Compounds
AssigneeMission Therapeutics Limited
InventorsMark Ian Kemp, Martin Lee Stockley, Andrew Madin
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or Ubiquitin Specific Peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the Invention include compounds having the formula (I): (I) or a pharmaceutically acceptable salt thereof, wherein R1a, R1b, R1c, R1d, R1e, R1f, R1g, R2, X, L and A are as defined herein.
Claims14
A compound of formula (I):
- a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer, wherein:
- R1b, R1c, R1d and R1e are each independently selected from hydrogen and C1-C6 alkyl;
- R1a and R1g are each independently selected from hydrogen, fluorine, cyano, hydroxyl, amino, C1-C6 alkyl and C1-C6 alkoxy;
- R1f is selected from hydrogen, fluorine, cyano, hydroxyl, amino, C1-C6 alkyl and C1-C6 alkoxy;
- R2 is selected from hydrogen and C1-C6 alkyl;
- X is C(R3)(R4), wherein R3 and R4 are each independently selected from hydrogen, cyano and C1-C6 alkyl;
- L is a covalent bond;
- A is selected from a 5 to 6-membered monocyclic heteroaryl ring and a 9 to 10-membered bicyclic heteroaryl ring;
- wherein ring A is substituted with one to four -Q1-(R6)n, wherein each occurrence of -Q1-(R6)n is the same or different;
- n is 0 or 1;
- when n is 0, Q1 is selected from halogen, cyano, oxo, nitro, —OR7, —SR7, —NR7R8, —CONR7R8, —NR7COR8, —NR7CONR8R9, —COR7, —C(O)OR7, —NR7C(O)OR8, C1-C6 alkyl and C1-C6 alkoxy;
- when n is 1, Q1 is selected from a covalent bond, an oxygen atom and C1-C6 alkylene;
- R7 and R8 are each independently selected from hydrogen and C1-C6 alkyl;
- R6 is selected from 5 to 6-membered monocyclic heteroaryl, 9 to 10-membered bicyclic heteroaryl, cyclopropyl, phenyl and naphthyl;
- wherein R6 is optionally substituted with one to four substituents, each independently selected from halogen, cyano, oxo, nitro, —OR10, —SR10, —NR10R11, C1-C6 alkyl and C1-C6 alkoxy;
- R10 and R11 are each independently selected from hydrogen and C1-C6 alkyl;
- and
- wherein said C1-C6 alkyl and C1-C6 alkoxy groups are optionally substituted with one to four substituents, each independently selected from halogen, hydroxyl, thiol, cyano, amino, nitro and SF5.
Dependencies are inferred from the claim text.