Therapeutic compounds
AssigneeCelgene Quanticel Research, Inc.
InventorsLynnie Trzoss, Juan Manuel Betancort, Toufike Kanouni, Michael Brennan Wallace, Amogh Boloor
Life of this patent
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Abstract
The present embodiments relate to substituted heterocyclic derivative therapeutic compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of diseases mediated by aberrant cell signalling, such as inflammatory disorders, cancer and neoplastic disease. Particular compounds described herein exhibit selective inhibitory activity against CBP compared with BRD4.
Claims44
A compound having the structure of Formula I:
- wherein a compound of Formula I includes a pharmaceutically acceptable salt thereof, and
- wherein
- X6 is CR7, wherein R7 is hydrogen, or alkyl;
- R2 is CH3;
- R5 is halogen, —N(R22)2, —NH(R22), —OW, —SW, or optionally substituted alkyl, aryl, aralkyl, cycloalkyl, or cycloalkylalkyl, wherein
- W is optionally substituted alkyl, aryl, aralkyl, cycloalkyl, heterocyclyl, or heteroarylalkyl;
- R6 is methyl;
- RA is
- wherein X is a bond, CH2, CHR, or CRR′;
- wherein
- R and R′ are independently halogen, halide, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, —SO2R21, or —N(R22)SO2R21;
- wherein
- each R21 is independently selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;
- each R22 is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;
- and
- R1 is hydrogen or optionally substituted alkyl, aryl, aralkyl, alkoxy, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl.
A compound having the structure of Formula I:
- wherein a compound of Formula I includes a pharmaceutically acceptable salt thereof, and
- wherein
- X6 is CR7, wherein R7 is hydrogen, or alkyl;
- R2 is CH3;
- R5 is optionally substituted alkyl halogen
- R6 is hydrogen, halogen, alkyl, or —OR22;
- RA is
- wherein X is a bond, CH2, CHR, or CRR′;
- wherein
- R and R′ are independently halogen, halide, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, heteroarylalkyl, —SO2R21, or —N(R22)SO2R21;
- wherein
- each R21 is independently selected from alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;
- each R22 is independently selected from hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl;
- and
- R1 is hydrogen or optionally substituted alkyl, aryl, aralkyl, alkoxy, cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heteroaryl, or heteroarylalkyl.
Dependencies are inferred from the claim text.