Muscarinic acetylcholine M

1. A compound of Formula (I′):

wherein:

X is —CH 2 CH 2 —, —CH 2 O—, —CH 2 CH 2 O—, —O—, —N(R 14 )—, S(O) 2 , —CH 2 N(R 14 )—, or —CH 2 CH 2 N(R 14 )—;

Y is a bond, —C(R 16 )(R 17 )—, or —N(R 15 )—;

Z is —N— or —C(H)—;

R 1 is

wherein ring A is a heteroaryl ring optionally substituted with halogen, —CN, —N(R 22 ) 2 , C 1-6 alkyl, C 1-6 alkyl-OH, C 1-6 alkoxy, C 1-6 haloalkyl, or C 1-6 haloalkoxy, wherein the heteroaryl ring contains 1 or 2 heteroatoms selected from the group consisting of O, N, or S;

each R 2 is independently selected from H, halogen, and C 1-6 alkyl;

each R 3 is independently selected from H, halogen, and C 1-6 alkyl;

R 4 , R 6 , R 8 , and R 10 are each independently selected from H and C 1-6 alkyl;

R 5 , R 7 , R 9 , and R 11 are each independently selected from H and C 1-6 alkyl; and wherein: (i) R 7 and R 11 combine to form a bridged C 3-15 cycloalkyl or bridged 3 to 18 membered heterocycloalkyl; or (ii) R 5 and R 9 combine to form a bridged C 3-15 cycloalkyl or bridged 3 to 18 membered heterocycloalkyl; or (iii) R 7 and R 9 combine to form a bridged C 4-15 cycloalkyl or bridged 4 to 18 membered heterocycloalkyl;

R 12 is

each R 13 is independently selected from halogen, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy;

R 14 is H, C 1-6 alkyl, C 3-6 cycloalkyl, or C 2-9 heterocycloalkyl; or R 14 and one R 3 combine to form a 4-, 5-, or 6-membered heterocycloalkyl ring;

R 15 is H or C 1-6 alkyl; or R 15 and one R 3 combine to form a 4-, 5-, or 6-membered heterocycloalkyl ring;

R 16 is H or C 1-6 alkyl;

R 17 is H or C 1-6 alkyl; or R 17 and one R 3 combine to form a 3-, 4-, 5-, or 6-membered cycloalkyl ring;

each R 18 and each R 19 is independently selected from halogen, —CN, —N(R 22 ) 2 , C 1-6 alkyl, C 3-6 cycloalkyl, hydroxy, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, and phenyl;

R 20 and R 21 combine to form a 5- or 6-membered cycloalkyl ring or a 5-membered heterocycloalkyl ring;

each R 22 is independently selected from H and C 1-6 alkyl;

m is 0, 1, 2, or 3;

n is 1, 2, 3, 4, or 5;

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

q is 0, 1, or 2;

or a pharmaceutically acceptable salt or solvate thereof.

2. A compound of Formula (I):

wherein:

X is —CH 2 CH 2 —, —CH 2 O—, —CH 2 CH 2 O—, —O—, —N(R 14 )—, S(O) 2 , —CH 2 N(R 14 )—, or —CH 2 CH 2 N(R 14 )—;

Y is a bond, —C(R 16 )(R 17 )—, or —N(R 15 )—;

Z is —N— or —C(H)—;

R 1 is

wherein ring A is a heteroaryl ring optionally substituted with halogen, —CN, —N(R 22 ) 2 , C 1-6 alkyl, C 1-6 alkyl-OH, C 1-6 alkoxy, C 1-6 haloalkyl, or C 1-6 haloalkoxy, wherein the heteroaryl ring contains 1 or 2 heteroatoms selected from the group consisting of O, N, or S;

each R 2 is independently selected from H and C 1-6 alkyl;

each R 3 is independently selected from H and C 1-6 alkyl;

R 4 , R 6 , R 8 , and R 10 are each independently selected from H and C 1-6 alkyl;

R 5 , R 7 , R 9 , and R 11 are each independently selected from H and C 1-6 alkyl; and wherein: (i) R 7 and R 11 combine to form a bridged C 3-15 cycloalkyl or bridged 3 to 18 membered heterocycloalkyl; or (ii) R 5 and R 9 combine to form a bridged C 3-15 cycloalkyl or bridged 3 to 18 membered heterocycloalkyl; or (iii) R 7 and R 9 combine to form a bridged C 4-15 cycloalkyl or bridged 4 to 18 membered heterocycloalkyl;

R 12 is

each R 13 is independently selected from halogen, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy;

R 14 is H or C 1-6 alkyl; or R 14 and one R 3 combine to form a 4-, 5-, or 6-membered heterocycloalkyl ring;

R 15 is H or C 1-6 alkyl; or R 15 and one R 3 combine to form a 4-, 5-, or 6-membered heterocycloalkyl ring;

R 16 is H or C 1-6 alkyl;

R 17 is H or C 1-6 alkyl; or R 17 and one R 3 combine to form a 3-, 4-, 5-, or 6-membered cycloalkyl ring;

each R 18 and each R 19 is independently selected from halogen, —CN, C 1-6 alkyl, hydroxy, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy;

R 20 and R 21 combine to form a 5- or 6-membered cycloalkyl ring or a 5-membered heterocycloalkyl ring;

each R 22 is independently selected from H and C 1-6 alkyl;

m is 0, 1, 2, or 3;

n is 1, 2, 3, 4, or 5;

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

q is 0, 1, or 2;

or a pharmaceutically acceptable salt or solvate thereof.

3. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is

4. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein m is 0.

5. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (Ia) or Formula (Ib):

6. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 12 is

7. A compound of Formula (II):

wherein:

X is —CH 2 CH 2 —, —CH 2 O—, —CH 2 CH 2 O—, —O—, —N(R 14 )—,—S(O) 2 —, —CH 2 N(R 14 )—, or —CH 2 CH 2 N(R 14 )—;

Y is a bond, —C(R 16 )(R 17 )—, or —N(R 15 )—;

Z is —N— or —C(H)—;

R 1 is

wherein ring A is a heteroaryl ring optionally substituted with halogen, —CN, —N(R 22 ) 2 , C 1-6 alkyl, C 1-6 alkyl-OH, C 1-6 alkoxy, C 1-6 haloalkyl, or C 1-6 haloalkoxy, wherein the heteroaryl ring contains 1 nitrogen atom and 0 or 1 oxygen or sulfur atoms;

each R 2 is independently selected from H and C 1-6 alkyl;

each R 3 is independently selected from H and C 1-6 alkyl;

R 4 , R 6 , R 8 , and R 10 are each independently selected from H and C 1-6 alkyl;

R 5 , R 7 , R 9 , and R 11 are each independently selected from H and C 1-6 alkyl; and wherein: (i) R 7 and R 11 combine to form a bridged C 3-15 cycloalkyl or bridged 3 to 18 membered heterocycloalkyl; or (ii) R 5 and R 9 combine to form a bridged C 3-15 cycloalkyl or bridged 3 to 18 membered heterocycloalkyl; or (iii) R 7 and R 9 combine to form a bridged C 4-15 cycloalkyl or bridged 4 to 18 membered heterocycloalkyl;

R 12 is

each R 13 is independently selected from halogen, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy;

R 14 is H or C 1-6 alkyl; or R 14 and one R 3 combine to form a 4-, 5-, or 6-membered heterocycloalkyl ring;

R 15 is H or C 1-6 alkyl; or R 15 and one R 3 combine to form a 4-, 5-, or 6-membered heterocycloalkyl ring;

R 16 is H or C 1-6 alkyl;

R 17 is H or C 1-6 alkyl; or R 17 and one R 3 combine to form a 3-, 4-, 5-, or 6-membered cycloalkyl ring;

each R 18 is independently selected from halogen, —CN, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, and C 1-6 haloalkoxy;

each R 22 is independently selected from H and C 1-6 alkyl;

m is 0, 1, 2, or 3;

n is 1, 2, 3, 4, or 5;

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

v is 0, 1, 2, 3, 4, or 5;

or a pharmaceutically acceptable salt or solvate thereof.

8. The compound of claim 7 , or a pharmaceutically acceptable salt or solvate thereof, wherein R 1 is

9. The compound of claim 7 , or a pharmaceutically acceptable salt or solvate thereof, having the structure of Formula (IIa) or Formula (IIb):

10. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein (a) X is —CH 2 CH 2 —, —CH 2 O—, —CH 2 N(H)—, or —S(O) 2 —; and (b) Y is a bond.

11. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein each R 2 and each R 3 is H.

12. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein

(a) X is —O—, Y is —C(R 16 )(R 17 )—, and R 17 and one R 3 combine to form a 3- or 4-membered cycloalkyl ring;

(b) X is —N(R 14 )—; Y is bond; and R 14 and one R 3 combine to form a 4-, 5-, or 6-membered heterocycloalkyl ring; or

(c) X is —O—; Y is —N(R 15 )—; and R 15 and one R 3 combine to form a 4-, 5-, or 6-membered heterocycloalkyl ring.

13. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, wherein

(a) R 4 , R 6 , R 8 , and R 10 are H;

(b) R 5 and R 9 are H, and R 7 and R 11 combine to form a bridged C 3-15 cycloalkyl or bridged 3 to 18 membered heterocycloalkyl;

(c) R 5 and R 11 are H, and R 7 and R 9 combine to form a bridged C 4-15 cycloalkyl or bridged 4 to 18 membered heterocycloalkyl; or

(d) R 7 and R 11 are H, and R 5 and R 9 combine to form a bridged C 3-15 cycloalkyl or bridged 3 to 18 membered heterocycloalkyl.

14. A compound selected from:

and

or a pharmaceutically acceptable salt or solvate thereof.

15. A compound selected from:

and

or a pharmaceutically acceptable salt or solvate thereof.

16. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

17. A method of treating multiple sclerosis, Parkinson's disease, dystonia, and fragile X syndrome in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof.

18. The compound of claim 1 , wherein: (i) R 7 and R 11 combine to form a bridged C 5-15 cycloalkyl or bridged 5 to 15 membered heterocycloalkyl; or (ii) R 5 and R 9 combine to form a bridged C 5-15 cycloalkyl or bridged 5 to 15 membered heterocycloalkyl; or (iii) R 7 and R 9 combine to form a bridged C 5-15 cycloalkyl or bridged 5 to 15 membered heterocycloalkyl.

19. The compound of claim 1 , wherein: (i) R 7 and R 11 combine to form a bridged C 5-7 cycloalkyl or bridged 5 to 7 membered heterocycloalkyl; or (ii) R 5 and R 9 combine to form a bridged C 5-7 cycloalkyl or bridged 5 to 7 membered heterocycloalkyl; or (iii) R 7 and R 9 combine to form a bridged C 5-7 cycloalkyl or bridged 5 to 7 membered heterocycloalkyl.