5-methyl-8-N-substituted-thiocarbamoyl-7,8-diazabicyclo[4.3.0] non-6-enes: evaluation as BSAO inhibitors and pharmacological activity screening.
In this study a series of 5-methyl-8-N-substituted-thiocarbamoyl-7,8-diazabicyclo[4.3.0] non-6-enes derivatives previously synthesized and separated to their stereoisomers, were evaluated as BSAO inhibitors and screened pharmacologically for antidepressant activity, effect on anxiety and experimental parkinsonism by in vivo tests. The title compounds caused 30-40% inhibition irrespective of geometric isomerism as well as nature of substituent. On the other hand, their open chain derivative NBE (4-ethyl, p-methoxybenzylidenthiosemicarbazide) showed a marked enzyme inhibition and antidepressant effect. While the other group was inactive as antidepressant effect, these compounds have shown diastereoselective antitremor activity by inhibiting the tremors induced by oxotremorin in mice pretreated with dopaminergic antagonist haloperidol. The title compounds constitutes a new class of BSAO inhibitors and may serve as usefull leads for further investigation as specific BSAO inhibitors, antiparkinson, antidepressant and anticholinergic agents.
Yeşilada
A
A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Gökhan
N
N
Ozer
I
I
Vural
K
K
Erol
K
K
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000978:Antiparkinson Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002417:Cattle; D005260:Female; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D018721:Muscarinic Agonists; D010095:Oxotremorine; D051381:Rats; D013859:Thiocarbamates / Q000138:chemical synthesis* / Q000494:pharmacology; D014202:Tremor / Q000139:chemically induced / Q000517:prevention & control
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D000978:Antiparkinson Agents; D007093:Imidazoles; D008996:Monoamine Oxidase Inhibitors; D018721:Muscarinic Agonists; D013859:Thiocarbamates; D010095:Oxotremorine