Benzothiazine and benzothiadiazine compounds

#The present invention relates to new benzothiazine and benzothiadiazine compounds, to a process for their preparation and to pharmaceutical compositions containing them. The compounds of the present invention are new and have very valuable pharmacological properties in respect of AMPA receptors.

#It has now been recognised that the excitatory amino acids, especially glutamate, play a crucial role in the physiological processes of neuronal plasticity and in the mechanisms underlying learning and memory. Pathophysiological studies have clearly shown that a deficit in glutamatergic neurotransmission is closely linked to the development of Alzheimer's disease (Neuroscience and Biobehavioral reviews, 1992, 16, 13-24; Progress in Neurobiology, 1992, 39, 517-545).

#In addition, innumerable works have in recent years demonstrated the existence of sub-types of excitatory amino acid receptors and their functional interactions (Molecular Neuropharmacology, 1992, 2, 15-31).

#More specifically, the present invention relates to compounds of formula (I):

#wherein: R1 represents a hydrogen atom, a halogen atom or a linear or branched (C1-C6)alkyl group, R1a represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, R2 represents a hydrogen atom, a halogen atom or a hydroxy group, A represents a CR4R5 group or an NR4 group, R3 represents a hydrogen atom, a linear or branched (C1-C6)alkyl group or a (C3-C7)cycloalkyl group, R4 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, or A represents a nitrogen atom and, together with the adjacent —CHR3— group, forms the ring

#wherein m represents 1, 2 or 3, R5 represents a hydrogen or halogen atom, X represents an NR6R7, S(O)nR8 or OR′8 group or a heterocyclic group, wherein: R6 represents a hydrogen atom, a linear or branched (C1-C6)alkyl group, S(O)pR9, COR9 or P(O)OR9OR10, R7 represents a hydrogen atom or a linear or branched (C1-C6)alkyl group, or R6 and R7, together with the nitrogen atom carrying them, form a heterocyclic group, R8, R9 and R10, which may be the same or different, represent a hydrogen atom; a linear or branched (C1-C6)alkyl group optionally substituted by one or more halogen atoms; an aryl-(C1-C6)alkyl group in which the alkyl moiety is linear or branched; or an aryl group, R′8 represents a linear or branched (C1-C6)alkyl group or a linear or branched (C1-C6)acyl group, n and p, which may be the same or different, represent 1 or 2, to their enantiomers and diastereoisomers, and also to addition salts thereof with a pharmaceutically acceptable acid or base, it being understood that: a heterocyclic group means a monocyclic or bicyclic, aromatic or non-aromatic group containing from one to four identical or different hetero atoms selected from nitrogen, oxygen and sulphur, optionally substituted by one or more identical or different groups selected from halogen, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)alkoxy, linear or branched (C1-C6)polyhaloalkyl, linear or branched (C1-C6)alkoxy-carbonyl, oxo, thioxo, carboxy, linear or branched (C1-C6)acyl, linear or branched (C1-C6)polyhaloalkoxy, hydroxy, cyano, nitro, amino (optionally substituted by one or more linear or branched (C1-C6)alkyl groups), aminosulphonyl (optionally substituted by one or more linear or branched (C1-C6)alkyl groups) and (C1-C6)alkylsulphonylamino, an aryl group is understood to mean a monocyclic aromatic group or a bicyclic group in which at least one of the rings is aromatic, optionally substituted by one or more identical or different groups selected from halogen, linear or branched (C1-C6)alkyl (optionally substituted by one or more hydroxy groups), linear or branched (C1-C6)alkoxy, linear or branched (C1-C6)polyhaloalkyl, linear or branched (C1-C6)alkoxy-carbonyl, oxo, thioxo, linear or branched (C1-C6)alkylthio, carboxy, linear or branched (C1-C6)acyl, linear or branched (C1-C6)polyhaloalkoxy, hydroxy, cyano, nitro, amino (optionally substituted by one or more linear or branched (C1-C6)alkyl or linear or branched (C1-C6)acyl groups), aminocarbonyl (optionally substituted by one or more linear or branched (C1-C6)alkyl groups), aminosulphonyl (optionally substituted by one or more linear or branched (C1-C6)alkyl groups), mono- or di-((C1-C6)alkylsulphonyl)amino, mono- or di-(trifluoromethylsulphonyl)amino, PO(ORa)(ORb) (wherein Ra and Rb, which may be the same or different, represent a hydrogen atom or a linear or branched (C1-C6)alkyl group), benzyloxy and phenyl (optionally substituted by one or more identical or different groups selected from halogen, linear or branched (C1-C6)alkyl, linear or branched (C1-C6)perhaloalkyl, hydroxy and linear or branched (C1-C6)alkoxy).