New substituted naphthalene derivatives are melatonin receptor binders useful e.g. to treat sleep disorders, stress, anxiety, schizophrenia, panic attacks, appetite disorders, obesity, insomnia, epilepsy, diabetes and Parkinson's disease

摘要

Substituted naphthalene derivatives (I) and their enantiomers, diastereoisomers, or acid or base addition salts, are new. Substituted naphthalene derivatives of formula (I) and their enantiomers, diastereoisomers, or acid or base addition salts, are new. R 11-6C (halo)alkyl, 1-6C alkenyl, polyhalo1-6C alkyl, 3-8C cycloalkyl, cyclo(3-8C)alkyl(1-6C)alkyl, (hetero)aryl or 1-6C (hetero)arylalkyl, where aryl is phenyl, naphthyl or biphenyl, heteroaryl is mono or bicyclic aromatic group containing 1-3 heteroatom of O, S or N, and (hetero)aryl is optionally substituted by 1-3 1-6C alkyl, 1-6C alkoxy, OH, COOH, formyl, nitro, CN, halo(1-6C)alkyl, polyhalo1-6C alkyl, alkyloxycarbonyl or halo; and R 2, R 3H or 1-6C alkyl, preferably CH 3. An independent claim is included for preparation of (I). [Image] ACTIVITY : Hypnotic; Tranquilizer; Antidepressant; Cardiovascular-Gen; Gastrointestinal-Gen; CNS-Gen; Muscular-Gen; Neuroleptic; Anorectic; Anticonvulsant; Antidiabetic; Antiparkinsonian; Nootropic; Antimigraine; Neuroprotective; Endocrine-Gen; Cytostatic; Dermatological; Vasotropic; Immunomodulator; Contraceptive; Analgesic. MECHANISM OF ACTION : Melatonin 1 receptor binder; Melatonin 2 receptor binder; 5-Hydroxytryptamine 2c receptor binder. The ability of (I) to bind melatonin 2 receptor was tested using 2-[ 125I]-iodomelatonin radioligand. The result showed that inhibitory constant of N-{2-[3-(1-hydroxyethyl)-7-methoxy-1-naphthyl]ethyl}acetamide was 3 nM.