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US 2010/0075949 A1Published application
Novel pyrrolidin-2-ones
AssigneePriaxon AG
InventorsChristoph BURDACK, Cedric KALINSKI, Vladimir KHAZAK, Gunther ROSS, Lutz WEBER
Life of this patent
Estimating the term…
Abstract
The present invention provides compounds of formula (I) or (Ia) which are ligands binding to the HDM2 protein, inducing apoptosis and inhibiting proliferation, and having therapeutic utility in cancer therapy and prevention. Compounds of formula (I) or (Ia) can be used as therapeutics for treating stroke, myocardial infarction, ischemia, multi-organ failure, spinal cord injury, Alzheimer's Disease, injury from ischemic events and heart valvular degenerative disease. Moreover, compounds of formula (I) or (Ia) can be used to decrease the side effects from cytotoxic cancer agents, radiation and to treat viral infections.
Claims16
A compound of formula (I):
- wherein
- V is C═O, C═S or CH2;
- X is sulphur, oxygen or a group of formula CH2, CR4bR4c, NH, NR4b, SO, SO2 or a bond;
- Y is a group of formula CONR6, CH2NR6, CO, COO, CH2O, SO2NR6, NR6CO, NR6SO2, NR5aCONR6, NR6COO, OCONR6, CONR5aNR6, CONR5aOR6, CH2CO CH2CONR6, CH2COO, COCR5aR6 or a bond;
- n is 1, 2, 3 or 0;
- R1 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R2 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R3 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R4 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R4b is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R4c is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R5 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R5a is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R6 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- the residues R7 are independently from each other a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- the residues R8 are independently from each other a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- or two of the radicals R1, R2, R3, R4, R4b, R4c, R5, R5a, R6, R7 and R8 together are part of an optionally substituted cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heteroaryl, aralkyl or heteroarylalkyl ring system;
- or a pharmaceutically acceptable salt, ester, solvate or hydrate or a pharmaceutically acceptable formulation thereof.
15 more elements
A compound of formula (Ia)
- wherein
- R1 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R2 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R3 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R4 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R5 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- R6 is a hydrogen atom or an alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, cycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, heterocycloalkyl, aralkyl or heteroaralkyl radical;
- or the radicals R5 and R6 together are part of an optionally substituted heterocycloalkyl, heteroalkylcycloalkyl, heteroaryl or heteroarylalkyl ring system, and/or R2 and R3 together are part of an optionally substituted cycloalkyl, alkylcycloalkyl, heterocycloalkyl, heteroalkylcycloalkyl, aralkyl or heteroaralkyl ring system;
- or a pharmaceutically acceptable salt, ester, solvate or hydrate or a pharmaceutically acceptable formulation thereof.
6 more elements
Dependencies are inferred from the claim text.