958487-83-7Relevant articles and documents
The influence of modifications in imide fragment structure on 5-HT1A and 5-HT7 receptor affinity and in vivo pharmacological properties of some new 1-(m-trifluoromethylphenyl)piperazines
Paluchowska, Maria H.,Bugno, Ryszard,Duszynska, Beata,Tatarczynska, Ewa,Nikiforuk, Agnieszka,Lenda, Tomasz,Chojnacka-Wojcik, Ewa
, p. 7116 - 7125 (2007)
New, flexible (7, 9, 11 and 13) and rigid (8, 10, 12 and 14) imides with a 1-(m-trifluorophenyl)piperazine fragment and a tetramethylene or a 1e,4e-cyclohexylene spacer, respectively, showed very high affinity (Ki = 0.3-34 nM) and agonistic in vivo activity for 5-HT1A receptors. Flexible new compounds and the previously described 5 also bound to 5-HT7 receptors (Ki = 21-134 nM). Selected glutarimide derivatives, that is, the most potent postsynaptic 5-HT1A receptor agonist rigid compound 8 and its flexible analogue 7, as well as the previously described full agonist-rigid compound 6 and the partial agonist-its flexible counterpart 5 exhibited moderate affinity for α1-adrenoceptors (Ki = 85-268 nM), but were practically devoid of any affinity for dopamine D2 sites. Those glutarimides demonstrated anxiolytic- (5 and 7) and antidepressant-like (5, 6 and 8) activity in the four-plate and the swim tests in mice, respectively; at the same time, however, they inhibited the locomotor activity of mice. The antidepressant-like effect of 8 was significantly stronger than that induced by imipramine used as a reference antidepressant.
