New heteroaryl derivatives are phosphodiesterase-4 enzyme inhibitors useful for the treatment of e.g. respiratory or gastrointestinal complaints or diseases, depression, Alzheimer's disease and Parkinson's disease

摘要

Heteroaryl derivatives (1) and their racemates, enantiomers, diastereomers, acid addition salts, solvates, hydrates and deuterated forms are new. Heteroaryl derivatives of formula (1) and their racemates, enantiomers, diastereomers, acid addition salts, solvates, hydrates and deuterated forms are new. A : CO, C=NH, 1-6C alkylene or 3-8C cycloalkylene; B 1> : phenyl or an aromatic or non-aromatic ring optionally containing two or three heteroatoms of O, S or N and optionally substituted with OH, O-1-6C alkyl, O-1-6C-haloalkyl, halo, 1-6C alkyl or 1-6C haloalkyl; B 2> : phenyl or hetero aryl containing 2 or 3 heteroatoms of O, S or N; X : e.g. O or S; n : 0-3; either R 1> : e.g. H, 1-6C alkyl, 1-6C haloalkyl; and R 2> : H, 1-6C alkyl or 1-6C haloalkyl; or NR 1>R 2> : non-aromatic heterocycle containing 2 or 3 heteroatoms of O or N; or R 2>+N+A+B 1> : bicyclic group of formula (g); A : CO, C=NH or 1-3C alkyl; m : 1-3; B 1> : sulfonyl compound of formula (h); Z 1> : H, OH, halo, 1-6C alkyl, 1-6C alkanol, O(1-6C alkyl), 6-10C aryl, O-6-10C aryl, NH 2, NH(1-6C alkyl), N(1-6C) alkyl or 3-7C cycloalkyl; and R 4> : e.g. 1-6C alkyl, 3-8C cycloalkyl, 1-6C haloalkyl, CN or halo. Full definitions are given in the DEFINITIONS (Full Definitions) Field. Independent claims are included for: (1) a medicament combination comprising (1) and further active substance, such as beta-mimetic, anticholinergic, corticosteroid, further phosphodiesterase-4-inhibitors, leukotriene D4 antagonists, epidermal growth factor receptor inhibitor, dopamine agonists, H1-antihistaminic, platelet-activating factor antagonist and/or phosphatidylinositol-3 kinase inhibitor; and (2) intermediate compounds of formula (i-iii) or (I-V). PG : H or a suitable protection group; and G : NO 2 or NH 2. [Image] [Image] [Image] [Image] [Image] ACTIVITY : Gastrointestinal-Gen.; Antidepressant; Neuroleptic; Antimanic; Neuroprotective; Nootropic; Antiparkinsonian; Analgesic; Cerebroprotective; CNS-Gen.; Respiratory-Gen.; Antiasthmatic; Antiinflammatory; Antiulcer. MECHANISM OF ACTION : Phosphodiesterase-4 enzyme inhibitor.