(HETERO)ARYL-SULFONAMIDE DERIVATIVES, THEIR PREPARATION AND THEIR USE AS FACTOR XA INHIBITORS

摘要

A compound of formula (I), or a pharmaceutically-acceptable salt thereof, wherein A is an optionally substituted 5- or 6-membered monocyclic aromatic ring containing 1, 2 or 3 ring heteroatoms selected from oxygen, nitrogen and sulphur; B is optionally substituted phenylene or a 6-membered heterocyclic ring containing 1, 2 or 3 nitrogen heteroatoms; R and R1 are independently selected from hydrogen and (1-4C)alkyl; n is 1 or 2; R2 and R3 are independently selected from hydrogen, (1-6C)alkyl, (4-7C)cycloalkyl, (2-6C)alkenyl or R2 and R3 may form along with the nitrogen to which they are attached a 5-, 6- or 7-membered heterocyclic ring which may contain in addition to the nitrogen atom present 1 or 2 additional heteroatoms selected from nitrogen, oxygen and sulphur, wherein each R2 or R3 group or any heterocyclic ring formed from R2 and R3 may be optionally substituted by hydroxy, amino, carboxy, (1-4C)alkoxycarbonyl, oxo, (1-4C)alkyl, hydroxy-(1-4C)alkyl, (1-4C)alkoxy-(1-4C)alkyl, carboxy-(1-4)alkyl, (1-4C)alkoxycarbonyl-(1-4C)alkyl, or carbamoyl-(1-4C)alkyl; Q is selected from phenyl, naphthyl, phenyl(1-4C)alkyl, phenyl(2-4C)alkenyl and a 5-, 6- or 7-membered heterocyclic ring containing up to 4 heteroatoms selected from nitrogen, oxygen and sulphur wherein Q may be optionally substituted by halo, halo(1-4C)alkyl, cyano, amino, hydroxy, carbamoyl, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkoxy, (2-4C)alkenyloxy, (2-4C)alkynyloxy, (1-4C)alkylthio, (1-4C)alkylsulphinyl, (1-4C)alkylsulphonyl, (1-4C)alkylamino, di(1-4C)alkylamino, (1-4C)alkoxycarbonyl, N-(1-4C)alkylcarbonoyl, (2-6C)alkanoyl, (2-4C)alkanoylamino, hydroxy-(1-4C)alkyl, (1-4C)alkoxy-(1-4C)alkyl, carboxy-(1-4C)alkyl, (1-4C)alkoxycarbonyl-(1-4C)alkyl, carbamoyl-(1-4C)alkyl, N-(1-4C)alkylcarbamoyl-(1-4C)alkyl, N,N-di(1-4C)alkylcarbamoyl-(1-4C)alkyl, phenyl, phenoxy, phenylthio, phenylsulphinyl, phenylsulphonyl, benzyl, benzoyl wherein said phenyl, phenoxy, phenylthio, phenylsulphinyl, phenylsulphonyl, benzyl or benzoyl substituent bears 1, 2 or 3 substituents selected from halo, trifluoromethyl, cyano, hydroxy, amino, nitro, carboxy, carbamoyl, (1-4C)alkyl, (1-4C)alkoxy, (1-4C)alkylamino, di(1-4C)alkylamino, (1-4C)alkoxycarbonyl, N-(1-4C)alkylcarbamoyl, N,N-(1-4C)alkylcarbamoyl and (2-4C)alkenoylamino, which posseses antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention relates to processes for the preparation of the heterocyclic derivative, to pharmaceutical compositions containing them and to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect.