Compounds useful for treating neurodegenerative disorders
The present invention provides compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein R x is as defined and described herein, compositions thereof, and methods of using the same.
1 . A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R x is -L-Ring A or -L′-R y ;
Ring A is selected from:
each m is independently 0, 1, 2, 3, or 4;
L is a covalent bond, or a straight or branched C 1-5 saturated or unsaturated, straight or branched, divalent hydrocarbon chain;
each R 1 is independently hydrogen, straight or branched C 1-6 alkyl, 3-6 membered cycloalkyl, or 3-6 membered saturated heterocyclyl having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur, wherein each R 1 is optionally and independently substituted with 1-4 R 3 groups, or:
R 1 and an R 2 group on a carbon adjacent to R 1 are taken together to form an optionally substituted 3-7 membered heterocyclic ring having 0-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur in addition to the nitrogen atom where R 1 is attached; or:
R 1 and an R 2 group on a carbon non-adjacent to R 1 are taken together with their intervening atoms to form an optionally substituted 4-7 membered bridged heterocyclic ring having 0-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur in addition to the nitrogen atom where R 1 is attached;
L′ is a straight or branched C 2-5 saturated or unsaturated, straight or branched, divalent hydrocarbon chain;
R y is —N(R′) 2 , wherein each R′ is independently selected from hydrogen or C 1-6 aliphatic optionally substituted with 1-2 groups independently selected from halogen, —OR, or —N(R) 2 , or:
two R′ groups on the same nitrogen atom are taken together with the nitrogen atom to form a 3-8 membered saturated or partially unsaturated heterocyclic ring optionally having one heteroatom, in addition to the nitrogen, selected from nitrogen, oxygen, or sulfur, wherein the ring is optionally substituted with 1-2 groups independently selected from halogen, —OR, or —N(R) 2 ;
each R 2 is independently R, deuterium, —OR, oxo, or:
two R 2 groups on the same carbon are taken together to form an optionally substituted spiro-fused 3-7 membered saturated carbocyclic or a 3-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur; or:
two R 2 groups on adjacent carbon atoms are taken together to form an optionally substituted 3-7 membered saturated carbocyclic or a 3-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur; or:
two R 2 groups on non-adjacent carbon atoms are taken together with their intervening atoms to form an optionally substituted 4-7 membered bridged saturated carbocyclic or a 4-7 membered bridged heterocyclic ring having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur;
each R 3 is independently R, halogen, —C(O)N(R) 2 , —OR, C 1-3 alkyl optionally substituted with one or two —OR groups, or:
two R 3 groups on the same carbon atom are taken together to form an optionally substituted 3-6 membered saturated carbocyclic or a 3-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur;
each R 4 is independently hydrogen or C 1-3 alkyl, or:
two R 4 groups on the same nitrogen atom are taken together to form an optionally substituted 3-5 membered heterocyclic ring; and
each R is independently hydrogen or C 1-4 aliphatic, or:
two R groups on the same nitrogen atom are taken together to form an optionally substituted 4-8 membered saturated or partially unsaturated ring.
2 . The compound according to claim 1 , wherein said compound is of formula I-i
or a pharmaceutically acceptable salt thereof.
3 . The compound according to claim 2 , wherein Ring A is selected from
4 . The compound according to claim 2 , wherein each R 1 is hydrogen.
5 . The compound according to claim 2 , wherein each R 1 is independently straight or branched C 1-6 alkyl wherein the C 1-6 alkyl is optionally and independently substituted with 1-4 R 3 groups.
6 . The compound according to claim 2 , wherein each R 1 is independently 3-6 membered cycloalkyl optionally and independently substituted with 1-4 R 3 groups.
7 . The compound according to claim 2 , wherein each R 1 is independently 3-6 membered saturated heterocyclyl having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur.
8 . The compound according to claim 2 , wherein R 1 and an R 2 group on a carbon adjacent to R 1 are taken together to form a 3-7 membered heterocyclic ring having 0-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur in addition to the nitrogen atom where R 1 is attached.
9 . The compound according to claim 2 , wherein each R 4 is hydrogen.
10 . The compound according to claim 2 , wherein each R 4 is independently C 1-3 alkyl.
11 . The compound according to claim 2 , wherein two R 4 groups on the same nitrogen atom are taken together to form an optionally substituted 3-5 membered heterocyclic ring.
12 . The compound according to claim 2 , of formula II:
or a pharmaceutically acceptable salt thereof.
13 . The compound according to claim 12 , wherein Ring A is:
14 . The compound according to claim 12 , wherein Ring A is:
15 . The compound according to claim 12 , wherein Ring A is:
16 . The compound according to claim 12 , wherein each R 1 is hydrogen.
17 . The compound according to claim 12 , wherein each R 1 is independently straight or branched hexyl, straight or branched pentyl, straight or branched butyl, straight or branched propyl, ethyl or methyl; substituted with 1-4 R 3 groups.
18 . The compound according to claim 12 , wherein each R 1 is cyclohexyl, cyclopentyl, cyclobutyl, or cyclopropyl.
19 . The compound according to claim 12 , wherein each R 1 is
20 . The compound according to claim 12 , wherein each R 2 is hydrogen.
21 - 61 . (canceled)