An exit beyond the pharmacophore model for 5-HTR agents - a new strategy to gain dual 5-HT/5-HT action for triazine derivatives with procognitive potential.

This research allowed us to find the first highly potent 5-HT/5-HT receptor (5-HT/5-HTR) dual antagonists in a group of 1,3,5-triazine compounds as a result of an exit beyond the hydrophobic feature of the pharmacophore model for 5-HTR antagonists. Design and synthesis of the series (2-16) of new O- and S-containing ether derivatives of 1,3,5-triazines with the double-ring aromatic region have been performed. The new compounds were examined within the comprehensive pharmacological screening, including: radioligand binding assays, functional and ADMET studies in vitro as well as behavioral tests in rats.

The Structural Determinants for α-Adrenergic/Serotonin Receptors Activity among Phenylpiperazine-Hydantoin Derivatives.

Several studies confirmed the reciprocal interactions between adrenergic and serotoninergic systems and the influence of these phenomena on the pathogenesis of anxiety. Hence, searching for chemical agents with a multifunctional pharmacodynamic profile may bring highly effective therapy for CNS disorders. This study presents a deep structural insight into the hydantoin-arylpiperazine group and their serotonin/α-adrenergic activity.

Chemical update on the potential for serotonin 5-HT and 5-HT receptor agents in the treatment of Alzheimer's disease.

Despite the better understanding of the mechanisms underlying Alzheimer's Disease (AD) and launched clinical trials, no AD-modifying treatment based on a synthetic drug has been introduced for almost twenty years. The serotonin 5-HT and 5-HT receptors turned out to be promising biological targets for modulation of central nervous system dysfunctions including cognitive impairment. Within this paper, we evaluate the pharmacological potency of both, 5-HTR and 5-HTR, agents in search for novel AD treatment.

Application of bioorthogonal hetero-Diels-Alder cycloaddition of 5-arylidene derivatives of 1,3-dimethylbarbituric acid and vinyl thioether for imaging inside living cells.

New bioorthogonal cycloaddition of 5-arylidene derivatives of 1,3-dimethylbarbituric acid as 1-oxa-1,3-butadienes and vinyl thioether as a dienophile has been applied to imaging inside living cells. The reaction is high yielding, selective, and fast in aqueous media. The proposed 1-oxa-1,3-butadiene derivative conjugated to a FITC fluorochrome selectively and rapidly labels the cancer cells pretreated with the dienophile-taxol.