| 摘要 |
Azabicyclo [3.2.0] hept-3-yl derivatives (I) and their enantiomers, diastereoisomers, or addition salts with an acid or a base are new. Azabicyclo [3.2.0] hept-3-yl derivatives of formula (I) and their enantiomers, diastereoisomers, or addition salts with an acid or a base are new. ALK : an alkylene chain; W1 : amide group of formula (-NR1a-C(=O)-R) or (-C(=O)-NR1a-R); and R1a, R : H or 1-6C alkyl optionally substituted by one or more groups comprising halo, hydroxy or alkoxy, provided that the alkylene denotes 2-6C divalent radical, and the alkoxy is 1-6C alkyloxy. Independent claims are included for: (1) the preparation of (I); and (2) intermediates comprising alkylene benzoic acid substituted aza-bicycloheptane compounds of formula (VI), alkylene benzoyl chloride substituted aza-bicycloheptane compounds of formula (VII), alkylene benzoic acid ester substituted aza-bicyclo-heptane compounds of formula (VIII), and alkylene oxy phenyl substituted aza-bicyclo-heptane compounds of formula (IX), for preparing (I) (where W1 represents -CONRR1a). R2a : 1-6C alkyl or benzyl. [Image] [Image] - ACTIVITY : Nootropic; Neuroleptic; Neuroprotective; Cerebroprotective; Vulnerary; Hypnotic; Tranquilizer; Antidepressant; CNS-Gen. - MECHANISM OF ACTION : Histamine H3 receptor antagonist. The histamine H3 receptor antagonistic activity of (I) was tested in Naval medical research institute (NMRI) mice. The result showed that 4-{3-[(1R,5S)-3-aza-bicyclo[3.2.0]hept-6-yl]-propoxy}benzamide hydrochloride increased the endogenous cerebral concentration of N-methylhistamine to 100%, at 3 mg/kg. |
