IP Library › Patent Application 18649114
Patent Application
App. No. 18/649,114

COMPOUNDS AND USES THEREOF

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Quick Facts
Patent No.
US None
App. No.
18/649,114
Abstract

The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.

Claims (80)

1 . A compound, or pharmaceutically acceptable salt thereof, having the structure of Formula Ia:

wherein B is absent or has the structure:

the dashed line represents an optional double bond;

Het is —C(O)NH— or an optionally substituted optionally substituted C 2 -C 9 heteroaryl;

m is 0 or 1;

n is 0, 1, or 2;

o is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

p and r are, independently, 0 or 1;

X 1 and X 2 are each, independently, N or CR 6 ;

L 1 is —O—, —SO 2 —, NR 2 , optionally substituted C 1 -C 6 alkylene, optionally substituted C 1 -C 6 alkenylene, optionally substituted C 1 -C 6 heteroalkylene, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted C 2 -C 9 heteroaryl, or optionally substituted C 2 -C 9 heterocycle;

L 2 is absent, —O—, —SO 2 —, NR 2 , or —CR 2 R 3 —;

R 1 is optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 6 -C 10 aryl C 1 -C 6 alkyl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted C 3 -C 7 cycloalkyl C 1 -C 6 alkyl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 9 heteroaryl C 1 -C 6 alkyl, optionally substituted C 2 -C 9 heterocycle, or optionally substituted C 2 -C 9 heterocycle C 1 -C 6 alkyl;

R 2 and R 3 are each, independently, hydrogen, optionally substituted C 1 -C 6 alkyl, or combine with the carbon to which they are attached to form a carbonyl or an optionally substituted C 3 -C 7 cycloalkyl;

each R 4 is, independently, halogen, hydroxyl, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or two R 4 combine with the carbon two which they are attached to form a carbonyl or optionally substituted C 3 -C 7 cycloalkyl;

R 5 is optionally substituted C 6 -C 10 aryl, optionally substituted C 2 -C 9 heteroaryl, optionally substituted C 2 -C 9 heterocycle, or optionally substituted C 2 -C 9 heteroaryl C 1 -C 6 alkyl; and

each R 6 is, independently, hydrogen, halogen, hydroxy, optionally substituted C 1 -C 6 heteroalkyl, or optionally substituted C 1 -C 6 alkyl.

2 . (canceled)

3 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein B has the structure of Formula Ib:

4 . The compound, or pharmaceutically acceptable salt thereof, of claim 3 , wherein X 1 is N and X 2 is CR 6 .

5 . The compound, or pharmaceutically acceptable salt thereof, of claim 3 , wherein o is 0, 1, or 2.

6 - 18 . (canceled)

19 . The compound, or pharmaceutically acceptable salt thereof, of claim 4 , wherein B has the structure:

20 . The compound, or pharmaceutically acceptable salt thereof, of claim 3 , wherein X 1 is CR 6 and X 2 is N.

21 . The compound, or pharmaceutically acceptable salt thereof, of claim 20 , wherein o is 0, 1, or 2.

22 - 35 . (canceled)

36 . The compound, or pharmaceutically acceptable salt thereof, of claim 3 , wherein X 1 is N and X 2 is N.

37 . The compound, or pharmaceutically acceptable salt thereof, of claim 36 , wherein o is 0, 1, or 2.

37 - 44 . (canceled)

45 . The compound, or pharmaceutically acceptable salt thereof, of claim 3 , wherein X 1 is CR 6 and X 2 is CR 6 .

46 . The compound, or pharmaceutically acceptable salt thereof, of claim 45 , wherein o is 0, 1, or 2.

47 - 60 . (canceled)

61 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein B has the structure of Formula Ic:

62 - 64 . (canceled)

65 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein B has the structure of Formula Id:

66 - 68 . (canceled)

69 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein B has the structure of Formula Ie:

70 - 72 . (canceled)

73 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein B has the structure of Formula If:

74 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein Het is —C(O)NH— or:

wherein X 3 is O or S.

75 - 76 . (canceled)

77 . The compound, or pharmaceutically acceptable salt thereof, of claim 74 , wherein Het is

78 - 104 . (canceled)

105 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein R 1 is optionally substituted C 1 -C 6 alkyl.

106 - 120 . (canceled)

121 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein R 5 is optionally substituted C 6 -C 10 aryl.

122 . The compound, or pharmaceutically acceptable salt thereof, of claim 121 , wherein R 5 is phenyl, 3,4-dimethoxy-phenyl, 3-methoxy-4-ethoxy-phenyl, 3,5-dimethoxy-phenyl, 3-methoxy-4-cyclopropoxy-phenyl, 3-methoxy-4-trifluoromethoxy-phenyl, 3-isopropoxy-4-methoxy-phenyl,

123 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein R 5 is optionally substituted C 2 -C 9 heteroaryl.

124 . The compound, or pharmaceutically acceptable salt thereof, of claim 123 , wherein R 5 is

125 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein R 5 is an optionally substituted C 2 -C 9 heterocycle.

126 . The compound, or pharmaceutically acceptable salt thereof, of claim 125 , wherein R 5 is

127 . The compound, or pharmaceutically acceptable salt thereof, of claim 1 , wherein R 5 is optionally substituted C 2 -C 9 heteroaryl C 1 -C 6 alkyl.

128 . The compound, or pharmaceutically acceptable salt thereof, of claim 127 , wherein R 5 is

129 . A compound, or a pharmaceutically acceptable salt thereof, having the structure of Formula I:

wherein Het is an optionally substituted optionally substituted C 2 -C 9 heteroaryl;

m is 0 or 1;

n is 0, 1, or 2;

o is 0, 1, 2, 3, 4, 5, 6, 7, or 8;

X 1 and X 2 are each, independently, N or CR 4 ;

L is optionally substituted C 1 -C 6 alkylene, optionally substituted C 1 -C 6 alkenylene, optionally substituted C 1 -C 6 heteroalkylene, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted C 2 -C 9 heteroaryl, or optionally substituted C 2 -C 9 heterocycle;

R 1 is optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 3 -C 7 cycloalkyl, optionally substituted C 2 -C 9 heteroaryl, or optionally substituted C 2 -C 9 heterocycle;

R 2 and R 3 are each, independently, hydrogen, optionally substituted C 1 -C 6 alkyl, or combine with the carbon to which they are attached to form a carbonyl;

each R 4 is, independently, halogen, hydroxyl, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 heteroalkyl, or two R 4 combine with the carbon two which they are attached to form a carbonyl;

R 5 is optionally substituted C 6 -C 10 aryl or optionally substituted C 2 -C 9 heteroaryl; and

each R 6 is, independently, hydrogen or optionally substituted C 1 -C 6 alkyl.

130 . The compound, or a pharmaceutically acceptable salt thereof, of claim 129 , wherein R 2 and R 3 combine with the carbon to which they are attached to form a carbonyl.

131 . The compound, or a pharmaceutically acceptable salt thereof, of claim 129 having the structure of Formula II or IIa:

wherein X 3 is O or S.

132 - 136 . (canceled)

137 . The compound, or pharmaceutically acceptable salt thereof, of claim 136 , wherein the compound has the structure of Formula III or IIIa:

wherein p is 1, 2, 3, 4, or 5;

each R 7 is, independently, halogen, nitrile, OR 8 , or optionally substituted C 1 -C 6 alkyl; and

each R 8 is, independently, hydrogen or optionally substituted C 1 -C 6 alkyl.

138 . The compound, or pharmaceutically acceptable salt thereof, of claim 137 , wherein the compound has the structure of Formula IV or IVa:

139 - 146 . (canceled)

147 . The compound, or pharmaceutically acceptable salt thereof, of claim 146 , wherein the compound has the structure of Formula V or Va:

wherein q is 1, 2, 3, 4, or 5; and

R 9 is halogen or optionally substituted C 1 -C 6 alkyl.

148 . The compound, or pharmaceutically acceptable salt thereof, of claim 147 , wherein the compound has the structure of Formula VI or VIa:

149 - 165 . (canceled)