Pharmaceutically active pyrazine derivatives

Abstract

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; Qis selected from a bond; C(═O); S(O); SO; and an alkylene chain of 1 to 4 carbon atoms in length between the moiety Rand 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 Calkyl 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 SO, provided that Qcontains no more than one C(═O), S(O), or SOmoiety; Ris selected from hydrogen, methyl, chlorine and bromine; Ris selected from hydrogen, methyl, methoxy and a group —(O)-Q-R; Ris selected from hydrogen, a group Hyd, a group —O-Hydand a group —(O)-Q-R; provided that when one of Rand Ris —(O)-Q-R, the other is selected from hydrogen, methoxy and methyl; and Ris selected from amino, NH-Hyd, N(Hyd); 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 oxidized forms thereof; the carbocyclic or heterocyclic ring being optionally substituted with one or two substituents R. Also provided are pharmaceutical compositions containing the compounds and methods for making the compounds.