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

Bioorganic & Medicinal Chemistry
2007.0

Abstract

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 (K(i)=0.3-34 nM) and agonistic in vivo activity for 5-HT(1A) receptors. Flexible new compounds and the previously described 5 also bound to 5-HT(7) receptors (K(i)=21-134 nM). Selected glutarimide derivatives, that is, the most potent postsynaptic 5-HT(1A) 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 alpha(1)-adrenoceptors (K(i)=85 - 268 nM), but were practically devoid of any affinity for dopamine D(2) 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.

Knowledge Graph

Similar Paper

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
Bioorganic & Medicinal Chemistry 2007.0
Polycyclic aryl- and heteroarylpiperazinyl imides as 5-HT1A receptor ligands and potential anxiolytic agents: synthesis and structure-activity relationship studies
Journal of Medicinal Chemistry 1988.0
Antidepressant- and anxiolytic-like activity of 7-phenylpiperazinylalkyl-1,3-dimethyl-purine-2,6-dione derivatives with diversified 5-HT1A receptor functional profile
Bioorganic & Medicinal Chemistry 2015.0
Synthesis and pharmacological evaluation of new 5-(cyclo)alkyl-5-phenyl- and 5-spiroimidazolidine-2,4-dione derivatives. Novel 5-HT1A receptor agonist with potential antidepressant and anxiolytic activity
European Journal of Medicinal Chemistry 2010.0
Synthesis and serotonin receptor activity of the arylpiperazine alkyl/propoxy derivatives of new azatricycloundecanes
European Journal of Medicinal Chemistry 2009.0
Synthesis and Structure−Activity Relationships of a New Model of Arylpiperazines. 4. 1-[ω-(4-Arylpiperazin-1-yl)alkyl]-3-(diphenylmethylene)- 2,5-pyrrolidinediones and -3-(9H-fluoren-9-ylidene)-2,5-pyrrolidinediones: Study of the Steric Requirements of the Terminal Amide Fragment on 5-HT<sub>1A</sub> Affinity/Selectivity
Journal of Medicinal Chemistry 1999.0
New Arylpiperazine 5-HT<sub>1A</sub>Receptor Ligands Containing the Pyrimido[2,1-f]purine Fragment:  Synthesis, in Vitro, and in Vivo Pharmacological Evaluation
Journal of Medicinal Chemistry 2004.0
New (2-Methoxyphenyl)piperazine Derivatives as 5-HT1A Receptor Ligands with Reduced .alpha.1-Adrenergic Activity. Synthesis and Structure-Affinity Relationships
Journal of Medicinal Chemistry 1995.0
Novel class of arylpiperazines containing N-acylated amino acids: Their synthesis, 5-HT1A, 5-HT2A receptor affinity, and in vivo pharmacological evaluation
Bioorganic &amp; Medicinal Chemistry 2007.0
SAR-studies on the importance of aromatic ring topologies in search for selective 5-HT7 receptor ligands among phenylpiperazine hydantoin derivatives
European Journal of Medicinal Chemistry 2014.0