- N-Benzhydryloxyethyl-N-phenylpropyl-piperazines
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Piperazine derivatives of the general formula STR1 wherein R1 -R9 are the same or different and each represents a hydrogen or halogen atom or a lower alkyl or lower alkoxy group, n is 2 or 3 and X represents a group (CH2)m (in which m is 1, 2, 3 or 4) or a group --CH2 --CH=CH--, having methylene linked to the piperazine group, and acid addition and quaternary ammonium salts thereof, are described. The compounds exhibit a strong specific dopaminergic activity. Also described are methods for their preparation and use as therapeutic agents in the form of therapeutic compositions.
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- Aryl 1,4-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake
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Substituted 1-[2-(diphenylmethoxy)ethyl]piperazines were synthesized and tested for inhibitory activity on dopamine uptake by synaptosomal preparations of rat corpus striatum. Especially 4-(3-phenyl-2-propenyl)substitution yielded very potent inhibitors with IC50 values of about 1 to 2 nM, activities that surpass that of benztropine 100 times. Compared with other monoamine uptake processes, the effect on dopamine uptake was highly specific. QSAR-analysis showed that substituents in the diphenylmethoxy group combining a strong inductive effect with a small volume provided optimal potency. In contrast, for those in the solitary phenyl group a combination of strong electron-withdrawing effect and a small volume was required.
- Van Der Zee,Koger,Gootjes,Hespe
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p. 363 - 370
(2007/10/02)
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