AMINOHETEROARYL COMPOUNDS AS FOR THE TREATMENT OF DISEASES MEDIATED BY C-MET KINASE ACTIVITY

摘要

Compounds of formula (I), are inhibitors of c-Met kinase activity, useful inter alia in the treatment of hyperproliferative diseases: wherein X is -N= or -CH=; ring A is optionally substituted mono- or bi-cyclic aryl or heteroaryl having from 5 to 12 ring atoms; ring B is (i) optionally substituted phenyl, (ii) optionally substituted monocyclic heterocyclic having 5 or 6 ring atoms and having one or two nitrogens as the sole ring heteroatoms, (iii) optionally substituted bicyclic ring system of 9 or 10 ring atoms having one two or three ring nitrogens and optionally a ring oxygen as the sole ring heteroatoms; R<SUB>2</SUB> is selected from hydrogen, halogen, (C<SUB>1</SUB>-C<SUB>6</SUB>)alkyl, (C<SUB>2</SUB>-C<SUB>6</SUB>)alkenyl, (C<SUB>3</SUB>-C<SUB>6</SUB>)cycloalkyl, and mono- or bi-cyclic heterocyclic having from 5 to 12 ring atoms, R<SUB>3</SUB> and R<SUB>4</SUB> are (a) independently selected from hydrogen, halogen, (C<SUB>1</SUB>-C<SUB>6</SUB>)alkyl, (C<SUB>2</SUB>-C<SUB>6</SUB>)alkenyl, (C<SUB>3</SUB>-C<SUB>6</SUB>)cycloalkyl, and mono- or bi-cyclic heterocyclic having from 5 to 12 ring atoms; or (b) R<SUB>3</SUB> and R<SUB>4</SUB> taken together with the carbon to which they are attached form a (C<SUB>3</SUB>-C<SUB>6</SUB>)cycloalkyl ring; or (c) one of R<SUB>3</SUB> and R<SUB>4</SUB> is as defined in case (a) while the other is a divalent radical selected from -(CH<SUB>2</SUB>)<SUB>3</SUB>- or -(CH<SUB>2</SUB>)<SUB>4</SUB>- in which one or two non-adjacent carbons are replaced by oxygen, sulfur or -NR<SUB>3</SUB>- wherein Ra is hydrogen or (C<SUB>1</SUB>-C<SUB>3</SUB>) alkyl; R<SUB>5</SUB> is hydrogen and R<SUB>6</SUB> is a radical of formula (IA), or R<SUB>6</SUB> is hydrogen and R<SUB>5</SUB> is a radical of formula -(Z<SUP>1</SUP>)<SUB>w</SUB>-(CH<SUB>2</SUB>)<SUB>Z</SUB>-L<SUP>1</SUP>-Y<SUP>1</SUP>-CH(R<SUB>7</SUB>)-NHR<SUB>8</SUB> wherein R<SUB>7</SUB> is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; and R<SUB>8</SUB> is hydrogen; or optionally substituted (C<SUB>1</SUB>-C<SUB>6</SUB>)alkyl, (C<SUB>3</SUB>-C<SUB>7</SUB>)cycloalkyl, aryl or heteroaryl Or -(C=O)R<SUB>9</SUB>, -(C=O)OR<SUB>9</SUB>, Or -(C=O)NR<SUB>9</SUB> wherein R<SUB>9</SUB> is hydrogen or optionally substituted (C<SUB>1</SUB>-C<SUB>6</SUB>)alkyl; and -(Z<SUP>1</SUP>)<SUB>w</SUB>-(CH<SUB>2</SUB>)<SUB>Z</SUB>-L<SUP>1</SUP>-Y<SUP>1</SUP>- is a linker radical as defined in the claims.