TH68031A - Derivative (Puyido / Thieno) - (F] - Oxacy Pin-5-On - Google Patents

Abstract

DC60 (06/09/45) This invention concerns the derivative of (pyrido/thieno)-[f]-oxazepene-5-one of general formula I (chemical formula) in which R1, R2, and R3 are independently H or (C1-4)alkyl; Ar is a fused thiophene or pyridine ring which may be replaced by one or more substituents chosen from (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy(C1-4)alkyl, CF3, halogen nitrocyanon NR4R5, NR4COR6, and CONR4R5: R4 and R5 are independently H or (C1-4)alkyl, or R4 and R5 are fused with a nitro atom. The binding site forms a saturated 5- or 6-sided heterocyclic ring, which may be given additional heteroatoms selected from O, S, or NR6:R6 as (C1-4)alkyl; A as a residue of the saturated 4-7-sided heterocyclic ring which may be given additional oxygen atoms. The ring may be replaced by 1-3 substitute groups selected from (C1-4)alkyl, (C1-4)alkyloxyhydroxyhalogen, and oxo; or the medicinal salts of such derivatives. This invention also concerns drug formulations containing such derivatives and the use of these (pyrido/thieno)-[f]-oxazepine-5-one derivatives in the treatment of neurological and psychiatric disorders in response to increased synaptic responses mediated by AMPA receptors in the central nervous system. This invention concerns the derivatives. (Pyridone/Thieno)-[F]-oxachepin-5-one, with general formula I (chemical formula), formula I, in which R1, R2, and R3 are independently H or (C1-4)alkyl: Ar is a fused thiophene or pyridine ring which may be replaced by one or more substituted groups chosen from (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy(C1-4)alkyl, CF3, halogen, nitrocyanon, NR4R5, NR4COR6, and CONR4R5: R4 and R5 are independently H or (C1-4)alkyl, or R4 and R5 are combined with the nitrogen atom to which they are bound to form a saturated 5 or 6-sided heterocyclic ring. This may be provided with additional heteroatoms selected from O,S or NR6:R6 is (C1-4)alkyl:A is a residue of a saturated 4-7 hexagonal heterocyclic ring which may be provided with an oxygen atom. The ring may be replaced by 1-3 substitute groups selected from (C1-4)alkyl, (C1-4)alkyloxyhydroxyhalogen and oxo: or therapeutic salts of such derivatives. This invention also concerns drug components containing such derivatives and the use of these (pyrido/thieno)-[f]-oxachepine-5-one derivatives in the treatment of neurological and psychiatric disorders in response to increased synaptic responses mediated by AMPA receptors in the central nervous system.

Claims (7)

1. The derivative (pyrido/thieno)-[f]-oxachepin-5-one with general formula I (chemical formula) in which R1, R2, and R3 are independently H or (C1-4)alkyl Ar is a fused thiophene or pyridine ring which may be replaced by one or more substituted groups chosen from (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy (C1-4)alkyl, CF3, halogen nitrogen, NR4R5, NR4COR6, and CONR4R5. R4 and R5 independently become H or (C1-4)alkyl, or R4 and R5 combine with their bound nitrogen atoms to form a saturated 5- or 6-sided heterocyclic ring, which may have additional heteroatoms selected from O, S, or NR6. R6 is (C1-4)alkyl. A is the residue of a saturated 4-7-sided heterocyclic ring. The oxygen atom may still be present. The ring may be replaced by one to three substituent groups chosen from (C1-4)alkyl, (C1-4)alkyloxyhydroxyhalogen, and oxo, or the medicinal salts of such derivatives, excluding compounds of formula I in which Ar is the pyridin ring attached at the [3,2-F] position; each R1 - R3 group is H and A is (CH2)3. 2. The derivative (pyrido/thieno)-[f]-oxachepin-5-one pursuant to claim 1, where R1, R2 and R3 are H. 3. The derivative (pyridone/thiono)-[f]-oxazepine-5-one under claim 1 or 2, where Ar is a pyridin ring attached at position [3,2-f] or a thiophene ring attached at position [2,3-f]. 4. The derivative (pyrido/thieno)-[f]-oxazepine-5-one with general formula I (chemical formula) in which R1, R2, and R3 are independently H or (C1-4)alkyl Ar is a fused thiophene or pyridine ring which may be replaced by one or more selected first groups. (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy(C1-4)alkyl, CF3, aloe gen nitrogen cyano NR4R5, NR4COR6, and CONR4R5. R4 and R5 independently become H or (C1-4)alkyl, or R4 and R5 combine with their bound nitrogen atoms to form a saturated 5- or 6-sided heterocyclic ring, which may have additional heteroatoms selected from O, S, or NR6. R6 is (C1-4)alkyl. A is the residue of a saturated 4-7-sided heterocyclic ring. The ring, which may still contain an oxygen atom, may be replaced by one to three substituent groups selected from (C1-4)alkyl, (C1-4)alkyloxyhydroxyhalogen, and oxo, or medicinally usable salts of such derivatives for therapeutic use. 5. A medicinal compound containing the derivative (pyrido/thieno)-[f]-oxachepin-5-one formulation I as described in claim 4, together with a medicinally usable carrier. 6. The use of the derivative (pyrido/thieno)-[f]-oxachepine-5-one, formulation I, as described in claim 4, in the preparation of a drug for the treatment of neurological and psychiatric disorders in response to an increase in synaptic responses mediated by AMPA receptors in the central nervous system. 7. Use under claim paragraph 6, which includes diseases or disorders such as neurodegenerative disorders, cognitive impairments, age-related memory and learning disorders, attention disorders, injuries, strokes, epilepsy, Alzheimer's disease, depression, schizophrenia, mental disorders, anxiety disorders, sexual dysfunction, autism, or disorders or diseases caused by psychotropic drugs or substance abuse, and alcohol intoxication.