Novel compounds
AssigneeMission Therapeutics Limited
InventorsAlison Jones, Mark Ian Kemp, Martin Lee Stockley, Karl Richard Gibson, Gavin Alistair Whitlock, Andrew Madin
Life of this patent
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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 L1 (UCHL1). The invention further relates to the use of DUB inhibitors in the treatment of cancer and other indications. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1 to R8 are as defined herein.
Claims12
1-17. (canceled)
A compound of formula (I)
- a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer, wherein:
- R1 represents a 6-membered monocyclic heteroaryl ring comprising 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulphur, and which is substituted with 1 to 4 Q1-(R9)n;
- R2, R3, R4, R5, R6 and R are each independently selected from hydrogen, C1-C3 alkyl and C1-C3 alkoxy, wherein said alkyl and alkoxy groups are optionally substituted with halo, C1-C3 alkyl or C1-C3 alkoxy;
- R7 is selected from hydrogen, methyl, CF3, phenyl, pyridyl and pyrimidyl;
- n is 0 or 1;
- Q1 represents a hydrogen atom, a halogen atom, cyano, a covalent bond, —NR10—, —CONR10—, —NR10CO—, an oxygen atom, oxo, nitro, —S(O)m—, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 hydroxyalkyl, —CO—, —SO2R11, —NR11R12, —NR11COR12, —NR10CONR11R12, —CONR11R12, —CO2R11, —NR11CO2R12, —SO2NR11R12, —C(O)R11, —NR11SO2R12, NR11SO2NR13R14, and SO2NR11, C1-C6 alkylene, —C2-C6 alkenylene, —C1-C6 alkyl, or C1-C2 haloalkyl group;
- m is 0, 1 or 2;
- R9 represents a 3 to 10-membered heterocyclyl, heteroaryl, aryl or cycloalkyl ring;
- and
- R10, R11 and R12 each independently represent a hydrogen atom, a C1-C6 alkyl, or a C1-C6 alkylene group;
- wherein R9 may be optionally substituted with one or more substituents selected from halogen, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl, oxo, cyano, nitro, heterocyclyl, cycloalkyl, heteroaryl, aryl, -Q2-NR13CONR14R15, -Q2-NR13R14, -Q2-NR13COR14, -Q2-COR13, -Q2-SO2R13, -Q2-CONR13, Q2-CONR13R14, -Q2-CO2R13, -Q2-SO2NR13R14, -Q2-NR13SO2R14, and -Q2-NR13SO2NR14R15;
- wherein said alkyl, alkoxy and heteroaryl groups may be optionally substituted with halo, deutero, C1-3 alkyl, hydroxy, C1-3 alkoxy, cyano, amino, nitro, oxo, aryl, heteroaryl, heterocyclyl, C3-C6 cycloalkyl, C1-3 alkylamino, C2-6 alkenylamino, di-C1-3 alkylamino, C1-3 acylamino, di-C1-3 acylamino, carboxy, C1-3 alkoxycarbonyl, carbamoyl, mono-C1-3 carbamoyl, di-C1-3 carbamoyl or any of the above in which a hydrocarbyl moiety is itself substituted by halo;
- or R9 may be substituted with a 3 to 10-membered heterocyclyl, heteroaryl, aryl or cycloalkyl ring, either directly attached or via linking group selected from oxygen, a carbonyl, an optionally substituted C1-C6 alkylene or an optionally substituted C1-C6 alkyleneoxy chain;
- Q2 represents a covalent bond or a C1-C6 alkylene or C2-C6 alkenylene group;
- and
- R13, R14 and R15 each independently represent hydrogen, C1-C6 alkyl, heterocyclyl, heteroaryl, aryl, or cycloalkyl;
- wherein said alkyl group may be optionally substituted with halo, deutero, C1-3 alkyl, hydroxy, C1-3 alkoxy, cyano, amino, nitro, oxo, aryl, heteroaryl, heterocyclyl, C3-C6 cycloalkyl, C1-3 alkylamino, C2-6 alkenylamino, di-C1-3 alkylamino, C1-3 acylamino, di-C1-3 acylamino, carboxy, C1-3 alkoxycarbonyl, carbamoyl, mono-C1-3 carbamoyl, di-C1-3 carbamoyl or any of the above in which a hydrocarbyl moiety is itself substituted by halo.
Dependencies are inferred from the claim text.