QUINOLINE AND QUINOXALINE N-OXIDES AS CHK-1 INHIBITORS

摘要

The invention provides compounds of the formula (1) or salts, solvates or tautomers thereof; wherein Y<SUP>1</SUP> and Y<SUP>2</SUP> are both N<SUP>+</SUP>-O<SUP>-</SUP> or one of Y<SUP>1</SUP> and Y<SUP>2</SUP> is N and the other is N<SUP>+</SUP>-O<SUP>-</SUP>; G is CH<SUB>2</SUB>, O, NH, NHCO or CONH; A is a group (CH<SUB>2</SUB>)<SUB>n</SUB> where n is 1 to 4 provided that when G is O or NH, n is at least 2; Q is N or N<SUP>+</SUP>-O<SUP>-</SUP>; V<SUP>2</SUP> is nitrogen or a group CR<SUP>5</SUP>; V<SUP>3</SUP> is nitrogen or a group CR<SUP>5</SUP>; V<SUP>4</SUP> is nitrogen or CH; provided that no more than two of V<SUP>2</SUP>, V<SUP>3</SUP> and V<SUP>4</SUP> are nitrogen; R<SUP>1</SUP> and R<SUP>2</SUP> are the same or different and each is hydrogen or a substituent R<SUP>6</SUP>; R<SUP>3</SUP> and R<SUP>4</SUP> are the same or different and each is hydrogen or C<SUB>1-4</SUB> alkyl; or R<SUP>3</SUP> and R<SUP>4</SUP> together with the nitrogen atom to which they are attached form an azetidine, pyrrolidine, piperidine, piperazine, N-methylpiperazine or morpholine group; provided that when Q is N<SUP>+</SUP>-O<SUP>-</SUP>, then R<SUP>3</SUP> and R<SUP>4</SUP> are both other than hydrogen; R<SUP>5</SUP> is hydrogen or a substituent R<SUP>6</SUP>; and R<SUP>6</SUP> is as defined in the claims. The compounds of formula (1) are reduced under hypoxic conditions such as those found in solid tumour cells to give compounds that inhibit or modulate Chk-1 kinase.