Substituted Fused Bicyclic Compounds and Related Methods of Treatment

1 . A compound of Formula (I-A or a pharmaceutically acceptable salt thereof:

wherein:

ring A is fused to ring B;

ring A is selected from the group consisting of C 3 -C 8 cycloalkyl, 4- to 7-membered heterocyclyl, C 6 -C 10 aryl and 5- to 7-membered heteroaryl, wherein the C 3 -C 8 cycloalkyl, 4- to 7-membered heterocyclyl, C 6 -C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium;

ring B is selected from the group consisting of C 3 -C 8 cycloalkyl, 4- to 7-membered heterocyclyl, C 6 -C 10 aryl and 5- to 7-membered heteroaryl, wherein the C 3 -C 8 cycloalkyl, 4- to 7-membered heterocyclyl, C 6 -C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium;

X is N or CH;

Y is S(═O) 2 , C(═O), or S(═O)(=NR e );

R e is selected from the group consisting of H, C 1 -C 3 alkyl, or C 3 -C 8 cycloalkyl;

E is selected from the group consisting of NR a R b , C 1 -C 3 alkylene-NR a R b , C 1 -C 3 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 8 cycloalkyl, C 1 -C 3 alkylene-(C 3 -C 8 cycloalkyl), 4- to 10-membered heterocyclyl, C 1 -C 3 alkylene-(4- to 10-membered heterocyclyl), C 6 -C 10 aryl, C 1 -C 3 alkylene-(C 6 -C 10 aryl), 5- to 7-membered heteroaryl and C 1 -C 3 alkylene-(5- to 7-membered heteroaryl), wherein the C 1 -C 3 alkylene-NR a R b , C 1 -C 3 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 8 cycloalkyl, C 1 -C 3 alkylene-(C 3 -C 8 cycloalkyl), 4- to 10-membered heterocyclyl, C 1 -C 3 alkylene-(4- to 10-membered heterocyclyl), C 6 -C 10 aryl, C 1 -C 3 alkylene-(C 6 -C 10 aryl), 5- to 7-membered heteroaryl or C 1 -C 3 alkylene-(5- to 7-membered heteroaryl) is unsubstituted or substituted with one or more halogen, hydroxyl, NR c R d , CF 3 , CHF 2 , CH 2 F, C 1 -C 3 alkyl, or C 1 -C 3 alkoxyl;

R a and R b are each, independently, selected from the group consisting of H, C 1 -C 3 alkyl, C 3 -C 8 cycloalkyl, and 4- to 7-membered heterocyclyl, wherein the C 1 -C 3 alkyl, C 3 -C 8 cycloalkyl, or 4- to 7-membered heterocyclyl is unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkyl, or C 1 -C 3 alkoxyl;

or, alternatively, R a and R b , together with the N atom to which they are attached, form a 4- to 7-membered heterocyclyl or 5- to 7-membered heteroaryl, wherein the 4- to 7-membered heterocyclyl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, NR c R d , C 1 -C 3 alkyl, C 1 -C 3 alkoxyl, or C 1 -C 3 alkyl substituted with 1-3 halogen;

R 1 is selected from the group consisting of C(═O)—C 1 -C 4 alkyl, C(═O)—C 1 -C 4 alkoxyl, C(═O)—(CR c R d ) n —C 3 -C 8 cycloalkyl, C(═O)—(CR c R d ) n -(4- to 7-membered heterocyclyl), C(═O)—(CR c R d ) n —(C 6 -C 10 aryl), C(═O)—(CR c R d ) n -(5- to 10-membered heteroaryl), C(═O)—O—(CR c R d ) n —C 3 -C 8 cycloalkyl, C(═O)—O—(CR c R d ) n -(4- to 7-membered heterocyclyl), (CR c R d ) n —(C 6 -C 10 aryl) and (CR c R d ) n -(5- to 10-membered heteroaryl), wherein the C 1 -C 4 alkyl, C 1 -C 4 alkoxyl, C 3 -C 8 cycloalkyl, 4- to 7-membered heterocyclyl, C 6 -C 10 aryl, or 5- to 10-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium;

R c and R d are each, independently, H, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium;

n is 0, 1, or 2;

each of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 is, independently, H, halogen, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium;

or, alternatively, R 3 and R 6 , together form an unsubstituted C 1 -C 3 alkylene or a C 1 -C 3 alkylene substituted with one or more halogen;

or, alternatively, R 4 and R 5 , together form an unsubstituted C 1 -C 3 alkylene or a C 1 -C 3 alkylene substituted with one or more halogen;

m is 0 or 1;

p is 0, 1, 2, 3, or 4; and

each R 9 is, independently, selected from the group consisting of deuterium, halogen, hydroxyl, and cyano.

2 . The compound according to claim 1 , wherein the compound of Formula (I-A) or a pharmaceutically acceptable salt thereof is a compound of Formula (I) or a pharmaceutically acceptable salt thereof:

3 . The compound according to claim 1 , wherein ring A is selected from the group consisting of: C 3 -C 8 cycloalkyl, 4- to 7-membered heterocyclyl, and 5- to 7-membered heteroaryl, wherein the C 3 -C 8 cycloalkyl, 4- to 7-membered heterocyclyl, or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

4 .- 13 . (canceled)

14 . The compound according to claim 1 , wherein ring B is selected from the group consisting of: 4- to 7-membered heterocyclyl, C 6 -C 10 aryl and 5- to 7-membered heteroaryl, wherein the 4- to 7-membered heterocyclyl, C 6 -C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

15 .- 26 . (canceled)

27 . The compound according to claim 1 , wherein ring A and ring B are each, independently, selected from the group consisting of: 4- to 7-membered heterocyclyl, C 6 -C 10 aryl and 5- to 7-membered heteroaryl, wherein the 4- to 7-membered heterocyclyl, C 6 -C 10 aryl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

28 .- 35 . (canceled)

36 . The compound according to claim 1 , wherein ring A is 5- to 7-membered heteroaryl and ring B is C 6 -C 10 aryl, wherein the 5- to 7-membered heteroaryl and C 6 -C 10 aryl are each, independently, unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

37 . The compound according to claim 1 , wherein ring A is 5- to 7-membered heteroaryl and ring B is 5- to 7-membered heteroaryl, wherein each 5- to 7-membered heteroaryl, independently, is unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

38 . The compound according to claim 1 , wherein ring A is 4- to 7-membered heterocyclyl and ring B is C 6 -C 10 aryl, wherein the 4- to 7-membered heterocyclyl and C 6 -C 10 aryl are each, independently, unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

39 . The compound according to claim 1 , wherein ring A is 4- to 7-membered heterocyclyl and ring B is 5- to 7-membered heteroaryl, wherein the 4- to 7-membered heterocyclyl and 5- to 7-membered heteroaryl are each, independently, unsubstituted or substituted with one or more halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

40 .- 41 . (canceled)

42 . The compound according to claim 1 , wherein

is selected from the group consisting of benzoimidazolyl, 1H-pyrazolo[3,4-c]pyridinyl, imidazo[1,5-a]pyridinyl, indolyl, isoindolyl, indolinyl, indazolyl, isoindazolyl, benzothiazolyl, purinyl, benzofuranyl, benzoisoxazolyl, benzoisothiazolyl, isobenzofuranyl, benzothiofuranyl, indoleninyl, pyrano[3,4-b]-pyrrolyl, indoxazinyl, benzoxazolyl, anthranilyl, and indolizinyl, wherein the benzoimidazolyl, 1H-pyrazolo[3,4-c]pyridinyl, imidazo[1,5-a]pyridinyl, indolyl, isoindolyl, indolinyl, indazolyl, isoindazolyl, benzothiazolyl, purinyl, benzofuranyl, benzoisoxazolyl, benzoisothiazolyl, isobenzofuranyl, benzothiofuranyl, indoleninyl, pyrano[3,4-b]-pyrrolyl, indoxazinyl, benzoxazolyl, anthranilyl, and indolizinyl is unsubstituted or substituted with 1-3 substituents selected from halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with 1-3 halogen or deuterium atoms.

43 . The compound according to claim 1 , wherein

is benzoimidazolyl, wherein the benzoimidazolyl is unsubstituted or substituted with 1-3 substituents selected from halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with 1-3 halogen or deuterium atoms.

44 . (canceled)

45 . The compound according to claim 1 , wherein

is imidazo[1,5-a]pyridinyl, wherein the imidazo[1,5-a]pyridinyl is unsubstituted or substituted with 1-3 substituents selected from halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with 1-3 halogen or deuterium atoms.

46 . The compound according to claim 1 , wherein

is indolyl, wherein the indolyl is unsubstituted or substituted with 1-3 substituents selected from halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with 1-3 halogen or deuterium atoms.

47 - 48 . (canceled)

49 . The compound according to claim 1 , wherein

is indazolyl, wherein the indazolyl is unsubstituted or substituted with 1-3 substituents selected from halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with 1-3 halogen or deuterium atoms.

50 .- 60 . (canceled)

61 . The compound according to claim 1 , wherein

is benzoxazolyl, wherein the benzoxazolyl is unsubstituted or substituted with 1-3 substituents selected from halogen, hydroxyl, C 1 -C 3 alkoxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with 1-3 halogen or deuterium atoms.

62 .- 68 . (canceled)

69 . The compound according to claim 1 , wherein p is 0, 1, or 2.

70 . (canceled)

71 . The compound according to claim 1 , wherein E is NR a R b .

72 . The compound according to claim 1 , wherein E is C 1 -C 3 alkylene-NR a R b .

73 .- 92 . (canceled)

93 . The compound according to claim 1 , wherein E is C 1 -C 3 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 8 cycloalkyl, C 1 -C 3 alkylene-(C 3 -C 8 cycloalkyl), 4- to 10-membered heterocyclyl, or C 1 -C 3 alkylene-(4- to 10-membered heterocyclyl), wherein the C 1 -C 3 alkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 3 -C 8 cycloalkyl, C 1 -C 3 alkylene-(C 3 -C 8 cycloalkyl), 4- to 10-membered heterocyclyl, or C 1 -C 3 alkylene-(4- to 10-membered heterocyclyl) is unsubstituted or substituted with one or more halogen, hydroxyl, NR c R d , CF 3 , CHF 2 , CH 2 F, C 1 -C 3 alkyl, or C 1 -C 3 alkoxyl.

94 .- 108 . (canceled)

109 . The compound according to claim 1 , wherein Y is S(═O) 2 .

110 . The compound according to claim 1 , wherein Y is C(═O).

111 .- 112 . (canceled)

113 . The compound according to claim 1 , wherein X is CH.

114 . The compound according to claim 1 , wherein R 1 is selected from the group consisting of C(═O)—C 1 -C 4 alkyl, C(═O)—C 1 -C 4 alkoxyl, C(═O)—(CR c R d ) n —C 3 -C 8 cycloalkyl, C(═O)—(CR c R d ) n -(4- to 7-membered heterocyclyl), C(═O)—(CR c R d ) n —(C 6 -C 10 aryl), and C(═O)—(CR c R d ) n -(5- to 10-membered heteroaryl), wherein the C 1 -C 4 alkyl, C 1 -C 4 alkoxyl, C 3 -C 8 cycloalkyl, 4- to 7-membered heterocyclyl, C 6 -C 10 aryl, or 5- to 10-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

115 . The compound according to claim 1 , wherein R 1 is selected from the group consisting of C(═O)—C 1 -C 4 alkyl, C(═O)—C 1 -C 4 alkoxyl, and C(═O)—(CR c R d ) n —C 3 -C 8 cycloalkyl, wherein the C 1 -C 4 alkyl, C 1 -C 4 alkoxyl, or C 3 -C 8 cycloalkyl, is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

116 . The compound according to claim 1 , wherein R 1 is selected from the group consisting of C(═O)—(CR c R d ) n -(4- to 7-membered heterocyclyl), C(═O)—(CR c R d ) n —(C 6 -C 10 aryl), and C(═O)—(CR c R d ) n -(5- to 10-membered heteroaryl), wherein the 4- to 7-membered heterocyclyl, C 6 -C 10 aryl, or 5- to 10-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

117 .- 133 . (canceled)

134 . The compound according to claim 1 , wherein R 1 is C(═O)—O—(CR c R d ) n —C 3 -C 8 cycloalkyl or C(═O)—O—(CR c R d ) n -(4- to 7-membered heterocyclyl), wherein the C 3 -C 8 cycloalkyl or 4- to 7-membered heterocyclyl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

135 .- 141 . (canceled)

142 . The compound according to claim 1 , wherein R 1 is (CR c R d ) n —(C 6 -C 10 aryl) or (CR c R d ) n -(5- to 10-membered heteroaryl) wherein the C 6 -C 10 aryl or 5- to 10-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

143 .- 159 . (canceled)

160 . The compound according to claim 1 , wherein R 1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(5- to 7-membered heteroaryl) wherein the phenyl or 5- to 7-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

161 .- 165 . (canceled)

166 . The compound according to claim 1 , wherein R 1 is (CR c R d ) n -(phenyl) or (CR c R d ) n -(6-membered heteroaryl) wherein the phenyl or 6-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

167 .- 177 . (canceled)

178 . The compound according to claim 1 , wherein R 1 is (CR c R d ) n -(5-membered heteroaryl) wherein the 5-membered heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C 1 -C 3 alkyl, or C 1 -C 3 alkyl substituted with one or more halogen or deuterium.

179 .- 244 . (canceled)

245 . A compound or a pharmaceutically acceptable salt thereof selected from the group consisting of:

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

247 . A method of treating narcolepsy in a subject in need thereof comprising administering to the subject a compound of claim 1 or a pharmaceutically acceptable salt thereof, or a composition thereof.

248 . A method of treating cataplexy in a subject in need thereof comprising administering to the subject a compound of claim 1 or a pharmaceutically acceptable salt thereof, or a composition thereof.

249 - 252 . (canceled)

253 . A pharmaceutical composition comprising a compound of claim 245 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

254 . A method of treating narcolepsy in a subject in need thereof comprising administering to the subject a compound of claim 245 or a pharmaceutically acceptable salt thereof, or a composition thereof.

255 . A method of treating cataplexy in a subject in need thereof comprising administering to the subject a compound of claim 245 or a pharmaceutically acceptable salt thereof, or a composition thereof.

256 . A pharmaceutical composition comprising a compound of claim 2 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

257 . A method of treating narcolepsy in a subject in need thereof comprising administering to the subject a compound of claim 2 or a pharmaceutically acceptable salt thereof, or a composition thereof.

258 . A method of treating cataplexy in a subject in need thereof comprising administering to the subject a compound of claim 2 or a pharmaceutically acceptable salt thereof, or a composition thereof.