# US 7,407,957 B2 · Phthalazinone derivatives

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- Number: US 7,407,957 B2
- Document ID: US7407957B2
- Status: Granted
- Kind: B2
- Application number: 11/213,504
- Filed: 2005-08-26
- Published: 2006-03-23
- Granted: 2008-08-05
- Earliest claimed: 2004-08-26
- Assignees: Maybridge Limited; Kudos Pharmaceuticals Limited
- Inventors: Muhammad Hashim Javaid; Graeme Cameron Murray Smith; Naill Morrison Barr Martin; Sylvie Gomez; Vincent Junior Ming-lai Loh; Xiao-Ling Fan Cockcroft; Stefano Forte; Keith Allan Menear; Ian Timothy William Matthews; Frank Kerrigan
- Web page: https://patentgrep.com/patent/US7407957B2

## CPC

- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/20: for DNA viruses
- A61P 35/00: Antineoplastic agents
- C07D 401/14: containing three or more hetero rings
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 409/14: containing three or more hetero rings
- C07D 417/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A compound of formula (I): for use in treating cancer or other diseases ameliorated by the inhibition of PARP, wherein: A and B together represent an optionally substituted, fused aromatic ring; X can be NRX or CRXRY; if X=NRX then n is 1 or 2 and if X=CRXRY then n is 1; RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups; RY is selected from H, hydroxy, amino; or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group; RC1 and RC2 are independently selected from the group consisting of hydrogen and C1-4 alkyl, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; R1 is selected from H and halo; and Het is selected from: where Y1 is selected from CH and N, Y2 is selected from CH and N, Y3 is selected from CH, CF and N, where only one or two of Y1, Y2 and Y3 can be N; and where Q is O or S.

## Claims

### Claim 1

A compound of formula (I):
and isomers, salts and solvates thereof, wherein:
A and B together represent an optionally substituted, fused aromatic ring;
X can be NRX or CRXRY;
if X=NRX then n is 1 or 2 and if X=CRXRY then n is 1;
RX is selected from the group consisting of H, optionally substituted C1-20 alkyl, C5-20 aryl, C3-20 heterocyclyl, amido, thioamido, ester, acyl, and sulfonyl groups;
RX is selected from H, hydroxy, amino;
or RX and RY may together form a spiro-C3-7 cycloalkyl or heterocyclyl group;
RC1 and RC2 are independently selected from the group consisting of hydrogen and C1-4 alkyl, or when X is CRXRY, RC1, RC2, RX and RY, together with the carbon atoms to which they are attached, may form an optionally substituted fused aromatic ring; and
Het is selected from:
where Y1 is selected from CH and N, Y2 is selected from CH and N, Y3 is selected from CH, CF and N, where one or two of Y1, Y2 and Y3 are N; and
where Q is O or S.

### Claim 2 (depends on 1)

A compound according to claim 1, wherein the fused aromatic ring(s) represented by -A-B- consist of solely carbon ring atoms.

### Claim 3 (depends on 2)

A compound according to claim 2, wherein the fused aromatic ring represented by -A-B- is benzene.

### Claim 4 (depends on 1)

A compound according to claim 1, wherein RC1 and RC2 are hydrogen.

### Claim 5 (depends on 1)

A compound according to claim 1, wherein n is 2, X is NRX, and RX is selected from the group consisting of: H; optionally substituted C1-20 alkyl; optionally substituted C5-20 aryl; optionally substituted ester groups; optionally substituted acyl groups; optionally substituted amido groups; optionally substituted thioamido groups; and optionally substituted sulfonyl groups.

### Claim 6 (depends on 1)

A compound according to claim 1, wherein n is 1, X is NRX, and RX is selected from the group consisting of: H; optionally substituted C1-20 alkyl; optionally substituted C5-20 aryl; optionally substituted acyl; optionally substituted sulfonyl; optionally substituted amido; and optionally substituted thioamido groups.

### Claim 7 (depends on 6)

A compound according to claim 6, wherein Het is pyridylene and RX is selected from the group consisting of: optionally substituted acyl; optionally substituted sulfonyl; and optionally substituted amido.

### Claim 8 (depends on 6)

A compound according to claim 6, wherein Het is furanylene or thiophenylene and RX is selected from the group consisting of: optionally substituted C1-20 alkyl; optionally substituted C5-20 aryl; optionally substituted acyl; optionally substituted sulfonyl; and optionally substituted amido.

### Claim 9 (depends on 1)

A compound according to claim 1, wherein n is 1, X is CRXRY, RY is H and RX is selected from the group consisting of: H; optionally substituted C1-20 alkyl; optionally substituted C5-20 aryl; optionally substituted C3-20 heterocyclyl; optionally substituted acyl; optionally substituted amino; optionally substituted amido; and optionally substituted ester groups.

### Claim 10 (depends on 9)

A compound according to claim 9, wherein Het is furanylene or thiophenylene, and RX is selected from optionally substituted amino, wherein the amino groups are selected from H and C1-20 alkyl or together with the nitrogen atom, form a C5-20 heterocyclic group.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.

### Claim 12 (depends on 1)

A method of treatment of disease ameliorated by the inhibition of PARP, comprising administering to a subject in need of treatment a therapeutically-effective amount of a compound according to claim 1 wherein the disease is selected from the group consisting of septic shock; ischemic injury; reperfusion injury; hemorrhagic shock; and multiple sclerosis.