PHARMACEUTICALLY ACTIVE PYRAZINE DERIVATIVES

摘要

The invention provides compounds which inhibit or modulate the activity of Chk-1 kinase and which are useful in the treatment of cancer. The compounds have the general formula (1): and salts, N-oxides and tautomers thereof, wherein m is 2, 3 or 4; n is 0 or 1; Q1 is selected from a bond; C(═O); S(O); SO2; and an alkylene chain of 1 to 4 carbon atoms in length between the moiety R4 and the nitrogen atom. N, wherein (a) one or more of the 1 to 4 carbon atoms of the alkylene chain may optionally be substituted with one or two C1-4 alkyl groups; and/or (b) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by a cyclopropane-1,1-diyl or 1,1-cyclobutanediyl group; and/or (c) one carbon atom of the 1 to 4 carbon atoms of the alkylene chain may optionally be replaced by C(═O), S(O), or SO2, provided that Q1 contains no more than one C(═O), S(O), or SO2 moiety; R1 is selected from hydrogen, methyl, chlorine and bromine; R2 is selected from hydrogen, methyl, methoxy and a group—(O)p-Q2-R5; R3 is selected from hydrogen, a group Hyd1, a group—O-Hyd1 and a group—(O)p-Q2-R5; provided that when one of R2 and R3 is—(O)p-Q2-R5, the other is selected from hydrogen, methoxy and methyl; and R4 is selected from amino, NH-Hyd2, N(Hyd2)2; and a non-aromatic carbocyclic or heterocyclic ring of 4 to 7 ring members containing 0, 1, 2 or 3 heteroatom ring members selected from O, N and S and oxidised forms thereof; the carbocyclic or heterocyclic ring being optionally substituted with one or two substituents R9. Also provided are pharmaceutical compositions containing the compounds and methods for making the compounds.