Compounds useful for treating neurodegenerative disorders
The present invention provides compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein L and Ring A are 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:
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;
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 —OH 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; and
each R is independently hydrogen, 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 of claim 1 , wherein Ring A is selected from
3 . The compound according to claim 1 , wherein R 1 is H.
4 . The compound according to claim 1 , wherein R 1 is a straight or branched C 1-6 alkyl wherein the C 1-6 alkyl is optionally substituted with 1-4 R 3 groups.
5 . The compound according to claim 4 , wherein R 1 is methyl, ethyl, n-propyl, isopropyl, 2,2-dimethylpropyl, 2-methylpropyl, tert-butyl, wherein each R 1 group is optionally substituted with 1-2 R 3 groups.
6 . The compound according to claim 1 , wherein R 1 is a 3-6 membered cycloalkyl.
7 . The compound according to claim 6 , wherein R 1 is cyclohexyl, cyclopentyl, cyclobutyl, or cyclopropyl.
8 . The compound according to claim 1 , wherein R 1 is selected from 3-6 membered saturated heterocyclyl having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur.
9 . The compound according to claim 8 , wherein R 1 is selected from:
10 . The compound according to claim 1 , 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.
11 . The compound according to claim 10 , wherein the 3-7 membered heterocyclic ring is selected from:
12 . The compound according to claim 1 , wherein said compound is of formula I-a
or a pharmaceutically acceptable salt thereof; wherein Ring A is selected from
13 . The compound according to claim 1 , wherein said compound is of formula II
or a pharmaceutically acceptable salt thereof; wherein Ring A is selected from
14 . The compound according to claim 13 , wherein Ring A is
15 . The compound according to claim 13 , wherein Ring A is
16 . The compound according to claim 13 , wherein Ring A is
17 . The compound according to claim 13 , wherein R 1 is a straight or branched C 1-6 alkyl wherein the C 1-6 alkyl is optionally substituted with 1-4 R 3 groups.
18 . The compound according to claim 17 , wherein R 1 is methyl, ethyl, n-propyl, isopropyl, 2,2-dimethylpropyl, 2-methylpropyl, tert-butyl, wherein each R 1 group is optionally substituted with 1-2 R 3 groups.
19 . The compound according to claim 13 , wherein R 1 is a 3-6 membered cycloalkyl.
20 . The compound according to claim 19 , wherein R 1 is cyclohexyl, cyclopentyl, cyclobutyl, or cyclopropyl.
21 - 45 . (canceled)