《An exit beyond the pharmacophore model for 5-HT6R agents – a new strategy to gain dual 5-HT6/5-HT2A action for triazine derivatives with procognitive potential》 was written by Kucwaj-Brysz, Katarzyna; Ali, Wesam; Kurczab, Rafal; Sudol-Talaj, Sylwia; Wilczynska-Zawal, Natalia; Jastrzebska-Wiesek, Magdalena; Satala, Grzegorz; Mordyl, Barbara; Zeslawska, Ewa; Agnieszka-Olejarz-Maciej; Czarnota, Kinga; Latacz, Gniewomir; Partyka, Anna; Wesolowska, Anna; Nitek, Wojciech; Handzlik, Jadwiga. Quality Control of 1-Methylpiperazine dihydrochloride And the article was included in Bioorganic Chemistry on April 30 ,2022. The article conveys some information:
Herein, the first highly potent 5-HT6/5-HT2A receptor (5-HT6/5-HT2AR) dual antagonists in a group of 1,3,5-triazine compounds have been discovered as a result of an exit beyond the hydrophobic feature of the pharmacophore model for 5-HT6R antagonists. Design and synthesis of the series I (X = O, S; R1 = 4-PhOC6H4, 4-PhC6H4, 2-naphthyl, 1-naphthyl; R2 = H, Me, Et, n-Bu, R3 = H; R2 = R3 = Me) of ether and thioether derivatives of 1,3,5-triazines with the double-ring aromatic region have been performed. The new compounds I were examined within the comprehensive pharmacol. screening, including: radioligand binding assays, functional and ADMET studies in vitro as well as behavioral tests in rats. Crystallog. aspects and computer-aided structure-activity relationship were analyzed as well. This comprehensive approach led to selection of the compound I [X = S; R1 = 2-naphthyl; R2 = R3 = Me; (II)] with the most significant dual 5-HT6/5-HT2AR antagonistic action (5-HT6R Ki = 11 nM, 5-HT2AR Ki = 39 nM). Moreover, the compound II has satisfactory ADMETox properties in vitro, i.e.: the high permeability through biol. membranes, high metabolic stability, neither mutagenic nor hepatotoxic effects and moderate ability to inhibit CYP3A4. Above all, the compound II showed ability to reverse the pharmacol.-induced (MK-801) memory impairment at low doses (1-3 mg/kg) in Novel Object Recognition (NOR) test in rats. These results indicate a promising potency of dual 5-HT6/5-HT2AR antagonism in the search for novel strategy to fight Alzheimer’s disease, which remains an unmet clin. need. In the experiment, the researchers used 1-Methylpiperazine dihydrochloride(cas: 34352-59-5Quality Control of 1-Methylpiperazine dihydrochloride)
1-Methylpiperazine dihydrochloride(cas: 34352-59-5) is used in the preparation of 2-(4-Methyl-1-piperazinylmethyl)acrylophenone(MPMAP), 1-methylpiperazine-1,4-diium tetrachloridozincate hemihydrate, 2-(4-Methyl-1-piperazinylmethyl)acrylophenone(MPMAP), an antimicrotubular drug..Quality Control of 1-Methylpiperazine dihydrochloride
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics