Patent ID: 7189728

Claim:
A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound selected from compounds of formula 1, tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, tautomers and isomers wherein: X 1 is a methylene group; X 2 is selected from O, S and methylene; X 3 is either NR 5 or a carbonyl or thiocarbonyl group; R 1 is either a hydrogen atom or a nitrile group; R 2 and R 3 are independently selected from H and C 1 –C 6 alkyl, or together may be —(CH 2 ) p —; R 4 is R 4A when X 3 is NR 5 and R 4B when X 3 is a carbonyl or thiocarbonyl group; R 4A is selected from R 6 R 7 NC(═O), R 6 R 7 NC(═S); R 8 (CH 2 ) q C(═O), R 8 (CH 2 ) q C(═S), R 8 (CH 2 ) q OC(═O) and R 8 (CH 2 ) q OC(═S); R 4B is a substituted amino group R 6 R 7 N; R 5 is H or C 1 –C 6 alkyl; R 6 and R 7 are selected independently from R 8 (CH 2 ) q or together they are —(CH 2 ) 2 -Z 1 -(CH 2 ) 2 — or —CHR 9 -Z 2 -CH 2 —CHR 10 —; R 8 is selected from H, C 1 –C 4 alkyl, benzo-fused cyclo(C 1 –C 6 )alkyl, acyl, di(C 1 –C 6 )alkylcarbamoyl, di(C 1 –C 6 )alkylamino, N—(C 1 –C 6 )alkylpiperidyl, optionally substituted aryl, optionally substituted α-(C 1 –C 6 )alkylbenzyl, optionally substituted aroyl, optionally substituted arylsuiphonyl and optionally substituted heteroaryl, wherein heteroaryl means monocyclic five- and six-membered ring aromatic groups with one or two heteroatoms, which are selected from nitrogen, oxygen and sulphur, benzofused derivatives of these rings, and bicyclic groups formed by the fusion of two such monocyclic heteroaromatic groups; R 9 and R 10 are selected independently from H, carbamoyl, hydroxymethyl and cyanomethyl; Z 1 is selected from a covalent bond, —(CH 2 ) r —, —O—, —SO t — and —N((CH 2 ) q R 8 )—; Z 2 is an optionally substituted ortho-phenylene moiety; m is 1–3; n is 0–4; p is 2–5; q is 0–3; r is 1 or 2; and t is 0–2; the optional substituent(s), if present, are selected from the group consisting of (C 1 –C 6 ) alkyl, aryl which may be further substituted with one or more methyl or trifluoromethyl groups, hydroxy, (C 1 –C 6 )alkyloxy, (C 1 –C 6 )alkylsulphonyl, acyl, perfluoroacyl, amino, (C 1 –C 6 )alkylamino, di(C 1 –C 6 )amino, amino(C 1 –C 6 )alkylene, fluoro, chloro, bromo, trifluoromethyl, nitro, cyano, carbamoyl, carboxy, and (C 1 –C 6 )alkyloxycarbonyl groups and/or where two adjacent substituents are present, the two adjacent substituents may be linked so as to form a ring fused to the parent aryl or heteroaryl ring; provided that when X 2 is CH 2 , X 3 is NH and R 4 is R 8 CH 2 O(CO) then R 8 is not unsubstituted phenyl or nitrophenyl; and that when X 1 is CH 2 and R 1 is H and R 4A is R 8 (CH 2 ) q C(═O), then R 8 and q are as defined above but are selected so that R 8 (CH 2 ) q does not represent (C 1 –C 4 )alkyl.