Phthalazinone derivatives
View Patent ↗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: —(CH 2 ) n1 -Q n2 -(CH 2 ) n3 — wherein n 1 , n 2 and n 3 are each selected from 0, 1, 2 and 3, the sum of n 1 , n 2 and n 3 is 1, 2 or 3 and Q is selected from O, S, NH, C(═O) or —CR 1 R 2 —, where R 1 and R 2 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 R 1 and R 2 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 R 1 and R 2 are attached in Q, —(CH 2 ) 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.
1. A compound of formula:
or an isomer, salt, solvate, chemically protected form, and prodrug thereof, wherein:
A and B together represent optionally monosubstituted, fused benzene;
R C is —CH 2 —R L ;
R L is substituted phenyl, wherein the substituents are selected from the group consisting of:
C 3-20 heterocyclyl; ester; amido; acyloxy; sulfonamido; ureido; and optionally further substituted; and
R N is hydrogen.
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:
or an isomer, salt, solvate, chemically protected form, and prodrug thereof, wherein:
A and B together represent an optionally substituted, fused benzene;
R C is —CH 2 —R L ;
R L is optionally substituted phenyl; and
R N is hydrogen;
and a pharmaceutically acceptable carrier or diluent.
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:
or an isomer, salt, solvate, chemically protected form and prodrug thereof.