Compounds useful for treating neurodegenerative disorders
The present invention provides compounds of formula I: or a pharmaceutically acceptable salt thereof, wherein R 1 and R 5 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:
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 substituted with 1-4 R 2 groups, or:
two R 1 groups 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 groups are attached, wherein the ring is optionally substituted with 1-3 R 2 groups; or
two R 1 groups are taken together to form a 6-10 membered fused or spiro heterocyclic ring having 0-4 heteroatoms independently selected from oxygen, nitrogen, or sulfur in addition to the nitrogen atom where R 1 groups are attached, wherein the ring is optionally substituted with 1-3 R 2 groups;
each R 2 is independently, halogen, —C(O)N(R) 2 , —N(R) 2 , —OR, —NR 3 S(O) 2 R 3 , oxo, —C(O)OR, C 1-3 alkyl optionally substituted with 1-3 R 3 groups, 3-6 membered cycloalkyl, 3-6 membered saturated heterocyclyl having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur, wherein the cycloalkyl and heterocyclyl are each optionally substituted with 1-3 R 3 , or:
two R 2 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 3 is independently hydrogen, halogen, —OR, 3-6 membered cycloalkyl, —N(R) 2 , C 1-3 alkyl optionally substituted with 1-3 R 4 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, halogen, C 1-3 alkyl optionally substituted with 1-3 —OR groups, 3-6 membered cycloalkyl, or:
two R 4 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 5 is independently hydrogen or C 1-3 alkyl, or:
two R 5 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, 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-a
or a pharmaceutically acceptable salt thereof.
3 . The compound according to claim 1 , wherein one of R 1 is hydrogen.
4 . The compound according to claim 1 , wherein each R 1 is independently a straight or branched C 1-6 alkyl wherein the C 1-6 alkyl is optionally substituted with 1-4 R 2 groups.
5 . The compound according to claim 4 , wherein each R 1 is independently methyl, ethyl, n-propyl, isopropyl, 2,2-dimethylpropyl, 2-methylpropyl, tert-butyl, wherein each R 1 group is optionally substituted with 1-2 R 2 groups.
6 . The compound according to claim 1 , wherein each R 1 is independently a 3-6 membered cycloalkyl.
7 . The compound according to claim 6 , wherein each R 1 is independently cyclohexyl, cyclopentyl, cyclobutyl, or cyclopropyl.
8 . The compound according to claim 1 , wherein each R 1 is independently a 3-6 membered saturated heterocyclyl having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur.
9 . The compound according to claim 8 , wherein each R 1 is independently piperidinyl, pyrrolidinyl, azetidinyl, aziridinyl, tetrahydro-2H-pyranyl, tetrahydrofuranyl, or oxetanyl.
10 . The compound according to claim 1 , wherein two R 1 groups 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 groups are attached, wherein the ring is optionally substituted with 1-3 R 2 groups.
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 one of R 5 is hydrogen.
13 . The compound according to claim 1 , wherein each R 5 is independently C 1-3 alkyl.
14 . The compound according to claim 1 , wherein two R 5 groups on the same nitrogen atom are taken together to form an optionally substituted 3-5 membered carbocyclic ring.
15 . The compound according to claim 14 , wherein —N(R 5 ) 2 is selected from:
16 . The compound according to claim 1 , of formula II:
or a pharmaceutically acceptable salt thereof.
17 . The compound according to claim 16 , wherein one of R 1 is hydrogen.
18 . The compound according to claim 16 , wherein each R 1 is independently methyl, ethyl, n-propyl, isopropyl, 2,2-dimethylpropyl, 2-methylpropyl, tert-butyl, wherein each R 1 group is optionally substituted with 1-2 R 2 groups.
19 . The compound according to claim 16 , wherein each R 1 is independently cyclohexyl, cyclopentyl, cyclobutyl, or cyclopropyl.
20 . The compound according to claim 16 , wherein each R 1 is independently 3-6 membered saturated heterocyclyl having 1-2 heteroatoms independently selected from oxygen, nitrogen, or sulfur.
21 - 51 . (canceled)