Novel naphthalene derivatives, process for the preparation thereof and pharmaceutical compositions containing same

• Main Authors: PHILIPPE DELAGRANGE, MARK MILLAN, MOHAMED ETTAOUSSI, MICHAEL SPEDDING, AHMED SABAOUNI, PASCAL BERTHELOT, SAID YOUS, DANIEL-HENRI CAIGNARD
• Format: Patent
• Language: English
• Published: 19.02.2009
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

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, polyhalo(1-6C)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 O, S or N, and (hetero)aryl is optionally substituted by 1-3 group comprising 1-6C alkyl, 1-6C alkoxy, OH, carboxy, formyl, nitro, CN, halo(1-6C)alkyl, 1-6C polyhaloalkyl, alkyloxycarbonyl or halo; X : oxime NOR 2, which can be in Z or E configuration; and R 2H or 1-6C alkyl, preferably CH 3. An independent claim is included for the 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-[ 125>I]-iodomelatonin radioligand. The result showed that inhibitory constant of N-[(2E)-2-(hydroxyimino)-2-(7-methoxy-1-naphthyl)ethyl]acetamide was 0.8 nM.