The influence of 5-HT2A activity on a 5-HT2C specific in vivo assay used for early identification of multiple acting SERT and 5-HT2C receptor ligands

The influence of 5-HT2A activity on a 5-HT2C specific in vivo assay used for early identification of multiple acting SERT and 5-HT2C receptor ligands

Olivér, Éliás; Katalin, Nógrádi; Domány, György; Szakács, Zoltán; János, Kóti; Szántay, Csaba, (ifj.); Tarcsay, Ákos; Keserű, György Mklós; Anikó, Gere; Béla, Kiss; Dalma, Kurkó; Sándor, Kolok; Zsolt, Némethy; Zoltán, Kapui; Virághné Hellinger, Éva; Mónika, Vastag; Katalin, Sághy; Rita, Kedves; Gyertyán, István

Folyóiratcikk

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS vol.:26, issue.:3, p.:914-920.

ISSN: 0960-894X

URI: http://repo.lib.semmelweis.hu//handle/123456789/8077
http://dx.doi.org/10.1016/j.bmcl.2015.12.071

MTMT azonosító: 3021919

WoS ID: 000368797600044

PubMed ID: 26748694

Megjelenés éve: 2016

Kivonat:

As a result of our exploratory programme aimed at elaborating dually acting compounds towards the serotonin (5-HT) transporter (SERT) and the 5-HT2C receptor a novel series of 3-amino-1- phenylpropoxy substituted diphenylureas was identified. From that collection two promising compounds (2 and 3) exhibiting highest 5-HT2C receptor affinity strongly inhibited the 5-HT2C receptor agonist 1-(3-chlorophenyl)piperazine (mCPP) induced hypomotility in mice. In further pursuance of that objective (2- aminoethyl)(benzyl)sulfamoyl diphenylureas and diphenylpiperazines have also been elaborated. Herein we report the synthesis of potent multiple-acting compounds from this new class. However, when two optimized representatives (6 and 14) possessing the desired in vitro profile were tested neither reduced the motor activity of mCPP treated animals. Comparative albeit limited in vitro structure-activity relationship (SAR) analysis and detailed in vivo studies are discussed and explanation for their intricate behaviour is proposed.

Teljes nézet