Phthalazinone derivatives

• US 7,151,102 B2
• Filed: 10/30/2001
• Issued: 12/19/2006
• Est. Priority Date: 10/30/2000
• Status: Expired due to Term

• Current Assignee: Kudos Pharmaceuticals Limited (Astrazeneca PLC)
• Original Assignee: Kudos Pharmaceuticals Limited (Astrazeneca PLC), Maybridge PLC
• Inventors: Smith, Graeme Cameron Murray, Martin, Niall Morrison Barr, Vile, Julia, Douglas, Diane Gillian, Eversley, Penny Jane, Newton, Roger Frank, White, Charles Richard
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): Ward, Paul V.
• Application Number:
  US10/021,506
• Publication Number:
  US 20020183325A1
• Time in Patent Office: 1,876 Days
• Field of Search: 514/248, 514/252.01, 514/252.02, 514/252.03, 514/252.04, 514/252.05, 514/252.06, 544/234, 544/235, 544/237, 544/233
• US Class Current: 514/248
• CPC Class Codes: A61K 31/50 Pyridazines; Hydrogenated pyridazines
• CPC Class Codes: A61K 31/502 ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
• CPC Class Codes: C07D 237/32 with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

A method of treatment of a disease of the human or animal body mediated by PARP comprising administering to such a subject a therapeutically effective amount of a compound of formula:

or an isomer, salt, solvate, chemically protected form, and prodrug thereof, wherein:

• A and B together represent an optionally substituted, fused aromatic ring;
• R_C is represented by —L—R_L, where L is of formula:
  —(CH₂)_n1-Q_n2-(CH₂)_n3—
  wherein n₁, n₂ and n₃ are each selected from 0, 1, 2 and 3, the sum of n₁, n₂ and n₃ is 1, 2 or 3 and Q is selected from O, S, NH, C(═O) or —CR₁R₂—, where R₁ and R₂ are independently selected from hydrogen, halogen or optionally substituted C_1-7 alkyl, or may together with the carbon atom to which they are attached form a C_3-7 cyclic alkyl group, which may be saturated (a C_3-7 cycloalkyl group) or unsaturated (a C_3-7 cycloalkenyl group), or one of R₁ and R₂ may be attached to an atom in R_L to form an unsaturated C_3-7 cycloalkenyl group which comprises the carbon atoms to which R₁ and R₂ are attached in Q, —(CH₂)_n3— (if present) and part of R_L;
• and R_L is optionally substituted C_5-20 aryl; and
• R_N is selected from hydrogen, optionally substituted C_1-7 alkyl, C_3-20 heterocyclyl, and C_5-20 aryl, hydroxy, ether, nitro, amino, amido, thiol, thioether, sulfoxide and sulfone.

Claims

1. A compound of formula:

2. A compound according to claim 1, wherein the fused benzene is unsubstituted.

3. A compound according to claim 1, wherein R_L is substituted by a ureido group, or a sulfonamido group.

4. A pharmaceutical composition comprising a compound of formula:

5. The pharmaceutical composition of claim 4, wherein the fused benzene is unsubstituted.

6. The pharmaceutical composition of claim 4, wherein R_L is substituted by one or more substituents selected from the group consisting of:

C_1-7 alkyl;

C_5-20 aryl;

C_3-20 heterocyclyl;

halo;

hydroxy;

ether;

nitro;

cyano;

carbonyl groups;

amino;

sulfonamido;

ureido;

acyloxy;

thiol;

thioether;

sulfoxide; and

sulfone.

7. The pharmaceutical composition of claim 6, wherein R_L is substituted by a ureido group, or a sulfonamido group.

8. A compound of the formula: