Substituted Macrocyclic Compounds and Related Methods of Treatment

1 - 67 . (canceled)

68 . A compound of Formula II-A or a pharmaceutically acceptable salt thereof:

wherein:

ring A is selected from the group consisting of phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl;

n is 1, 2, or 3;

T is CR 1 R 2 or 0;

W is CR 4 R 5 or 0;

U is CR 6 R 7 ;

X is CR 8 R 9 ;

V is CR 3 or N;

Y is NR 10 , O or absent;

Z is (CR 12 R 13 ) m ;

R is halogen or deuterium; and

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

and further wherein:

m is 2, 3, 4, or 5 when Y is absent; or

m is 1, 2, 3, or 4 when Y is NR 10 or 0;

R 1 , R 2 , R 4 , and R 5 are each, independently, selected from the group consisting of H, halogen, and deuterium;

or, alternatively, R 2 and R 5 together with the carbon atoms to which they are attached, form a single bond;

R 3 is selected from the group consisting of H, deuterium, halogen, hydroxyl, and cyano;

or, alternatively, R 3 and R 1 , together with the carbon atoms to which they are attached, form a C 3 -C 5 cycloalkyl;

or, alternatively, R 3 and R 4 , together with the carbon atoms to which they are attached, form a C 3 -C 5 cycloalkyl;

R 6 , R 7 , R 8 , R 9 , and R 11 are each, independently, selected from the group consisting of H, halogen, and deuterium;

R 10 is selected from the group consisting of H, unsubstituted C 1 -C 3 alkyl, and C 1 -C 3 alkyl substituted with one or more halogen atoms; and

each R 12 and R 13 is, independently, selected from the group consisting of H, halogen, deuterium, unsubstituted C 1 -C 3 alkyl, and C 1 -C 3 alkyl substituted with one or more halogen atoms.

69 . The compound of claim 68 , wherein n is 1 or 2.

70 . The compound of claim 68 , wherein ring A is phenyl.

71 . The compound of claim 68 , wherein ring A is pyridinyl.

72 . The compound of claim 68 , wherein Y is O.

73 . The compound of claim 68 , wherein Y is absent.

74 . The compound of claim 68 , wherein T is CR 1 R 2 .

75 . The compound of claim 68 , wherein T is O.

76 . The compound of claim 68 , wherein W is CR 4 R 5 .

77 . The compound of claim 68 , wherein W is O.

78 . The compound of claim 68 , wherein V is CR 3 .

79 . The compound of claim 68 , wherein m is 1 or 2.

80 . A pharmaceutical composition comprising a compound of claim 68 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

81 . A method of treating narcolepsy in a subject in need thereof comprising administering to the subject a compound of claim 68 or a pharmaceutically acceptable salt thereof.

83 . A method of treating cataplexy in a subject in need thereof comprising administering to the subject a compound of claim 68 or a pharmaceutically acceptable salt thereof.