IP Library › Granted Patent US 11,185,537
Granted Patent B2
US 11,185,537 · App. 16/504,376 · Granted Nov 30, 2021

3-(5-amino-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof

Inventors: Rohan Eric John Beckwith (Maynard, MA); Simone Bonazzi (Cambridge, MA); Artiom Cernijenko (Cambridge, MA); Fupeng Ma (Melrose, MA); Nathaniel F. Ware (Medford, MA)
Assignee: Novartis AG
A61K31/454A61K31/4545A61K31/498A61P35/00C07D401/04C07D401/14
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 11,185,537
App. No.
16/504,376
Granted
Nov 30, 2021
Kind
B2
Abstract

The present disclosure provides a compound of Formula (I′): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, wherein R a , R b , R x , R 1 , R 2 , X 2 , and q are as defined herein, and methods of making and using same.

Claims (357)

1. A compound of Formula (I′)

wherein:

X 1 and X 2 are each independently H, (C 1 -C 4 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 4 )haloalkyl, (C 1 -C 6 )haloalkoxy, (C 3 -C 7 )cycloalkyl, halogen, CN, —OH, or —NH 2 ;

R x is H or D;

each R a and R b is independently H or D, or R a and R b together with the atom to which they are attached form ═(O);

R 1 is

R 2 is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, or (C 3 -C 6 )cycloalkyl; or

R 2 and R 7 together with the nitrogen atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring;

each R 3 is independently at each occurrence (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, halogen, CN, —OH, or —NH 2 ; or

two R 3 together with the carbon atoms to which they are attached form a (C 3 -C 7 )cycloalkyl or a 4- to 7-membered heterocycloalkyl ring consisting of 1-3 heteroatoms selected from O, N, and S; or two R 3 together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring consisting of 1-3 heteroatoms selected from O, N, and S; or

R 3 and R 7 together with the nitrogen and carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally consisting of 1 to 2 additional heteroatoms selected from O, N, and S, optionally substituted with one to four substituents each independently selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, halogen, —OH, CN, and —NH 2 ;

each R 4 is (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, halogen, —OH, or —NH 2 ;

R 5 is —OR 6 or —NR 7 R 7′ ;

R 6 is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, —C(O)(C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, 5- or 6-membered heterocycloalkyl consisting of 1-3 heteroatoms selected from O, N, and S, (C 6 -C 10 )aryl, or 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three substituents each independently selected from (C 6 -C 10 )aryl and 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S;

R 7 and R 7′ are each independently H, (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )cycloalkyl, 5- or 6-membered heterocycloalkyl consisting of 1-3 heteroatoms selected from O, N, and S, (C 6 -C 10 )aryl, or 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R 8 and wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R 11 ; or

R 7 and R 7′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally consisting of 1 to 2 additional heteroatoms selected from O, N, and S, optionally substituted with one to four R 9 ; or

R 2 and R 7 together with the nitrogen atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring; or

R 3 and R 7 together with the nitrogen and carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally consisting of 1 to 2 additional heteroatoms selected from O, N, and S, optionally substituted with one to four substituents each independently selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, halogen, —OH, CN, and —NH 2 ;

each R 8 is —C(O)OH, (C 3 -C 7 )cycloalkyl, 4- to 7-membered heterocycloalkyl ring consisting of 1-3 heteroatoms selected from O, N, and S, (C 6 -C 10 )aryl, or 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S, wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R 10 ;

each R 9 is independently at each occurrence (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, halogen, —OH, CN, —NR 12 R 13 , or —NH 2 , wherein the alkoxy is optionally substituted with one to three substituents independently selected from (C 3 -C 7 )cycloalkyl, 4- to 7-membered heterocycloalkyl ring consisting of 1-3 heteroatoms selected from O, N, and S, (C 6 -C 10 )aryl, and 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S; or

two R 9 together with the atoms to which they are attached form a (C 5 -C 7 )cycloalkyl or a 5- to 7-membered heterocycloalkyl ring consisting of 1-2 heteroatoms selected from O, N, and S;

each R 10 is independently at each occurrence (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkoxy, halogen, —OH, CN, or —NH 2 ; or

two R 10 together with the atoms to which they are attached form a (C 4 -C 7 )cycloalkyl or a 5- to 7-membered heterocycloalkyl ring consisting of 1-2 heteroatoms selected from O, N, and S optionally substituted with one or more (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, halogen, —OH, CN, or —NH 2 ;

each R 11 is independently at each occurrence (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkoxy, halogen, —OH, CN, or —NH 2 ;

R 12 and R 13 are each independently selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )cycloalkyl, 4- to 7-membered heterocycloalkyl ring consisting of 1-3 heteroatoms selected from O, N, and S, (C 6 -C 10 )aryl, and 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S;

m and m1 are each independently 0, 1 or 2;

n1 is 0, 1, 2, or 3;

n2 and n3 are each independently 1 or 2; and

each s and n is independently 1, 2, or 3, wherein s+n is ≥4;

or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.

2. The compound according to claim 1 , having a Formula (I):

wherein:

R x is H or D;

R 1 is

R 2 is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, or (C 3 -C 6 )cycloalkyl; or

R 2 and R 7 together with the nitrogen atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring;

each R 3 is independently at each occurrence (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, halogen, CN, —OH, or —NH 2 ; or

two R 3 together with the carbon atoms to which they are attached form a (C 3 -C 7 )cycloalkyl or a 4- to 7-membered heterocycloalkyl ring consisting of 1-3 heteroatoms selected from O, N, and S; or two R 3 together when on adjacent carbon atoms form a phenyl or a 5- or 6-membered heteroaryl ring consisting of 1-3 heteroatoms selected from O, N, and S; or

R 3 and R 7 together with the nitrogen and carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally consisting of 1 to 2 additional heteroatoms selected from O, N, and S, optionally substituted with one to four substituents each independently selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, halogen, —OH, CN, and —NH 2 ;

each R 4 is (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )haloalkyl, (C 1 -C 6 )haloalkoxy, halogen, —OH, or —NH 2 ;

R 5 is —OR 6 or —NR 7 R 7′ ;

R 6 is H, (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, —C(O)(C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, 5- or 6-membered heterocycloalkyl consisting of 1-3 heteroatoms selected from O, N, and S, (C 6 -C 10 )aryl, or 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three substituents each independently selected from (C 6 -C 10 )aryl and 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S;

R 7 and R 7′ are each independently H, (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, (C 3 -C 7 )cycloalkyl, 5- or 6-membered heterocycloalkyl consisting of 1-3 heteroatoms selected from O, N, and S, (C 6 -C 10 )aryl, or 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S, wherein the alkyl is optionally substituted with one to three R 8 ; or

R 7 and R 7′ together with the nitrogen atom to which they are attached form a 4- to 7-membered heterocycloalkyl ring optionally consisting of 1 to 2 additional heteroatoms selected from O, N, and S, optionally substituted with one to four R 9 ; or

R 2 and R 7 together with the nitrogen atoms to which they are attached form a 6- or 7-membered heterocycloalkyl ring; or

R 3 and R 7 together with the nitrogen and carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl ring optionally consisting of 1 to 2 additional heteroatoms selected from O, N, and S, optionally substituted with one to four substituents each independently selected from (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, halogen, —OH, CN, and —NH 2 ;

each R8 is (C 3 -C 7 )cycloalkyl, 4- to 7-membered heterocycloalkyl ring consisting of 1-3 heteroatoms selected from O, N, and S, (C 6 -C 10 )aryl, or 5- or 6-membered heteroaryl consisting of 1-3 heteroatoms selected from O, N, and S, wherein the cycloalkyl, heterocycloalkyl, aryl, and heteroaryl are optionally substituted with one to four R 10 ;

each R9 is independently at each occurrence (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, halogen, —OH, CN, or —NH 2 ; or

two R 9 together with the atoms to which they are attached form a (C 5 -C 7 )cycloalkyl or a 5- to 7-membered heterocycloalkyl ring consisting of 1-2 heteroatoms selected from O, N, and S;

each R 10 is independently at each occurrence (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, halogen, —OH, CN, or —NH 2 ; or

two R 10 together with the atoms to which they are attached form a (C 5 -C 7 )cycloalkyl or a 5- to 7-membered heterocycloalkyl ring consisting of 1-2 heteroatoms selected from O, N, and S optionally substituted with one or more (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, halogen, —OH, CN, or —NH 2 ;

m and m1 are each independently 0, 1, or 2;

n1 is 0, 1, 2, or 3; and

each s and n is independently 1, 2, or 3, wherein s+n is ≥4;

or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.

3. The compound according to claim 1 , wherein R 1 is

4. The compound according to claim 1 , wherein n1 is 1 or 2.

5. The compound according to claim 1 , wherein m1 is 0.

6. The compound according to claim 1 , wherein m1 is 2.

7. The compound according to claim 1 , wherein R 1 is

8. The compound according to claim 7 , wherein n is 2 and s is 1 or 2.

9. The compound according to claim 8 , wherein m is 0 or 1.

10. The compound according to claim 1 , having a Formula (Ia), Formula (Ib), Formula (Ia-1), Formula (Ib-1), Formula (Ic), Formula (Id), Formula (Ie), Formula (If), Formula (Ig), Formula (Ih), Formula (Ii), Formula (Ij), Formula (Ic-1), Formula (Id-1), Formula (Ie-1), Formula (If-1), Formula (Ig-1), Formula (Ih-1), Formula (Ii-1), Formula (Ij-1), Formula (Ik), Formula (Il), Formula (Im), Formula (In), Formula (Io), Formula (Ip), Formula (Ik-1), Formula (Il-1), Formula (Im-1), Formula (In-1), Formula (Io-1), or Formula (Ip-1):

or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.

11. The compound according to claim 10 , wherein R 5 is —OR 6 .

12. The compound according to claim 10 , wherein R 5 is —NR 7 R 7′ .

13. The compound according to claim 1 , having a Formula (Iq), Formula (Ir), Formula (Is), Formula (It), Formula (Iq-1), Formula (Ir-1), Formula (Is-1), or Formula (It-1):

or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.

14. The compound according to claim 1 , wherein R 2 is H or methyl.

15. The compound according to claim 1 selected from:

3-(5-(((1S,2S)-2-hydroxycyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-hydroxycyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-hydroxycyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-hydroxycyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-hydroxycyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1R,2R)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1S,2R)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1R,2S)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1S,2S)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl(2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-(benzylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(benzylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(benzylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(benzylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(benzylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-(benzyloxy)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(benzyloxy)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(benzyloxy)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(benzyloxy)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(benzyloxy)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-(benzyl(methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(benzyl(methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(benzyl(methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(benzyl(methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(benzyl(methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-aminocyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-aminocyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-aminocyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-aminocyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-aminocyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-(isopropylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(isopropylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(isopropylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(isopropylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(isopropylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((4aS,8aS)-octahydroquinoxalin-1(2H)-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((4aR,8aS)-octahydroquinoxalin-1(2H)-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((4aR,8aR)-octahydroquinoxalin-1(2H)-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((4aS,8aR)-octahydroquinoxalin-1(2H)-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(octahydroquinoxalin-1(2H)-yl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(ethyl((1S,2S)-2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(ethyl((1S,2R)-2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(ethyl((1R,2R)-2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(ethyl((1R,2S)-2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(ethyl(2-(ethylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1S,2S)-2-(methylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1S,2R)-2-(methylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1R,2R)-2-(methylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1R,2S)-2-(methylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl(2-(methylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(ethyl((1S,2S)-2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione

3-(5-(ethyl((1S,2R)-2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione

3-(5-(ethyl((1R,2R)-2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione

3-(5-(ethyl((1R,2S)-2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(ethyl(2-(ethylamino)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-(benzyl(methyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-((cyclohexylmethyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-((cyclohexylmethyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-((cyclohexylmethyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-((cyclohexylmethyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-((cyclohexylmethyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(1-oxo-5-(((1S,2S)-2-(piperidin-1-yl)cyclopentyl)amino)isoindolin-2-yl)piperidine-2,6-dione;

3-(1-oxo-5-(((1S,2R)-2-(piperidin-1-yl)cyclopentyl)amino)isoindolin-2-yl)piperidine-2,6-dione;

3-(1-oxo-5-(((1R,2R)-2-(piperidin-1-yl)cyclopentyl)amino)isoindolin-2-yl)piperidine-2,6-dione;

3-(1-oxo-5-(((1R,2S)-2-(piperidin-1-yl)cyclopentyl)amino)isoindolin-2-yl)piperidine-2,6-dione;

3-(1-oxo-5-((2-(piperidin-1-yl)cyclopentyl)amino)isoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-(isobutylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(isobutylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(isobutylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(isobutylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(isobutylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1S,6S)-6-(methylamino)cyclohex-3-en-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1S,6R)-6-(methylamino)cyclohex-3-en-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1R,6R)-6-(methylamino)cyclohex-3-en-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1R,6S)-6-(methylamino)cyclohex-3-en-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl(6-(methylamino)cyclohex-3-en-1-yl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

5-(((1R,2R)-2-(dimethylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2S)-2-(dimethylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2S)-2-(dimethylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2R)-2-(dimethylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-((2-(dimethylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2S)-2-aminocyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2R)-2-aminocyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2R)-2-aminocyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2S)-2-aminocyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-((2-aminocyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2S)-2-(ethylamino)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2R)-2-(ethylamino)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2R)-2-(ethylamino)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2S)-2-(ethylamino)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-((2-(ethylamino)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2S)-2-(methylamino)cycloheptyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2R)-2-(methylamino)cycloheptyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2R)-2-(methylamino)cycloheptyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2S)-2-(methylamino)cycloheptyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(2-(methylamino)cycloheptyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2S)-2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2R)-2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2R)-2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2S)-2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,6S)-6-(methylamino)cyclohex-3-en-1-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,6R)-6-(methylamino)cyclohex-3-en-1-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,6R)-6-(methylamino)cyclohex-3-en-1-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,6S)-6-(methylamino)cyclohex-3-en-1-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(6-(methylamino)cyclohex-3-en-1-yl)amino)isoindoline-1,3-dione;

3-(5-(((1S,2S)-2-aminocyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-aminocyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-aminocyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-aminocyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-aminocyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2S)-2-(methylamino)cyclopentyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2R)-2-(methylamino)cyclopentyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2R)-2-(methylamino)cyclopentyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2S)-2-(methylamino)cyclopentyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(2-(methylamino)cyclopentyl)amino)isoindoline-1,3-dione;

5-(((1S,2S)-2-(benzylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2R)-2-(benzylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2R)-2-(benzylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2S)-2-(benzylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-((2-(benzylamino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2S)-2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2R)-2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2R)-2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2S)-2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(2-(((1-(trifluoromethyl)cyclopropyl)methyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2S)-2-((pyridin-3-ylmethyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2R)-2-((pyridin-3-ylmethyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2R)-2-((pyridin-3-ylmethyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2S)-2-((pyridin-3-ylmethyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(2-((pyridin-3-ylmethyl)amino)cyclohexyl)amino)isoindoline-1,3-dione;

((1S,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)(methyl)amino)cyclohexyl)glycine

((1R,2S)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)(methyl)amino)cyclohexyl)glycine

((1R,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)(methyl)amino)cyclohexyl)glycine

((1S,2R)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)(methyl)amino)cyclohexyl)glycine

(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)(methyl)amino)cyclohexyl)glycine

5-(((1S,2S)-2-(dimethylamino)cyclohexyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2R)-2-(dimethylamino)cyclohexyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2R)-2-(dimethylamino)cyclohexyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2S)-2-(dimethylamino)cyclohexyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-((2-(dimethylamino)cyclohexyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(3-(methylamino)bicyclo[2.2.1]hept-5-en-2-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((2S,3S)-3-(methylamino)bicyclo[2.2.1]hept-5-en-2-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((2S,3R)-3-(methylamino)bicyclo[2.2.1]hept-5-en-2-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((2R,3R)-3-(methylamino)bicyclo[2.2.1]hept-5-en-2-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((2R,3S)-3-(methylamino)bicyclo[2.2.1]hept-5-en-2-yl)amino)isoindoline-1,3-dione;

3-(4-fluoro-5-(methyl((1S,2S)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(4-fluoro-5-(methyl((1S,2R)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(4-fluoro-5-(methyl((1R,2R)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(4-fluoro-5-(methyl((1R,2S)-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(4-fluoro-5-(methyl(2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(methyl((1S,2S)-2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(methyl((1S,2R)-2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(methyl((1R,2R)-2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(methyl((1R,2S)-2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-fluoro-6-(methyl(2-(methylamino)cyclohexyl)amino)isoindoline-1,3-dione;

3-(5-(((1S,2S)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2S)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2R)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2R)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2S)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-((2-(3-ethoxyazetidin-1-yl)cyclohexyl)(methyl)amino)isoindoline-1,3-dione;

3-(5-(((1S,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

5-(((1S,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-((2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

3-(5-(((1S,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

5-(((1S,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2R)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2S)-2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-((2-(((3,3-difluorocyclobutyl)methyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

3-(5-(methyl((1S,2S)-2-(piperidin-1-yl)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1S,2R)-2-(piperidin-1-yl)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1R,2R)-2-(piperidin-1-yl)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl((1R,2S)-2-(piperidin-1-yl)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(methyl(2-(piperidin-1-yl)cyclopentyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2S)-2-(piperidin-1-yl)cyclopentyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2R)-2-(piperidin-1-yl)cyclopentyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2R)-2-(piperidin-1-yl)cyclopentyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2S)-2-(piperidin-1-yl)cyclopentyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(2-(piperidin-1-yl)cyclopentyl)amino)isoindoline-1,3-dione;

5-(((1S,2S)-2-(diethylamino)cyclopentyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2R)-2-(diethylamino)cyclopentyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2R)-2-(diethylamino)cyclopentyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2S)-2-(diethylamino)cyclopentyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-((2-(diethylamino)cyclopentyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2S)-2-(3-ethoxyazetidin-1-yl)cyclopentyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2R)-2-(3-ethoxyazetidin-1-yl)cyclopentyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2R)-2-(3-ethoxyazetidin-1-yl)cyclopentyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2S)-2-(3-ethoxyazetidin-1-yl)cyclopentyl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-((2-(3-ethoxyazetidin-1-yl)cyclopentyl)(methyl)amino)isoindoline-1,3-dione;

5-(((1S,2S)-1-amino-2,3-dihydro-1H-inden-2-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2S)-1-amino-2,3-dihydro-1H-inden-2-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2R)-1-amino-2,3-dihydro-1H-inden-2-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2R)-1-amino-2,3-dihydro-1H-inden-2-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-((1-amino-2,3-dihydro-1H-inden-2-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2S)-1-(ethylamino)-2,3-dihydro-1H-inden-2-yl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2S)-1-(ethylamino)-2,3-dihydro-1H-inden-2-yl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2R)-1-(ethylamino)-2,3-dihydro-1H-inden-2-yl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2R)-1-(ethylamino)-2,3-dihydro-1H-inden-2-yl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-((1-(ethylamino)-2,3-dihydro-1H-inden-2-yl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2S)-1-(methylamino)-2,3-dihydro-1H-inden-2-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2S)-1-(methylamino)-2,3-dihydro-1H-inden-2-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2R)-1-(methylamino)-2,3-dihydro-1H-inden-2-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2R)-1-(methylamino)-2,3-dihydro-1H-inden-2-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(1-(methylamino)-2,3-dihydro-1H-inden-2-yl)amino)isoindoline-1,3-dione;

5-(((1S,2S)-2-amino-2,3-dihydro-1H-inden-1-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2R)-2-amino-2,3-dihydro-1H-inden-1-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2R)-2-amino-2,3-dihydro-1H-inden-1-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1R,2S)-2-amino-2,3-dihydro-1H-inden-1-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-((2-amino-2,3-dihydro-1H-inden-1-yl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2S)-2-(methylamino)-2,3-dihydro-1H-inden-1-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2R)-2-(methylamino)-2,3-dihydro-1H-inden-1-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2R)-2-(methylamino)-2,3-dihydro-1H-inden-1-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1R,2S)-2-(methylamino)-2,3-dihydro-1H-inden-1-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(methyl(2-(methylamino)-2,3-dihydro-1H-inden-1-yl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2S)-2-(ethylamino)-2,3-dihydro-1H-inden-1-yl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1S,2R)-2-(ethylamino)-2,3-dihydro-1H-inden-1-yl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2R)-2-(ethylamino)-2,3-dihydro-1H-inden-1-yl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-(((1R,2S)-2-(ethylamino)-2,3-dihydro-1H-inden-1-yl)(methyl)amino)isoindoline-1,3-dione;

2-(2,6-dioxopiperidin-3-yl)-5-((2-(ethylamino)-2,3-dihydro-1H-inden-1-yl)(methyl)amino)isoindoline-1,3-dione;

3-(4-amino-5-(((1S,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(4-amino-5-(((1S,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(4-amino-5-(((1R,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(4-amino-5-(((1R,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(4-amino-5-((2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-4-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-4-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-4-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-4-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-4-hydroxy-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

4-amino-5-(((1S,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

4-amino-5-(((1S,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

4-amino-5-(((1R,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

4-amino-5-(((1R,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

4-amino-5-((2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione;

5-(((1S,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)-4-hydroxyisoindoline-1,3-dione;

5-(((1S,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)-4-hydroxyisoindoline-1,3-dione;

5-(((1R,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)-4-hydroxyisoindoline-1,3-dione;

5-(((1R,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)-4-hydroxyisoindoline-1,3-dione;

5-((2-((4,4-difluorocyclohexyl)amino)cyclohexyl)(methyl)amino)-2-(2,6-dioxopiperidin-3-yl)-4-hydroxyisoindoline-1,3-dione;

3-(5-(((1S,2S)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-(3-ethoxyazetidin-1-yl)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-(3-ethoxyazetidin-1-yl)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1S,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2R)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-(((1R,2S)-2-((4,4-difluorocyclohexyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

3-(5-((2-((4,4-difluorocyclohexyl)amino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione;

rac-trans-2-(2,6-dioxopiperidin-3-yl)-5-(octahydroquinoxalin-1(2H)-yl)isoindoline-1,3-dione;

trans-3-(5-(methyl(-2-(methylamino)cyclohexyl)amino)-1-oxoisoindolin-2-yl)piperidine-2,6-dione; and

2-(2,6-dioxopiperidin-3-yl)-5-(methyl((1S,2S)-2-(methylamino)cyclopentyl)amino) isoindoline-1,3-dione;

or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof.

16. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, and a pharmaceutically acceptable carrier or excipient.

17. The pharmaceutical composition of claim 16 further comprising at least one additional pharmaceutical agent.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2019
From: CERNIJENKO, ARTIOM; BONAZZI, SIMONE; BECKWITH, ROHAN ERIC JOHN
To: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
Reel/Frame 049746/0520 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2019
From: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
To: NOVARTIS AG
Reel/Frame 049746/0537 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2019
From: CERNIJENKO, ARTIOM; BONAZZI, SIMONE; BECKWITH, ROHAN ERIC JOHN; WARE, NATHANIEL F.; MA, FUPENG
To: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
Reel/Frame 049746/0542 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2019
From: NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH, INC.
To: NOVARTIS AG
Reel/Frame 049746/0554 →
Continuity (2)
Provisional Application 62695922 · Jul 10, 2018
Related Publication 20200016143A1 · Jan 16, 2020
Cited By (2)
US 12,358,887 US 12,606,636