US2022298172A1PendingUtilityA1
Protein-targeting compounds and pharmaceutical compositions thereof, and their therapeutic applications
Est. expiryMay 24, 2039(~12.9 yrs left)· nominal 20-yr term from priority
Inventors:Kyle W.H. ChanPaul E. ErdmanAparajita Hoskote ChourasiaLeah FungDavid Aaron HechtImelda LamFrank MercurioRobert SullivanEduardo Torres
A61K 31/4545C07D 401/04C07D 401/14C07D 495/04A61P 11/00A61P 35/00A61P 25/28A61P 29/00A61K 31/454
67
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Claims
Abstract
The present disclosure provides compounds, for example, a compound of Formula (I), that modulate a protein function and/or restore protein homeostasis. The disclosure provides a method of modulating a protein-mediated disease, disorder, condition, or response. Compositions, including in combination with other therapeutic agents, are provided.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula (I):
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from the group consisting of
each X is independently CH 2 or C(═O);
Y is C(═O), C(═O)—(CR 6a R 6b ) n1 , C(═S), or C(═S)—(CR 6c R 6d ) n2 ;
R 2 is H, deuterium, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
ring A is C 6 -C 10 aryl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, each optionally substituted with one or more R A ;
R 3a , R 3b , R 3c , R 3d , R 3e , and R 3f are each independently H, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
each R 3g is independently deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
each R 4 is independently H, deuterium, halogen, or optionally substituted C 1 -C 6 alkyl;
each R 5 is independently H, deuterium, C 1 -C 6 alkyl,
each R 6a , R 6b , R 6e , R 6d , R 14 , and R 15 is independently H, substituted or unsubstituted amino, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or C 3 -C 8 carbocyclyl; or R 6a and R 6b together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; or R 6c and R 6d together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; wherein each C 3 -C 8 carbocyclyl is optionally substituted with one or more R B ;
each R 7a , R 7b , R 7c , R 7d , R 7e , R 8a , R 8b , R 8c , R 16 , and R 17 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 7 -C 14 aralkyl, or optionally substituted C 3 -C 8 carbocyclyl; or R 7a and R 8a together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7b and R 8b together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7c and R 8c together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; wherein each of C 6 -C 10 aryl, C 7 -C 14 aralkyl, C 3 -C 8 carbocyclyl, and 3 to 7 membered heterocyclyl is optionally substituted with one or more R B ;
each R 9 is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each of R 10a , R 10b , R 12 , and R 13 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R 11a , R 11b , R 11c , and R 11d is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R A is independently halogen, cyano, nitro, hydroxyl, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, wherein each of phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, and 3 to 10 membered heterocyclyl is optionally substituted with one or more R B ;
each R B is independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, halogen, or cyano; or two geminal R B form oxo;
m is an integer of 0, 1, 2, 3, 4, or 5;
n1 and n2 are each independently an integer of 0, 1, 2 or 3;
each p is independently an integer of 0, 1, or 2; and
each t is independently an integer of 0, 1, 2, 3, 4, or 5.
2 . The compound of claim 1 , being a compound of Formula (Ia):
or a pharmaceutically acceptable salt thereof.
3 . The compound of claim 1 , being a compound of Formula (Ib):
or a pharmaceutically acceptable salt thereof.
4 . The compound of claim 1 , being a compound of Formula (Ic):
or a pharmaceutically acceptable salt thereof.
5 . The compound of claim 1 , being a compound of Formula (Id):
or a pharmaceutically acceptable salt thereof.
6 . The compound of claim 1 , being a compound of Formula (Ie):
or a pharmaceutically acceptable salt thereof.
7 . The compound of claim 1 , being a compound of Formula (If):
or a pharmaceutically acceptable salt thereof.
8 . The compound of claim 1 , being a compound of Formula (Ig):
or a pharmaceutically acceptable salt thereof.
9 . The compound of claim 1 , being a compound of Formula (Ih):
or a pharmaceutically acceptable salt thereof.
10 . The compound of any one of claims 1 to 9 , wherein Y is (C═O)—(CH 2 ) n1 .
11 . The compound of any one of claims 1 to 10 , wherein Y is C(═O), C(═O)CH 2 , or C(═O)CH 2 CH 2 .
12 . A compound of Formula (III):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein:
R 1 is selected from the group consisting of
each X is independently CH 2 or C(═O);
R Z is —NR 7a R 8a or ring A; and ring A is C 6 -C 10 aryl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, each optionally substituted with one or more R A ;
R 2 is H, deuterium, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
R 3a , R 3b , R 3c , R 3d , R 3e , and R 3f are each independently H, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
each R 3g is independently deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
each R 4 is independently H, deuterium, halogen, or optionally substituted C 1 -C 6 alkyl;
each R 5 is independently H, deuterium, C 1 -C 6 alkyl,
each R 6a , R 6b , R 6c , R 6d , R 14 , and R 15 is independently H, substituted or unsubstituted amino, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or C 3 -C 8 carbocyclyl; or R 6a and R 6b together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; or R 6 and R 6d together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; wherein each C 3 -C 8 carbocyclyl is optionally substituted with one or more R B ;
each R 7a , R 7b , R 7c , R 7d , R 7e , R 8a , R 8b , R 8c , R 16 and R 17 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 7 -C 14 aralkyl, or optionally substituted C 3 -C 8 carbocyclyl; or R 7a and R 8a together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7b and R 8b together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7c and R 8c together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 16 and R 17 together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; wherein each of C 6 -C 10 aryl, C 7 -C 14 aralkyl, C 3 -C 8 carbocyclyl, and 3 to 7 membered heterocyclyl is optionally substituted with one or more R B ;
each R 9 is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each of R 10a , R 10b , R 12 , and R 13 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R 11a , R 11b , R 11c , and R 11d is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R A is independently halogen, cyano, nitro, hydroxyl, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, wherein each of phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, and 3 to 10 membered heterocyclyl is optionally substituted with one or more R B ;
each R B is independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, halogen, or cyano; or two geminal R B form oxo;
m is an integer of 0, 1, 2, 3, 4, or 5;
n1 is an integer of 0, 1, 2, or 3;
each p is independently an integer of 0, 1, or 2; and
each t is independently an integer of 0, 1, 2, 3, 4, 5, 6, 7, or 8.
13 . The compound of claim 12 , being a compound of Formula (IIIa):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
14 . The compound of claim 12 , being a compound of Formula (IIIb):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
15 . The compound of claim 12 , being a compound of Formula (IIIc):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
16 . The compound of claim 12 , being a compound of Formula (IIId):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
17 . The compound of claim 12 , being a compound of Formula (IIIe):
or a pharmaceutically acceptable salt thereof.
18 . The compound of claim 12 , being a compound of Formula (IIIf):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
19 . The compound of claim 12 , being a compound of Formula (IIIg):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
20 . The compound of claim 12 , being a compound of Formula (IIIh):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
21 . The compound of claim 12 , being a compound of Formula (IIIi):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
22 . A compound of Formula (IV):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein:
R 1 is selected from the group consisting of
each X is independently CH 2 or C(═O);
R Z is —NR 7a R 8a or ring A; and ring A is C 6 -C 10 aryl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, each optionally substituted with one or more R A ;
R 2 is H, deuterium, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
R 3a , R 3b , R 3c , R 3d , R 3e , and R 3f are each independently H, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
each R 3g is independently deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
each R 4 is independently H, deuterium, halogen, or optionally substituted C 1 -C 6 alkyl;
each R 5 is independently H, deuterium, C 1 -C 6 alkyl,
each R 6a , R 6b , R 6e , R 6d , R 14 , and R 15 is independently H, substituted or unsubstituted amino, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or C 3 -C 8 carbocyclyl; or R 6a and R 6b together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; or R 6c and R 6d together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; wherein each C 3 -C 8 carbocyclyl is optionally substituted with one or more R B ;
each R 7a , R 7b , R 7c , R 7d , R 7e , R 8a , R 8b , R 8c , R 16 , and R 17 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 7 -C 14 aralkyl, or optionally substituted C 3 -C 8 carbocyclyl; or R 7a and R 8a together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7b and R 8b together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7c and R 8c together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 16 and R 17 together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; wherein each of C 6 -C 10 aryl, C 7 -C 14 aralkyl, C 3 -C 8 carbocyclyl, and 3 to 7 membered heterocyclyl is optionally substituted with one or more R B ;
each R 9 is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each of R 10a , R 10b , R 12 , and R 13 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R 11a , R 11b , R 11c , and R 11d is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R A is independently halogen, cyano, nitro, hydroxyl, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, wherein each of phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, and 3 to 10 membered heterocyclyl is optionally substituted with one or more R B ;
each R B is independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, halogen, or cyano; or two geminal R B form oxo;
m is an integer of 0, 1, 2, 3, 4, or 5;
n1 is an integer of 0, 1, 2, or 3;
each p is independently an integer of 0, 1, or 2; and
each t is independently an integer of 0, 1, 2, 3, 4, 5, 6, 7, or 8.
23 . A compound of Formula (V):
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof; wherein:
R 1 is selected from the group consisting of
each X is independently CH 2 or C(═O);
R Z is —NR 7a R 8a or ring A; and ring A is C 6 -C 10 aryl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, each optionally substituted with one or more R A ;
R 2 is H, deuterium, optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
R 3a , R 3b , R 3c , R 3d , R 3e , and R 3f are each independently H, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , s (O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
each R 3g is independently deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted 5 to 10 membered heteroaryl;
each R 4 is independently H, deuterium, halogen, or optionally substituted C 1 -C 6 alkyl;
each R 5 is independently H, deuterium, C 1 -C 6 alkyl,
each R 6a , R 6b , R 6c , R 6d , R 14 , and R 15 is independently H, substituted or unsubstituted amino, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or C 3 -C 8 carbocyclyl; or R 6a and R 6b together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; or R 6c and R 6d together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; wherein each C 3 -C 8 carbocyclyl is optionally substituted with one or more R B ;
each R 7a , R 7b , R 7c , R 7d , R 7e , R 8a , R 8b , R 8c , R 16 , and R 17 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 7 -C 14 aralkyl, or optionally substituted C 3 -C 8 carbocyclyl; or R 7a and R 8a together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7b and R 8b together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7c and R 8c together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 16 and R 17 together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; wherein each of C 6 -C 10 aryl, C 7 -C 14 aralkyl, C 3 -C 8 carbocyclyl, and 3 to 7 membered heterocyclyl is optionally substituted with one or more R B ;
each R 9 is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each of R 10a , R 10b R 12 , and R 13 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R 11a , R 11b , R 11c , and R 11d is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R A is independently halogen, cyano, nitro, hydroxyl, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, wherein each of phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, and 3 to 10 membered heterocyclyl is optionally substituted with one or more R B ;
each R B is independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, halogen, or cyano; or two geminal R B form oxo;
m is an integer of 0, 1, 2, 3, 4, or 5;
n1 is an integer of 0, 1, 2, or 3;
each p is independently an integer of 0, 1, or 2; and
each t is independently an integer of 0, 1, 2, 3, 4, 5, 6, 7, or 8.
24 . The compound of any one of claims 12 to 23 , wherein R Z is ring A.
25 . The compound of any one of claims 1 to 24 , wherein X is CH 2 .
26 . The compound of any one of claims 1 to 24 , wherein X is C(═O).
27 . The compound of any one of claims 1 to 26 , wherein p is 1.
28 . The compound of any one of claims 1 to 26 , wherein p is 2.
29 . The compound of any one of claims 1 to 28 , wherein each of R 3a , R 3b , R 3c , R 3d , R 3e , and R 3f is H.
30 . The compound of any one of claims 1 , 10 to 12 , and 22 to 29 , wherein R 1 is
31 . The compound of any one of claims 1 , 10 to 12 , and 22 to 29 , wherein R 1 is
optionally substituted with one R 3g .
32 . The compound of any one of claims 1 , 10 to 12 , and 22 to 29 , wherein R 1 is
optionally substituted with one R 3g .
33 . The compound of any one of claims 1 , 8 to 12 , 19 to 29 , 31 , and 32 , wherein R 3g is halo, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl.
34 . The compound of claim 33 , wherein R 3g is fluoro or methyl.
35 . The compound of any one of claims 1 to 34 , wherein R 4 is H.
36 . The compound of any one of claims 1 to 35 , wherein R 5 is H.
37 . The compound of any one of claims 1 to 35 , wherein R 5 is
38 . The compound of claim 37 , wherein R 5 is valyloxymethyl.
39 . The compound of any one of claims 1 to 38 , wherein R 2 is H.
40 . The compound of any one of claims 1 to 39 , wherein ring A is C 6 -C 10 aryl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, each of which is optionally substituted with one, two, or three substituents R A .
41 . The compound of any one of claims 1 to 40 , wherein ring A is C 6 -C 10 aryl, optionally substituted with one, two, or three substituents R A .
42 . The compound of any one of claims 1 to 40 , wherein ring A is phenyl, optionally substituted with one, two, or three substituents R A .
43 . The compound of any one of claims 1 to 40 , wherein ring A is selected from the group consisting of pyridyl, thienyl, furyl, pyrimidinyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, and thiadiazolyl, each optionally substituted with one, two, or three R A .
44 . The compound of any one of claims 1 to 43 , wherein each substituent R A is independently halogen, cyano, hydroxyl, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, —(CH 2 ) t —NR 7a R 8a , —NR 7d C(O)R 11b , phenyl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, where each of phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, and 3 to 10 membered heterocyclyl is optionally substituted with one or more R B .
45 . The compound of any one of claims 1 to 44 , wherein ring A is phenyl, naphthyl, thienyl, pyridyl, piperidinyl, or cyclohexyl, each of which is optionally substituted with one, two, or three substituents R A , wherein each substituent R A is independently cyano, fluoro, chloro, bromo, methyl, trifluoromethyl-ethyl, trifluoromethyl, dimethylaminomethyl, morpholinylmethyl, propyl, butyl, hydroxyl-butyl, cyclopropyl, methylcyclopropyl, trifluoromethyl-cyclopropyl, phenyl, methyl-piperidinyl, hydroxyl, methoxy, dimethylamino, or acetamido.
46 . The compound of any one of claims 1 to 44 , wherein ring A is phenyl, cyanophenyl, fluorophenyl, chlorophenyl, bromophenyl, methylphenyl, (1-trifluoromethylethyl)-phenyl, trifluoromethylphenyl, dimethylaminomethylphenyl, morpholin-4-ylmethylphenyl, isopropylphenyl, sec-butylphenyl, tert-butylphenyl, (hydroxyl-tert-butyl)phenyl, cyclopropylphenyl, (1-methylcyclopropyl)phenyl, (1-trifluoromethylcyclopropyl)-phenyl, phenylphenyl, (1-methylpiperidin-4-yl)phenyl, hydroxylphenyl, methoxyphenyl, dimethylaminophenyl, acetamidophenyl, difluorophenyl, dichlorophenyl, chloro-methylphenyl, methyl-tert-butylphenyl, dimethylphenyl, trimethylphenyl, trimethoxyphenyl, dimethyl-tert-butylphenyl, dimethylamino-methylphenyl, naphthyl, thienyl, isopropylthienyl, pyridyl, tert-butylcyclohexyl, piperidinyl, or tert-butylpiperidinyl.
47 . The compound of any one of claims 1 to 44 , wherein ring A is phenyl, 4-cyanophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-(1-trifluoromethylethyl)-phenyl, 4-trifluoromethylphenyl, 4-dimethylaminomethylphenyl, 4-morpholin-4-ylmethylphenyl, 4-isopropylphenyl, 4-sec-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 4-(hydroxyl-tert-butyl)phenyl, 4-cyclopropylphenyl, 4-(1-methyl-cyclopropyl)phenyl, 4-(1-trifluoromethylcyclopropyl)phenyl, 4-phenylphenyl, 4-(1-methylpiperidin-4-yl)phenyl, 4-hydroxylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-dimethylaminophenyl, 4-acetamidophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3-chloro-4-methylphenyl, 3-methyl-4-tert-butylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,4,6-trimethoxyphenyl, 2,6-dimethyl-4-tert-butylphenyl, 3-dimethylamino-4-methylphenyl, 2-naphthyl, thien-2-yl, 5-isopropylthien-2-yl, 4-pyridyl, 4-tert-butylcyclohexyl, piperdin-4-yl, or 4-tert-butylpiperidin-1-yl.
48 . The compound of any one of claims 1 to 44 , wherein ring A is phenyl, 4-cyanophenyl, 2-fluorophenyl, 3-fluorophenyl, 3-chlorophenyl, 4-trifluoromethylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 4-(1-trifluoromethylcyclopropyl)phenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3-chloro-4-methylphenyl, 3-methyl-4-tert-butylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,4,6-trimethoxyphenyl, 2,6-dimethyl-4-tert-butylphenyl, 2-naphthyl, 5-isopropylthien-2-yl, 4-pyridyl, 4-tert-butylcyclohexyl, or 4-tert-butylpiperidin-1-yl.
49 . The compound of any one of claims 1 to 48 , wherein:
X is CH 2 or C(═O);
Y is C(═O), CH 2 C(O), CH 2 CH 2 C(O);
ring A is phenyl, 4-cyanophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-(1-trifluoromethylethyl)-phenyl, 4-trifluoromethylphenyl, 4-dimethylaminomethylphenyl, 4-morpholin-4-ylmethylphenyl, 4-isopropylphenyl, 4-sec-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 4-(hydroxyl-tert-butyl)phenyl, 4-cyclopropylphenyl, 4-(1-methylcyclopropyl)phenyl, 4-(1-trifluoromethylcyclopropyl)phenyl, 4-phenylphenyl, 4-(1-methylpiperidin-4-yl)phenyl, 4-hydroxylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-dimethylaminophenyl, 4-acetamidophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3-chloro-4-methylphenyl, 3-methyl-4-tert-butylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,4,6-trimethoxyphenyl, 2,6-dimethyl-4-tert-butylphenyl, 3-dimethylamino-4-methylphenyl, 2-naphthyl, thien-2-yl, 5-isopropylthien-2-yl, 4-pyridyl, 4-tert-butylcyclohexyl, piperdin-4-yl, or 4-tert-butylpiperidin-1-yl;
R 2 is H or methyl;
R 4 is H;
R 5 is H or D-valyloxymethyl;
R 3g is fluoro or methyl;
p is an integer of 1 or 2; and
m is an integer of 0, 1, or 2.
50 . The compound of claim 1 or 12 , wherein the compound is:
2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-1;
N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxo-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide I-3;
N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(5-isopropylthiophen-2-yl)-2-oxoacetamide I-4;
2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-6;
2-(4-dimethylaminophenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-7;
2-phenyl-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-8;
N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(thiophen-2-yl)-2-oxoacetamide I-9;
2-(4-methoxyphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-11;
2-(4-cyclopropylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-12;
2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4,6-dioxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-13;
2-(4-isopropylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-14;
2-(4-(sec-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-15;
2-(4-hydroxyphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-16;
2-(4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-17;
2-(4-chlorophenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-18;
2-(3-tert-butylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-19;
2-(4-acetamidophenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-20;
2-([1,1′-biphenyl]-4-yl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-21;
2-(4-fluorophenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-22;
2-(4-trifluoromethylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-23;
2-(3,4-dichlorophenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-24;
2-(4-((dimethylamino)methyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-25;
2-(4-(morpholinomethyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-26;
2-(3-methyl-4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-27;
N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-(1-methylpiperidin-4-yl)phenyl)-2-oxoacetamide I-31;
N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxo-2-(4-(1,1,1-trifluoropropan-2-yl)phenyl)acetamide I-36;
2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-40;
2-(4-(tert-butyl)phenyl)-N-(2-(5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)ethyl)-2-oxoacetamide I-41;
N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-(1-methylcyclopropyl)phenyl)-2-oxoacetamide I-42;
N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-(1-hydroxy-2-methylpropan-2-yl)phenyl)-2-oxoacetamide I-43;
2-(3-(dimethylamino)-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-oxoacetamide I-44;
N 1 -((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-N 2 ,N 2 -dimethyloxalamide I-70;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-2;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxo-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide I-5;
(S)-2-(4-(tert-butyl)phenyl)-N-((2-(2,7-dioxoazepan-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-10;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)methyl)-2-oxoacetamide I-32;
2-(3-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-33;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-N-methyl-2-oxoacetamide I-34;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-(5-isopropylthiophen-2-yl)-2-oxoacetamide I-37;
N-(2-(2-(2,6-Dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)ethyl)-2-oxo-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide I-52;
2-(3-chloro-4-methylphenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-53;
2-(3-methyl-4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-55;
N-((2-(2,6-dioxopiperidin-3-yl)-4-methyl-1-oxoisoindolin-5-yl)methyl)-2-oxo-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide I-60;
2-(4-(tert-butyl)piperidin-1-yl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-62;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxo-3-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)propanamide I-63;
2-(4-(tert-butyl)cyclohexyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-68;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxo-2-phenylacetamide I-83;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxo-2-(2,4,6-trimethoxyphenyl)acetamide I-84;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxo-2-(2,4,6-trimethylphenyl)acetamide I-85;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxo-2-(2-fluorophenyl)acetamide I-86;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxo-2-(4-trifluoromethylphenyl)acetamide I-87;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-(4-methoxyphenyl)-2-oxoacetamide I-89;
2-(4-cyanophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-90;
2-(3-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-91;
2-(3,4-difluorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-93;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-(3-methoxyphenyl)-2-oxoacetamide I-95;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-(naphthalen-2-yl)-2-oxoacetamide I-97;
2-(3,5-dimethylphenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-99;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-(3-fluorophenyl)-2-oxoacetamide I-100;
2-(3,4-dichlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-102;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxo-2-(pyridin-4-yl)acetamide I-103;
2-(4-(tert-butyl)-2,6-dimethylphenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2-oxoacetamide I-104;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-28;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-29;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxo-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide I-30;
2-(3-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-46;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-N-methyl-2-oxoacetamide I-47;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl)-2-oxoacetamide I-48;
(2R)-(3-(4-((2-(4-(tert-butyl)phenyl)-2-oxoacetamido)methyl)-1-oxoisoindolin-2-yl)-2,6-dioxopiperidin-1-yl)methyl 2-amino-3-methylbutanoate I-49;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-5-fluoro-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-50;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-5,6-difluoro-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-51;
2-(3-methyl-4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-54;
2-(4-(tert-butyl)phenyl)-N-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2-oxoacetamide I-56;
N-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)-2-oxo-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide I-57;
N-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)methyl)-2-oxo-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide I-58;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-(5-isopropylthiophen-2-yl)-2-oxoacetamide I-59;
2-(4-(tert-butyl)piperidin-1-yl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-61;
(2,6-dioxo-3-(1-oxo-4-((2-oxo-2-(4-(1-(trifluoromethyl)cyclopropyl)-phenyl)acetamido)methyl)isoindolin-2-yl)piperidin-1-yl)methyl D-valinate I-64;
N-(2-(2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)ethyl)-2-oxo-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide I-65;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxo-2-(4-(piperidin-4-yl)phenyl)acetamide I-66;
2-(4-(tert-butyl)cyclohexyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-67;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxo-2-(p-tolyl)acetamide 1-72;
2-(3,4-difluorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-73;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxo-2-phenylacetamide I-74;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxo-2-(4-(trifluoromethyl)phenyl)acetamide I-75;
2-(4-cyanophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-76;
2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-77;
2-(4-methoxyphenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-78;
2-(2,4,6-trimethoxyphenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-79;
2-(2,4,6-trimethylphenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-80;
2-(4-fluorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-81;
2-(2-fluorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-82;
2-(3-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-88;
2-(3-fluorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-92;
2-(3-methoxyphenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-94;
N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-(naphthalen-2-yl)-2-oxoacetamide I-96;
2-(3,5-dimethylphenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-98;
2-(3,4-dichlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-101;
2-(4-(tert-butyl)-2,6-dimethylphenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-105;
2-(4-bromophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-106;
2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2-oxoacetamide I-35;
2-(4-(tert-butyl)phenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-3-oxoisoindolin-4-yl)methyl)-2-oxoacetamide I-38;
2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-3-yl)methyl)-2-oxoacetamide I-39;
2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2-oxoacetamide I-45;
N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2-oxo-4-phenylbutanamide I-69;
N 1 -((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-N 2 ,N 2 -dimethyloxalamide I-71;
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
51 . The compound of claim 22 , wherein the compound is:
N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoro-2-(4-fluorophenyl)acetamide II-18; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoroacetamide II-28; (S)-2-(3-chloro-4-methylphenyl)-N-((5-(2,7-dioxoazepan-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoroacetamide II-29; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2,2-difluoroacetamide II-38; 2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoroacetamide II-129; N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoro-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide II-164; or N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoro-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide II-165;
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
52 . The compound of claim 23 , wherein the compound is (E)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-3-(4-(1-(trifluoromethyl)cyclopropyl)-phenyl)acrylamide II-149; or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
53 . A compound of Formula (IIa), (IIb), or (IIc):
or a pharmaceutically acceptable salt thereof, wherein:
each n is independently an integer of 0, 1, or 2;
one of R 1 and R 2 is selected from the group consisting of H, deuterium, hydroxyl, halogen, cyano, nitro, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, optionally substituted C 3 -C 8 carbocyclyl, optionally substituted C 6 -C 10 aryl, optionally substituted 3 to 10 membered heterocyclyl, and optionally substituted 5 to 10 membered heteroaryl; and the other of R 1 and R 2 is
each R 3 is independently H, deuterium, C 1 -C 6 alkyl,
each R 4 is independently H, deuterium, halogen, or optionally substituted C 1 -C 6 alkyl;
L is
Z 1 is C(═O), C(═NH), S(O) 2 or (CH 2 ) k ;
Z 2 is a bond, S, O, or NH;
Z 3 is C(═O) or S(O) 2 ;
ring A is C 6 -C 10 aryl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, each optionally substituted with one or more R A ;
each of R a1 , R a2 , and R a3 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 7 -C 14 aralkyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R b1 , R b2 , R c1 , and R c2 is independently H, hydroxyl, substituted or unsubstituted amino, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or C 3 -C 8 carbocyclyl; or R b1 and R c1 together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; or R b2 and R c2 together with the carbon atom to which they are attached form a C 3 -C 8 carbocyclyl; wherein each C 3 -C 8 carbocyclyl is optionally substituted with one or more R B ;
each R 5a , R 5b , R 10a , and R 10b is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each of R 6a and R 6b is independently H, halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, or C 3 -C 8 carbocyclyl;
each R 7a , R 7b , R 7c , R 7d , R 7e , R 8a , R 8b , R 8c , R 7 , and R 8 is independently H, optionally substituted C 1 -C 6 alkyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 7 -C 14 aralkyl, or optionally substituted C 3 -C 8 carbocyclyl; or R 7a and R 8a together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7b and R 8b together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; or R 7c and R 8c together with the nitrogen atom to which they are attached form optionally substituted 3 to 7 membered heterocyclyl; wherein each of C 6 -C 10 aryl, C 7 -C 14 aralkyl, C 3 -C 8 carbocyclyl, or 3 to 7 membered heterocyclyl is optionally substituted with one or more R B ;
each R 9 is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R 11a , R 11b , R 11c , and R 11d is independently optionally substituted C 1 -C 6 alkyl, optionally substituted C 2 -C 6 alkenyl, optionally substituted C 2 -C 6 alkynyl, optionally substituted C 6 -C 10 aryl, optionally substituted 5 to 10 membered heteroaryl, optionally substituted C 7 -C 14 aralkyl, optionally substituted 3 to 10 membered heterocyclyl, or optionally substituted C 3 -C 8 carbocyclyl;
each R A is independently halogen, cyano, nitro, hydroxyl, optionally substituted C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, —(CH 2 ) t —NR 7a R 8a , —O(CH 2 ) t —NR 7a R 8a , —C(O)NR 7b R 8b , —S(O) 2 NR 7c R 8c , —OR 9 , —SR 10a , —C(O)OR 10b , —C(O)R 11a , —NR 7d C(O)R 11b , —S(O) 2 R 11c , —NR 7e S(O) 2 R 11d , (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, or 3 to 10 membered heterocyclyl, wherein each of phenyl, 5 to 10 membered heteroaryl, C 3 -C 8 carbocyclyl, and 3 to 10 membered heterocyclyl is optionally substituted with one or more R B ;
each R B is independently C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkyl, C 1 -C 6 haloalkoxy, (C 1 -C 6 alkoxy)C 1 -C 6 alkyl, —O(C 1 -C 6 alkoxy)C 1 -C 6 alkyl, halogen, or cyano; or two geminal R B form oxo;
m1, m2, m3, and m4 are each independently an integer of 0, 1, 2, 3, 4 or 5;
k is an integer of 1, 2, 3, 4, 5 or 6; and
each t is independently an integer of 0, 1, 2, 3, 4, or 5;
provided that:
when, in Formula (IIa), one of R 1 or R 2 is H, n is 1 or 2, R 3 is H, R 4 is H, L is —CH 2 —NH—C(═O)—NH—CH 2 — or —CH 2 —NH—C(═O)—NH—*, then ring A is not 3-chloro-4-methylphenyl, wherein the symbol “*” indicates the attachment point to ring A;
when, in Formula (IIb), R 1 is H, n is 1 or 2, R 3 is H, R 4 is H, L is —NH—C(═O)—CH 2 —*, —CH 2 —NH—C(═O)—CH 2 —*, or —CH 2 —NH—C(═S)—NH—*, then ring A is not 3-chloro-4-methylphenyl, wherein the symbol “*” indicates the attachment point to ring A;
when, in Formula (IIb), R 1 is H, n is 1 or 2, R 3 is H, R 4 is H, L is —NH—C(═O)—NH—, —CH 2 —NH—C(═O)—NH—CH 2 —, or —CH 2 —NH—C(═O)—NH—*, then ring A is not any of 3-chloro-4-methylphenyl, 4-methyl-3-isopropylphenyl, 3-chloro-4-methyl-5-isopropylpheny, 3-chloro-4,6-dimethylphenyl, 4-methyl-3-trifluoromethylphenyl, 3-chloro-4-trifluoromethylphenyl, 6-chloro-5-methylpyrid-2-yl, and 2-methylpyrid-5-yl, wherein the symbol “*” indicates the attachment point to ring A; and
when, in Formula (IIc), R 1 is H, n is 1, R 3 is H, R 4 is H, L is —CH 2 —NH—C(═O)—NH—*, then ring A is not 3-chloro-4-methylphenyl, wherein the symbol “*” indicates the attachment point to ring A.
54 . The compound of claim 53 , having the structure of Formula (IIa), wherein R 2 is H.
55 . The compound of claim 53 , having the structure of Formula (IIb), wherein R 1 is H.
56 . The compound of any one of claims 53 to 55 , wherein n is an integer of 1.
57 . The compound of any one of claims 53 to 56 , wherein R 3 is H or C 1 -C 6 alkyl.
58 . The compound of claim 57 , wherein R 3 is H.
59 . The compound of any one of claims 53 to 57 , wherein R 3 is
and wherein R 5a and R Sb are each independently C 1 -C 6 alkyl.
60 . The compound of any one of claims 53 to 57 , wherein R 3 is
wherein R 7 and R 8 are each H, and R 6a and R 6b are each independently H or optionally substituted C 1 -C 6 alkyl.
61 . The compound of any one of claims 53 to 60 , wherein R 4 is H or C 1 -C 6 alkyl.
62 . The compound of claim 61 , wherein R 4 is H or C 1 -C 6 alkyl.
63 . The compound of any one of claims 53 to 62 , wherein L is
wherein each R a1 and R a2 is independently H or C 1 -C 6 alkyl, and wherein Z 2 is a bond or O.
64 . The compound of claim 63 , wherein L is
65 . The compound of claim 63 or 64 , wherein each m1 is independently 0, 1, or 2.
66 . The compound of any one of claims 63 to 65 , wherein each m2 is independently 0, 1, 2, or 3.
67 . The compound of any one of claims 53 to 66 , wherein L is
m1 is 0, and m2 is 1.
68 . The compound of any one of claims 53 to 66 , wherein L is
and wherein R a3 is H or C 1 -C 6 alkyl.
69 . The compound of claim 68 , wherein L is
70 . The compound of claim 68 or 69 , wherein each m3 is independently 0, 1 or 2.
71 . The compound of any one of claims 68 to 70 , wherein each m4 is independently 1, 2 or 3.
72 . The compound of any one of claims 68 to 71 , wherein both R b2 and R c2 are H.
73 . The compound of any one of claims 68 to 72 , wherein one of R b2 and R c2 is H, halogen, C 1 -C 6 alkyl, or C 1 -C 6 haloalkyl and the other one of R b2 and R c2 is halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 7 cycloalkyl, —NH 2 , —NH(C 1 -C 4 alkyl), —N(C 1 -C 4 alkyl) 2 , or hydroxyl.
74 . The compound of claim 73 , wherein R b2 is H and R c2 is hydroxyl, trifluoromethyl, methyl, ethyl, isopropyl, cyclopropyl, methoxy, —NH 2 , —NHCH 3 , —NHC 2 H 5 , —N(CH 3 ) 2 , or —N(C 2 H 5 ) 2 .
75 . The compound of claim 73 , wherein R b2 is fluoro or trifluoromethyl, and R c2 is fluoro or hydroxyl.
76 . The compound of any one of claims 68 to 75 , wherein R b2 and R c2 together with the carbon atom to which they are attached form a C 3 -C 7 cycloalkyl optionally substituted with one or more R B .
77 . The compound of any one of claims 53 to 76 , wherein ring A is phenyl, unsubstituted or substituted with one or more R A .
78 . The compound of any one of claims 53 to 76 , wherein ring A is selected from the group consisting of pyridyl, thienyl, furyl, pyrimidinyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, and thiadiazolyl, each independently unsubstituted or substituted with one or more R A .
79 . The compound of any one of claims 53 to 76 , wherein ring A is phenyl, naphthyl, thienyl, pyridyl, piperidinyl, or cyclohexyl, each of which is optionally substituted with one, two, or three substituents R A , wherein each substituent R A is independently cyano, fluoro, chloro, bromo, methyl, trifluoromethyl-ethyl, trifluoromethyl, dimethylaminomethyl, morpholinylmethyl, isopropyl, sec-butyl, tert-butyl, hydroxyl-tert-butyl, cyclopropyl, methylcyclopropyl, trifluoromethyl-cyclopropyl, phenyl, methyl-piperidinyl, hydroxyl, methoxy, dimethylamino, or acetamido.
80 . The compound of any one of claims 53 to 76 , wherein ring A is phenyl, cyanophenyl, fluorophenyl, chlorophenyl, bromophenyl, methylphenyl, (1-trifluoromethylethyl)phenyl, trifluoromethylphenyl, dimethylaminomethylphenyl, morpholin-4-ylmethylphenyl, isopropylphenyl, sec-butylphenyl, tert-butylphenyl, (hydroxyl-tert-butyl)phenyl, cyclopropylphenyl, (1-methylcyclopropyl)-phenyl, (1-trifluoromethylcyclopropyl)-phenyl, phenylphenyl, (1-methylpiperidin-4-yl)phenyl, hydroxylphenyl, methoxyphenyl, dimethylaminophenyl, acetamidophenyl, difluorophenyl, dichlorophenyl, chloro-methylphenyl, methyl-tert-butylphenyl, dimethylphenyl, trimethylphenyl, trimethoxyphenyl, dimethyl-tert-butylphenyl, dimethylamino-methylphenyl, naphthyl, thienyl, isopropylthienyl, pyridyl, tert-butylcyclohexyl, piperidinyl, or tert-butylpiperidinyl.
81 . The compound of any one of claims 53 to 76 , wherein ring A is phenyl, 4-cyanophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methylphenyl, 4-(1-trifluoromethylethyl)-phenyl, 4-trifluoromethylphenyl, 4-dimethylaminomethylphenyl, 4-morpholin-4-ylmethylphenyl, 4-isopropylphenyl, 4-sec-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 4-(hydroxyl-tert-butyl)phenyl, 4-cyclopropylphenyl, 4-(1-methyl-cyclopropyl)phenyl, 4-(1-trifluoromethylcyclopropyl)phenyl, 4-phenylphenyl, 4-(1-methylpiperidin-4-yl)phenyl, 4-hydroxylphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 4-dimethylaminophenyl, 4-acetamidophenyl, 3,4-difluorophenyl, 3,4-dichlorophenyl, 3-chloro-4-methylphenyl, 3-methyl-4-tert-butylphenyl, 3,5-dimethylphenyl, 2,4,6-trimethylphenyl, 2,4,6-trimethoxyphenyl, 2,6-dimethyl-4-tert-butylphenyl, 3-dimethylamino-4-methylphenyl, 2-naphthyl, thien-2-yl, 5-isopropylthien-2-yl, 4-pyridyl, 4-tert-butylcyclohexyl, piperdin-4-yl, or 4-tert-butylpiperidin-1-yl.
82 . The compound of claim 53 , wherein the compound is:
1-(3-(dimethylamino)-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-1; 1-(3-chloro-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-3-yl)methyl)urea II-2; (S)-1-(3-chloro-4-methylphenyl)-3-((5-(2,7-dioxoazepan-3-yl)-4-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-3; 1-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-3-(3-methoxy-4-methylphenyl)urea II-4; 1-(4-chloro-3-(trifluoromethoxy)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-5; 1-(3-chloro-4-methoxyphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-6; 1-(benzo[d][1,3]dioxol-5-yl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-7; 1-(3-chloro-5-(trifluoromethyl)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-8; 1-(3,5-bis(trifluoromethyl)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-9; 1-(3-chloro-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-10; 1-(3-(dimethylamino)-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-11; N-(5-(3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)ureido)-2-methylphenyl)acetamide II-12; 1-(3-chloro-4-(dimethylamino)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-13; N-(2-chloro-4-(3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)ureido)phenyl)acetamide II-14; 1-(3-chloro-4-methylbenzyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-3-yl)methyl)urea II-15; 5-(3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)ureido)-2-methylbenzamide II-16; (S)-1-(3-chloro-4-methylphenyl)-3-((5-(2,7-dioxoazepan-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-17; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoro-2-(4-fluorophenyl)acetamide II-18; (S)-1-(3-chloro-4-methylbenzyl)-3-((5-(2,7-dioxoazepan-3-yl)-4-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-19; 1-(3-chloro-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-1,3-dimethylurea II-20; 1-(3-chloro-4-methylbenzyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-21; 1-(3-chloro-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-1-methylurea II-22; 3-(1-(((3-((3-chloro-4-methylphenyl)amino)propyl)amino)methyl)-4-oxo-4H-thieno[3,4-c]pyrrol-5(6H)-yl)piperidine-2,6-dione II-23; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)acetamide II-24; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-fluorophenyl)acetamide II-25; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(3-methyl-4-morpholinophenyl)urea II-26; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(3-methyl-4-(pyrrolidin-1-yl)phenyl)urea II-27; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoroacetamide II-28; (S)-2-(3-chloro-4-methylphenyl)-N-((5-(2,7-dioxoazepan-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoroacetamide II-29; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)acetamide II-30; 1-(3-chloro-4-methylphenyl)-3-(2-(5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)ethyl)urea II-31; 1-(3-chloro-4-methylbenzyl)-3-(2-(5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)ethyl)urea II-32; 3-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)propenamide II-33; 3-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)propenamide II-34; 3-{2-[(3-chloro-4-methylphenylsulfonylamino)methyl]-6-oxo-3-thia-7-azabicyclo[3.3.0]octa-1,4-dien-7-yl}-2,6-piperidinedione II-35; 1-(2,6-dichlorobenzyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)ur II-36; 1-(2,6-dichlorobenzyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-37; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2,2-difluoroacetamide II-38; 1-(3-chloro-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)thiourea II-39; 1-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-3-(5-methyl-4-(trifluoromethyl)pyrimidin-2-yl)urea II-40; 4-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)butanamide II-41; 1-(2,6-dichlorophenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-42; 1-(2,6-dichlorophenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-43; 3-{3-[(3-chloro-4-methylphenylsulfonylamino)methyl]-8-oxo-2-thia-7-azabicyclo[3.3.0]octa-1(5),3-dien-7-yl}-2,6-piperidinedione II-44; 1-(3-(dimethylamino)-4-fluorophenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-45; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(3-hydroxy-4-methylphenyl)urea II-46; 1-(3-(diethylamino)-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-47; 1-(3-(dimethylamino)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-48; 1-(3-(dimethylamino)-5-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-49; 1-(3-(dimethylamino)-5-(trifluoromethyl)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-50; 1-(3-((dimethylamino)methyl)-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-51; 1-(4-(diethylamino)-3-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-52; 1-(3-((dimethylamino)methyl)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-53; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(3-isopropyl-4-methylphenyl)urea II-54; 1-(3-(dimethylamino)-4-(trifluoromethyl)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-55; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(3-(isopropyl(methyl)amino)phenyl)urea II-56; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-3-yl)methyl)acetamide II-57; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(3-methoxy-4-methylphenyl)urea II-58; 1-(4-(dimethylamino)-3-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-59; 1-(3-(dimethylamino)-5-isopropylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-60; 2-(4-(dimethylamino)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)acetamide II-61; 2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)acetamide II-62; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(3-isopropyl-4-methoxyphenyl)acetamide II-63; 3-(1-(((54(3-chloro-4-methylphenyl)amino)pentyl)amino)methyl)-4-oxo-4H-thieno[3,4-c]pyrrol-5(6H)-yl)piperidine-2,6-dione II-64; 3-(2-(((3-((3-chloro-4-methylphenyl)amino)propyl)amino)methyl)-6-oxo-4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)piperidine-2,6-dione II-65; 3-(2-(((3-((3-chloro-4-methylphenyl)amino)propyl)amino)methyl)-6-oxo-4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)piperidine-2,6-dione II-66; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)propenamide II-67; 2-(3-(dimethylamino)-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)acetamide II-68; 1-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)methanesulfonamide II-69; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(3-isopropylphenyl)urea II-70; 1-(3-(diethylamino)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-71; 1-(3-chloro-4-methylphenyl)-3-((5-(2,5-dioxopyrrolidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-72; 1-(3-chloro-4-methylphenyl)-3-((5-(3-methyl-2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-73; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-isopropylphenyl)acetamide II-74; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-methylcyclohexyl)acetamide II-75; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(3-(piperidin-1-yl)phenyl)acetamide II-76; 2-(3-(2-(dimethylamino)ethoxy)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)acetamide II-77; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-morpholinoacetamide II-78; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)acetamide II-79; 2-(4-(2-(dimethylamino)ethoxy)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)acetamide II-80; (3-(24(3-(3-(dimethylamino)-4-methylphenyl)ureido)methyl)-6-oxo-4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)-2,6-dioxopiperidin-1-yl)methyl D-valinate II-81; (3-(24(3-(3-chloro-4-methylphenyl)ureido)methyl)-6-oxo-4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)-2,6-dioxopiperidin-1-yl)methyl D-valinate II-82; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-morpholinophenyl)acetamide II-83; 4-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)butanamide II-84; 4-(4-(dimethylamino)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)butanamide II-85; 4-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-methylbutanamide II-86; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)butanamide II-87; 2-amino-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(p-tolyl)acetamide II-88; 2-amino-2-(3-chlorophenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)acetamide II-89; (S)-1-(3-chloro-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-90; (R)-1-(3-chloro-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-91; 2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)propenamide II-92; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-(pyrrolidin-1-yl)phenyl)acetamide II-93; 2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-3-methylbutanamide II-94; 2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-3-methylbutanamide II-95; 1-(3-(dimethylamino)-4-ethylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-96; 1-(3-(diethylamino)-4-fluorophenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-97; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(4-methyl-3-(pyrrolidin-1-yl)phenyl)urea II-98; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(3-(pyrrolidin-1-yl)phenyl)urea II-99; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(3-(ethyl(methyl)amino)-4-methylphenyl)urea II-100; 4-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-methylbutanamide II-101; (2S)-2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)propenamide II-102; (2R)-2-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)propenamide II-103; (S)-4-(3-chloro-4-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-dimethylbutanamide II-104; di-tert-butyl ((3-(2-((3-(3-(dimethylamino)-4-methylphenyl)ureido)-methyl)-6-oxo-4,6-dihydro-5H-thieno[2,3-c]pyrrol-5-yl)-2,6-dioxopiperidin-1-yl)methyl) phosphate II-105; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-isopropylphenyl)-3-methylbutanamide II-106; N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2-(perfluorophenyl)acetamide II-107; 2-(dimethylamino)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(2-fluorophenyl)acetamide II-108; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-4-phenylbutanamide II-109; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-phenylthiourea II-110; 1-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-3-(4-(trifluoromethoxy)phenyl)thiou II-111; 2-amino-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-propoxyphenyl)acetamide II-112; 2-amino-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-(4-hydroxyphenyl)acetamide II-113; 1-(3-(dimethylamino)-4-methylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4,6-dioxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-114; 4-(4-(dimethylamino)-3-methylphenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)butanamide II-115; N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2-(3-fluoro-2-methoxyphenyl)acetamide II-116; 4-bromo-2,5-dichloro-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)thiophene-3-sulfonamide II-117; methyl 5-chloro-3-(N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)sulfamoyl)thiophene-2-carboxylate II-118; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide II-119; N-(5-(N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)sulfamoyl)-4-methylthiazol-2-yl)acetamide II-120; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,3,4,5,6-pentafluorobenzenesulfonamide II-121; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-1-methyl-1H-imidazole-4-sulfonamide II-122; 1-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-3-(2,3,5,6-tetrachlorophenyl)thiourea II-123; 4-(tert-butyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)benzenesulfonamide II-124; methyl 3-(3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)ureido)thiophene-2-carboxylate II-125; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)thiazole-2-carboxamide II-126; 1-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)cyclopropane-1-carboxamide II-127; 1-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)methanesulfonamide II-128; 2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoroacetamide II-129; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)furan-3-sulfonamide II-130; 4-(tert-butyl)-N-(2-(5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)ethyl)benzenesulfonamide II-131; 2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2-hydroxyacetamide II-132; 2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-3,3,3-trifluoro-2-hydroxypropanamide II-133; 3-bromo-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)furan-2-carboxamide II-134; 4-bromo-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2-(trifluoromethoxy)benzenesulfonamide II-135; 2-chloro-N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)thiazole-5-carboxamide II-136; methyl 2-(3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)ureido)thiophene-3-carboxylate II-137; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(6-morpholinopyridin-3-yl)urea II-138; 1-(1,3-dimethyl-1H-pyrazol-5-yl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-139; N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3,5-dimethylisoxazole-4-carboxamide II-140; N-(5-(N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)sulfamoyl)-4-methylthiazol-2-yl)acetamide II-141; N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2,5-dimethylfuran-3-sulfonamide II-142; 5-(N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)sulfamoyl)-2-methoxy-N,N-dimethylbenzamide II-143; N-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-2-(propylthio)nicotinamide II-144; 1-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-3-(3-phenoxypropyl)urea II-145; N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-4-(4-morpholinophenyl)butanamide II-146; 2-(4-(tert-butyl)phenyl)-N-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-3,3,3-trifluoropropanamide II-147; 1-(4-(tert-butyl)phenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)urea II-148; 1-(2,3-dimethylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-150; 1-(2,4-dimethylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-151; 1-(2,5-dimethylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-152; 1-([1,1′-biphenyl]-4-yl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-153; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(4-methoxyphenyl)urea II-154; 1-(4-cyanophenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-155; 1-(2,6-dimethylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-155; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-phenethylthiourea II-157; 1-(2-trifluoromethylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-158; 1-(3-cyanophenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-159; 1-(4-chloro-2-trifluoromethylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-160; 1-(2,4,6-trimethylphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-161; 1-(3,5-dimethoxyphenyl)-3-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)urea II-162; 1-((5-(2,6-dioxopiperidin-3-yl)-6-oxo-5,6-dihydro-4H-thieno[2,3-c]pyrrol-2-yl)methyl)-3-(naphthalen-1-yl)urea II-163; or N-((5-(2,6-Dioxopiperidin-3-yl)-4-oxo-5,6-dihydro-4H-thieno[3,4-c]pyrrol-1-yl)methyl)-2,2-difluoro-2-(4-(1-(trifluoromethyl)cyclopropyl)phenyl)acetamide II-165;
or an enantiomer, a mixture of enantiomers, a diastereomer, a mixture of two or more diastereomers, a tautomer, a mixture of two or more tautomers, or an isotopic variant thereof; or a pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof.
83 . A pharmaceutical composition comprising a compound of any one of claims 1 to 82 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
84 . A method of treating, ameliorating, or preventing a disease, disorder, or condition associated with a protein in a subject, comprising administering a therapeutically effective amount of a compound of any one of claims 1 to 82 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 83 ; wherein the protein is a cytokine, aiolos, ikaros, helios, CK1α, or GSPT1.
85 . The method of claim 84 , wherein the protein is a cytokine.
86 . The method of claim 84 or 85 , wherein the cytokine is IL-1β, IL-6, TNFα, and IL-2.
87 . The method of any one of claims 84 to 86 , wherein the disease, disorder, or condition is inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, or cancer.
88 . The method of claim 87 , wherein the disease, disorder, or condition is cancer.
89 . The method of claim 88 , wherein the cancer is breast cancer, melanoma, renal cancer, prostate cancer, colon cancer, lung cancer, bladder cancer, brain cancer, cervical cancer, head and neck cancer, esophageal and gastric cancers, osteosarcoma, multiple myeloma, leukemia, lymphoma, neuroendocrine cancer, hepatocellular carcinoma, renal cell cancer, pancreatic cancer, thyroid cancer, glioblastoma, ovarian, endometrial cancer, or astrogliosis.
90 . The method of any one of claims 84 to 89 , wherein the subject is a human.
91 . A method of modulating a protein activity in a cell, comprising contacting the cell with an effective amount of a compound of any one of claims 1 to 82 , or a pharmaceutically acceptable salt thereof, wherein the protein is a cytokine, aiolos, ikaros, helios, CK1α, or GSPT1.
92 . The method of claim 91 , wherein the method is to inhibit the protein activity.
93 . The method of claim 91 or 92 , wherein the cytokine is IL-1β, IL-6, TNFα, or IL-2.Join the waitlist — get patent alerts
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