Imidazo(1,2-b)pyridazine derivatives

Claim 2

A compound of formala (IA) wherein R 1 represents an optionally substituted carbocyclic aryl group containing 6 or 10 ring members, an optionally substituted heterocyclic aryl group containing from 5 to 7 atoms in the ring, at least one of which is a heteroatom, the heterocyclic ring optionally being fused to a phenyl ring, or an optionally substituted C 1-10 alkyl C 2-10 alkenyl, C 3-10 cycloalkyl or C3-locycloalkenyl group; R 2 represents an optionally substituted C 1-10 alkyl, C2-loalkenyl, C2-loalkynyl or C3-iocycloalkyl group, a carbocyclic aryl group containing 6 or 10 ring members, an optionally substituted heterocyclic aryl group containing from 5 to 7 atoms in the ring at least one of which is a heteroatom, the heterocyclic ring optionally being fused to a phenyl ring, or an aralkyl group; R 3 represents a hydrogen atom or a C 1 -4alkyl group; and either X represents an oxygen or sulphur atom, a group -CH 2 -, or a group NR 4 where R 4 represents a hydrogen atom or a C 1-4 alkyl group and Y represents a group -CH 2 -, or X-Y together represent the group -CH = CH-; and salts thereof.

Claim 3

A compound as claimed in claim 1 or claim 2 wherein R 1 represents an optionally substituted phenyl or naphthyl group, an optionally substituted 5- or 6- membered heterocyclic aryl group containing from 1 to 4 heteroatoms selected from nitrogen, oxygen, or sulphur, or a C 3 - 6 alkyl group.

Claim 4

A compound as claimed in any of claims 1 to 3 wherein R 2 represents a phenyl group or an optionally substituted C 1 -4alkyl group.

Claim 5

A compound as claimed in any of claims 1 to 4 wherein R 3 represents hydrogen or methyl.

Claim 6

A compound as claimed in any of claims 1 to 5 wherein Y represents -CH 2 -, X represents an oxygen or sulphur atom or -CH 2 - or the group Y-X represents -CH = CH-.

Claim 7

A compound selected from the group comprising: methyl N -[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(3,5-dimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(2,5-dimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N-[6-(1-naphthylmethyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N-[6-(3-methylbenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(2,3-dimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(2,5-dimethylbenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, ethyl N- [6 -(2,5-dimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, ethyl N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methy l N-methyl-N-(6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(2-bromo-3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, n-propy l N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, and n-butyl N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, 2-metho x yethyl N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N-[6-(3,5 - dimethoxy-4-ethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, and physiologically functional derivatives thereof.

Claim 8

A pharmaceutical formulation, comprising a compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof together with a pharmaceutically acceptable carrier therefor.

Claim 9

A compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof for use as an antitumour agent.

Claim 10

Use of a compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof for the manufacture of a medicament for the treatment of tumours.

Claim 11

A process for preparing compounds of general formula (I), which process comprises:- (A) reaction of a pyridazine derivative of general formula (II): (wherein R', and X and Y are as defined in claim 1) with a compound of general formula (III): (wherein R 2 and R 3 are as defined in claim 1 and Z represents a halogen atom); (B) reaction of a pyridazine derivative of general formula (IV): (wherein R 2 and R 3 are as defined in claim 1 and Z 1 represents a leaving group) with a compound of general formula (V): R 1 CH 2 X 1 H (V) (wherein R 1 is as defined in claim 1 and X 1 represents an oxygen or sulphur atom or a group NR 4 as defined in claim 1); (C) reaction of a compound of formula (Vl): ] with an appropriate alcohol R 2 0H (D) reaction of a compound of formula (VII) with a reagent serving to introduce the group -C0 2 R 2 (E) conversion of one compound of formula (I) into another compound of formula (I); followed if desired and/or appropriate by salt formation.

Claim 12

Novel intermediates of formulae (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) and (XI).

Claim 13

Claims for the following Contracting State: ES .+ GR

Claim 14

A process for preparing a compound of general formula (I) wherein R 1 represents an optionally substituted carbocyclic aryl group having 6 or 10 ring members and containing at least one aromatic ring, an optionally substituted heterocyclic aryl group having 5 to 10 ring members, or an optionally substituted C 1-10 alkyl, C 2-10 alkenyl, C 3-10 cycloalkyl or C 3-10 cycloalkenyl group; R 2 represents an optionally substituted Ci-ioalkyl, C 2-10 alkenyl, C2-loalkynyl, C 3-10 cycloalkyl or C 3-10 cycloalkenyl group, an optionally substituted carbocyclic aryl group having 6 or 10 ring members and containing at least one aromatic ring, an optionally substituted heterocyclic group having from 5 to 10 ring members, or an optionally substituted aryl(C 1-4 )alkyl group wherein the aryl portion is a carbocyclic or heterocyclic aryl group as hereinbefore defined; R 3 represents a hydrogen atom or a C 1-4 alkyl group; and either X represents an oxygen or sulphur atom, a group -CH 2 - or a group NR 4 where R 4 represents a hydrogen atom or a C 1-4 alkyl group; and Y represents a group -CH 2 - or -CH 2 CH 2 - or X-Y together represent the group -CH = CH-; and salts and physiologically functional derivatives thereof, which process comprises: (A) reaction of a pyridazine derivative of general formula (II): (wherein R 1 , and X and Y are as defined for formula (I)) with a compound of general formula (III): (wherein R 2 and R 3 are as defined for formula (I)and Z represents a halogen atom); (B) reaction of a pyridazine derivative of general formula (IV): (wherein R 2 and R 3 are as defined for formula (I). and Z 1 represents a leaving group) with a compound of general formula (V): R 1 CH 2 X 1 H (V) (wherein R 1 is as defined for formula (I) and X' represents an oxygen or sulphur atom or a group NR 4 as defined for formula (I)); (C) reaction of a compound of formula (VI): with an appropriate alcohol R 2 0H (D) reaction of a compound of formula (VII) with a reagent serving to introduce the group -CO 2 R 2 (E) conversion of one compound of formula (I) into another compound of formula (I); followed if desired and/or appropriate by salt formation.

Claim 15

A process for preparing compound of formala (IA) wherein R 1 represents an optionally substituted carbocyclic aryl group containing 6 or 10 ring members, an optionally substituted heterocyclic aryl group containing from 5 to 7 atoms in the ring, at least one of which is a heteroatom, the heterocyclic ring optionally being fused to a phenyl ring, or an optionally substituted Ci-ioalkyl C 2 - 10 alkenyl, C 3 - 1 ocycloalkyl or C 3-10 cycloalkenyl group; R 2 represents an optionally substituted C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl or C 3-10 cycloalkyl group, a carbocyclic aryl group containing 6 or 10 ring members, an optionally substituted heterocyclic aryl group containing from 5 to 7 atoms in the ring at least one of which is a heteroatom, the heterocyclic ring optionally being fused to a phenyl ring, or an aralkyl group; R 3 represents a hydrogen atom or a C 1-4 alkyl group; and either X represents an oxygen or sulphur atom, a group -CH 2 -, or a group NR 4 where R 4 represents a hydrogen atom or a C 1-4 alkyl group and Y represents a group -CH 2 -, or X-Y together represent the group -CH = CH-; and salts thereof, which process comprises: (A) reaction of a pyridazine derivative of general formula (II): (wherein R 1 , and X and Y are as defined for formula (IA)) with a compound of general formula (III): (wherein R 2 and R 3 are as defined for formula (IA) and Z represents a halogen atom); (B) reaction of a pyridazine derivative of general formula (IV): (wherein R 2 and R 3 are as defined for formula (IA) and Z' represents a halogen atom) with a compound of general formula (V): R 1 CH 2 X 1 H (V) (wherein R 1 is as defined for formula (IA) and X 1 represents an oxygen or sulphur atom or a group NR 4- as defined for formula (IA)); (C) reaction of a compound of formula (Vl): with an appropriate alcohol R 2 0H (D) conversion of one compound of formula (I) into another compound of formula (I); followed if desired and/or appropriate by salt formation.

Claim 16

A process as claimed in claim 1 for preparing a compound of formula (I) wherein R 1 represents an optionally substituted phenyl or naphthyl group, an optionally substituted 5- or 6- membered heterocyclic aryl group containing from 1 to 4 heteroatoms selected from nitrogen, oxygen or sulphur, or a C 3 - 6 alkyl group.

Claim 17

A process as claimed in claim 1 or claim 3 for preparing a compound of formula (I) wherein R 2 represents a phenyl group or an optionally substituted C 1 - 4 alkyl group.

Claim 18

A process as claimed in any of claims 1, 3 or 4 for preparing a compound of formula (I) wherein R 3 represents hydrogen or methyl.

Claim 19

A process as claimed in any of claims 1 or 3 to 5 for preparing a compound of formula (I) wherein Y represents -CH 2 -, X represents an oxygen or sulphur atom or -CH 2 - or the group Y-X represents -CH = CH-.

Claim 20

A process as claimed in claim 1 for preparing a compound selected from the group comprising: methyl N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(3,5-dimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(2,5-dimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(1-naphthylmethyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(3-methylbenzytoxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(2,3,dimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(2,5-dimethylbenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, ethyl N- [ 6-(2,5-dimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, ethyl N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methy l N-methyl-N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N -[6-(2-bromo-3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, n-propyl N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, and n-butyl N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin- 2-yl]carbamate. 2-methoxyethyl N-[6-(3,4,5-trimethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, methyl N-[6-(3,5 -d imethoxy-4-ethoxybenzyloxy)imidazo[1,2-b]pyridazin-2-yl]carbamate, and physiologically functional derivatives thereof.

Claim 21

A pharmaceutical formulation, comprising a compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof together with a pharmaceutically acceptable carrier therefor.

Claim 22

A process for preparing a pharmaceutical formulation as defined in claim 8 which comprises bringing into association a compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof and a pharmaceutically acceptable carrier therefor.

Claim 23

A compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof for use as an antitumour agent.

Claim 24

Use of a compound of formula (I) or a pharmaceutically acceptable salt or physiologically functional derivative thereof for the manufacture of a medicament for the treatment of tumours.

Claim 25

Novel intermediates of formulae (II), (III), (IV), (V), (VI), (VII), (VIII), (IX), (X) and (XI).