Isoquinolinone derivatives
AssigneesMaybridge Limited, Kudos Pharmaceuticals Limited
InventorsNiall Morrison Barr Martin, Graeme Cameron Murray Smith, Charles Richard White, Roger Frank Newton, Diana Gillian Douglas, Penny Jane Eversley, Alan John Whittle
Life of this patent
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Abstract
Derivatives of isoquinolinone and dihydrolisoquinolinone, and related compounds, and their use as pharmaceuticals in the treatment of a disease by inhibition of the enzyme poly(ADP-ribose)polymerase (“PARP”) are disclosed.
Claims10
A method of treatment of a disease of the human or animal body mediated by PARP comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula:
- or an isomer, salt, solvate, chemically protected form, or prodrug thereof, wherein:
- A and B together represent a fused benzene ring which is optionally substituted with one or more substituents selected from the group consisting of halo, nitro, hydroxy, ether, thiol, thioether, amino, C1-7 alkyl, C3-20 heterocyclyl, and C5-20 aryl;
- wherein one or more of the substituents may together form a ring;
- the dotted line between the 3 and 4 positions indicates the optional presence of a double bond;
- one of RC1 and RC2 is represented by -L-RL, and the other of RC1 and —RC2 is H, where L is of formula:
- —(CH2)n1—
- wherein n1 is 1 or 2, and wherein RL is selected from optionally substituted C5-20 aryl;
- and
- RN is hydrogen.
A method of potentiating tumour cells for treatment with ionising radiation or chemotherapeutic agents comprising administering to said cells a compound of formula:
- or an isomer, salt, solvate, chemically protected form, or prodrug thereof, wherein:
- A and B together represent a fused benzene ring which is optionally substituted with one or more substituents selected from the group consisting of halo, nitro, hydroxy, ether, thiol, thioether, amino, C1-7 alkyl, C3-20 heterocyclyl, and C5-20 aryl;
- wherein one or more of the substituents may together form a ring;
- the dotted line between the 3 and 4 positions indicates the optional presence of a double bond;
- one of RC1 and RC2 is represented by -L-RL, and the other of RC1 and —RC2 is H, where L is of formula:
- —(CH2)n1—
- wherein n1 is 1 or 2, and wherein RL is selected from optionally substituted C5-20 aryl;
- and
- RN is hydrogen.
A compound of the formula:
- or an isomer, salt, solvate, chemically protected form, or prodrug thereof, wherein:
- A and B together represent an optionally substituted, fused aromatic ring;
- the dotted line between the 3 and 4 positions indicates the optional presence of a double bond;
- one of RC1 and RC2 is —CH2—RL, and the other of RC1 and RC2 is H;
- RL is optionally substituted fluoro-phenyl;
- and
- RN is hydrogen.
A pharmaceutical composition comprising compound of the formula:
- or an isomer, salt, solvate, chemically protected form, and or prodrug thereof, wherein:
- A and B together represent an optionally substituted, fused aromatic ring;
- the dotted line between the 3 and 4 positions indicates the optional presence of a double bond;
- one of RC1 and RC2 is —CH2—RL, and the other of RC1 and RC2 is H;
- RL is optionally substituted phenyl;
- and
- RN is hydrogen;
- and a pharmaceutically acceptable carrier or diluent.
Dependencies are inferred from the claim text.