 is H or R d ; and

(iv) the compound is other than:

2 . The compound of claim 1 , wherein the compound is a compound of Formula (I-a):

or a pharmaceutically acceptable salt thereof; or

wherein the compound is a compound of Formula (I-a1):

or a pharmaceutically acceptable salt thereof, and

optionally wherein m is 1 or 2 in Formula (I-a) or (I-a1), or optionally wherein m is 1.

3 . The compound of claims 1 or 2 , wherein wherein the compound is a compound of Formula (I-a1-a):

or a pharmaceutically acceptable salt thereof, wherein:

m1 is 0 or 1.

4 . The compound of any one of claims 1 - 3 , wherein R 4 and R 5 are defined according to (AA).

5 . The compound of any one of claims 1 - 4 , wherein R 4 is —(Y A1 ) n —Y A2 optionally wherein n is 0, and

Y A2 is selected from the group consisting of:

heteroaryl of 5-10 ring atoms, wherein 1-4 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 1-6 R Y ; and

C 6-10 aryl optionally substituted with 1-6 R; or

wherein Y A2 is selected from the group consisting of:

monocyclic 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 1-3 R; and

phenyl optionally substituted with 1-4 R; or

wherein Y A2 is selected from the group consisting of:

bicyclic heteroaryl of 8-10 ring atoms, wherein 1-4 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 1-6 R; and

bicyclic C 8-10 aryl optionally substituted with 1-6 R Y .

6 . The compound of any one of claims 1 - 5 , wherein each R Y 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 1-4 alkoxy optionally substituted with —OH, NR′R″, C 1-4 alkoxy or C 1-4 haloalkoxy; C 1-4 haloalkoxy; —S(O) 1-2 (C 1-4 alkyl); —NR e R f ; —OH; —S(O) 1-2 NR′R″; —C 1-4 thioalkoxy; —C(═O)(C 1-10 alkyl); —C(═O)O(C 1-4 alkyl); —C(═O)OH; and —C(═O)NR′R″, or

wherein each R Y is independently selected from the group consisting of: halo; cyano; C 1-6 alkyl; C 1-6 alkyl substituted with 1-6 independently selected halo; C 1-4 alkoxy; C 1-4 haloalkoxy; and —C(═O)NR′R″, such as —C(═O)NHCH 3 .

7 . The compound of any one of claims 1 - 6 , wherein R 5 is H.

8 . The compound of any one of claims 1 - 3 , wherein R 4 and R 5 are defined according to (BB).

9 . The compound of any one of claims 1 - 8 , wherein each occurrence of R 6 is an independently selected R c ;

optionally wherein each occurrence of R 6 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 1-4 alkoxy optionally substituted with —OH, NR′R″, C 1-4 alkoxy, or C 1-4 haloalkoxy; C 1-4 haloalkoxy; —S(O) 1-2 (C 1-4 alkyl); —NR e R f ; —OH; —S(O) 1-2 NR′R″; —C 1-4 thioalkoxy; —C(═O)(C 1-10 alkyl); —C(═O)O(C 1-4 alkyl); —C(═O)OH; and —C(═O)NR′R″; and

optionally wherein one occurrence of R 6 is cyano.

10 . The compound of any one of claims 1 - 9 , wherein Y 1 is CR 1a ; optionally Y 2 is CR 1b ; and optionally Y 3 is CR 1c .

11 . The compound of any one of claims 1 - 10 , wherein Y 1 is CH; Y 2 is CH; and Y 3 is CH; or

wherein wherein Y 1 is CR 1a , wherein R 1a is selected from the group consisting of: -(L b ) b -R b , R b , and R c ; Y 2 is CH; and Y 3 is CH.

12 . The compound of any one of claims 1 - 11 , wherein X 1 is N(R 2 ); and X 2 is CR 1e , or wherein X 1 is N(H); and X 2 is CH.

13 . The compound of any one of claims 1 - 9 , wherein wherein the

optionally wherein R 2 is H.

14 . The compound of claim 1 , wherein the compound is a compound of Formula (I-a1-a1):

or a pharmaceutically acceptable salt thereof, wherein:

m1 is 0 or 1; and

R 4 is —Y A2 , wherein Y A2 is selected from the group consisting of:

monocyclic 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 1-3 R Y ; and

phenyl optionally substituted with 1-4 R Y ;

optionally wherein R 2 is H.

15 . The compound of claim 1 , wherein the compound is a compound of Formula (I-a1-a2):

or a pharmaceutically acceptable salt thereof, wherein:

m1 is 0 or 1; and

R 4 is —Y A2 , wherein Y A2 is selected from the group consisting of:

bicyclic heteroaryl of 9-10 ring atoms, wherein 1-4 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 1-6 R Y ; and

bicyclic C 9-10 aryl optionally substituted with 1-6 R Y ; and

optionally wherein R 2 is H.

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 claims 1 - 16 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 any one of claims 1 - 16 , or a pharmaceutically acceptable salt thereof; or a pharmaceutical composition as claimed in claim 17 .

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 any one of claims 1 - 16 , or a pharmaceutically acceptable salt thereof; or a pharmaceutical composition as claimed in claim 17 .

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, comprising administering to a subject in need of such treatment an effective amount of a compound as claimed in any one of claims 1 - 16 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition as claimed in claim 17 .