(Pyrido/thieno)-[f]-oxazepine-5-one derivatives
View Patent ↗The present invention relates to (pyrido/thieno)-[f]-oxazepine-5-one derivatives having the general Formula I wherein R 1 , R 2 and R 3 are independently H or (C 1-4 )alkyl; Ar represents a fused thiophene or pyridine ring optionally substituted with one or more substituents selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy, (C 1-4 )alkyloxy(C 1-4 )alkyl, CF 3 , halogen, nitro, cyano, NR 4 R 5 , NR 4 COR 6 , and CONR 4 R 5 ; R 4 and R 5 are independently H or (C 1-4- )alkyl; or R 4 and R 5 form together with the nitrogen atom to which they are bound a 5- or 6-membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O, S or NR 6 ; R 6 is (C 1-4 )alkyl; A represents the residue of a 4-7 membered saturated heterocyclic ring, optionally containing an oxygen atom, the ring being optionally substituted with 1-3 substituents selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy, hydroxy, halogen and oxo; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives, and to the use of these (pyrido/thieno)-[f]-oxazepine-5-one derivatives in the treatment of neurological diseases and psychiatric disorders which are responsive to enhancement of synaptic responses mediated by AMPA receptors in the central nervous system.
1. A compound having the Formula I
wherein
R 1 , R 2 and R 3 are independently H or (C 1-4 )alkyl;
Ar represents a fused thiophene or pyridine ring optionally substituted with one or more substituents selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy, (C 1-4 )alkyloxy(C 1-4 )alkyl, CF 3 , halogen, nitro, cyano, NR 4 R 5 , NR 4 COR 6 , and CONR 4 R 5 ;
R 4 and R 5 are independently H or (C 1-4 )alkyl; or R 4 and R 5 form together with the nitrogen atom to which they are bound a 5- or 6-membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O, S or NR 6 ;
R 6 is (C 1-4 )alkyl;
A represents a C 2 -C 5 group forming a saturated heterocyclic ring, wherein a methylene group may be replaced by an oxygen atom, the ring being optionally substituted with 1-3 substituents selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy, hydroxy, halogen and oxo; or
a pharmaceutically acceptable salt thereof; with the proviso that the compound of formula I wherein Ar is a [3,2-f]fused pyridine ring; each of R 1 -R 3 is H, and A represents (CH 2 ) 3 ; is excluded.
2. The compound of claim 1 , wherein R 1 , R 2 and R 3 are H.
3. The compound of claim 1 or 2 , wherein Ar represents a [3,2-f]fused pyridine or a [2,3-f]-fused thiophene ring.