Design of novel multiple-acting ligands towards SERT and 5-HT2C receptors.
This Letter describes our attempts to elaborate dually acting compounds possessing serotonin re-uptake transporter inhibitor and serotonin 5-HT2C receptor antagonist properties. A novel series of 1,3-diphenylureas and N-phenylbenzamides have thus been prepared and evaluated. Based on its in vitro and in vivo activities, as well as pharmacokinetic profile, compound 16a was identified as a lead compound. The synthesis and structure-activity relationship of this series of compounds is presented herein.
Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary. Electronic address: elias@richter.hu.
Olivér
O
Eliás
Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
Eva
E
Agai-Csongor
Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
György
G
Domány
Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
György Miklós
GM
Keserű
Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
Anikó
A
Gere
Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
Béla
B
Kiss
Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
Eva
E
Hellinger
Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
Mónika
M
Vastag
Gedeon Richter Plc, Budapest 10, PO Box 27, H-1475, Hungary.
István
I
Gyertyán
D000818:Animals; D001549:Benzamides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D002224:Carbanilides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001549:Benzamides; D002224:Carbanilides; D008024:Ligands; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists
5-HT(2C) antagonist; Designed multiple ligands; SERT inhibitor