Substituted 3-amino-4-methylbenzenesulfonamides as small molecule inhibitors of ubiquitin-specific protease 28
AssigneeDana-Farber Cancer Institute, Inc.
InventorsSara Buhrlage, Anthony Varca, Bin Hu
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Abstract
The present disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof and pharmaceutical composition comprising the compound of formula (I). The present composition also relates to methods treating a disease or disorder associated with ubiquitin-specific protease 28 (USP28), methods of treating cancer, and methods of inhibiting USP28.
Claims41
A compound of formula (I)
- or a pharmaceutically acceptable salt thereof, wherein, independently for each occurrence,
- X1 is —C(═O)NR8(C1-3 alkyl) or —S(O)2R1;
- R1 is C1-2 alkyl or —NR4R5;
- R4 is H or C1-3 alkyl;
- R5 is C1-3 alkyl or C6-10 aryl, or
- R4 and R5, together with the nitrogen atom to which they are attached, optionally form a C5-8 heterocyclyl;
- R2 is H, C1-3 alkyl, —OR6, or Hal;
- R6 is H, C1-3 alkyl, or —C(Hal)3;
- Z1 is —C(═O)— or —NR8—;
- R8 is H or C1-3 alkyl;
- Z2 is —C(═O)— or —NR8—, or
- R2, Z2, and Z1, taken together with the atoms to which they are attached, form a C5-6 heteroaryl,
- Z3 is absent or C1-3 alkylene;
- and
- R3 is C6-10 aryl, C5-6 heteroaryl, or C5-8 heterocyclyl;
- and wherein
- each C1-3 alkyl, C6-10 aryl, C5-6 heteroaryl, and C5-8 heterocyclyl is independently optionally substituted with one or more groups selected from C1-3 alkyl, C6-10 aryl, C5-8 heterocyclyl, Hal,
- —C(Hal)3, —OH, —NO2, —NHC(═O)(C1-3 alkyl), and —NH(C1-3 alkyl), or a combination thereof;
- provided the compound is not
The compound of any one of the preceding claims, wherein Z1 is —NR8—;
The compound of any one of the preceding claims, wherein R2, Z2, and Z1, taken together with the atoms to which they are attached, form a C5-6 heteroaryl.
The compound of any preceding claim, wherein R4 is H.
The compound of any preceding claim, wherein R5 is C1-3 alkyl.
The compound of any one of the preceding claims, wherein Z3 is C1-2 alkylene.
The compound of any one of the preceding claims, wherein Z3 is C1 alkylene.
The compound of any one of the preceding claims, wherein R3 is C6-10 aryl.
The compound of any one of the preceding claims, wherein R3 is phenyl.
The compound of any one of the preceding claims, wherein R3 is substituted with one or more groups selected from C1-3 alkyl, C6-10 aryl, C5-8 heterocyclyl, —OH, Hal, —C(Hal)3, —NO2,
- —NHC(═O)(C1-3 alkyl), and —NH(C1-3 alkyl), or a combination thereof.
The compound of any one of the preceding claims, wherein R3 is
A pharmaceutical composition comprising a compound of any one of the preceding claims and a pharmaceutically acceptable carrier.
The method of claim 38, wherein the disease or disorder associated with USP28 is cancer.
Dependencies are inferred from the claim text.