Novel 5-HT7 receptor inverse agonists. Synthesis and molecular modeling of arylpiperazine-and 1, 2, 3, 4-tetrahydroisoquinoline-based arylsulfonamides

…, M van Smeden, AW Schmidt, JS Sprouse…

Index: Vermeulen, Erik S; van Smeden, Marjan; Schmidt, Anne W; Sprouse, Jeffrey S; Wikstroem, Hakan V; Grol, Cor J Journal of medicinal chemistry, 2004 ,  vol. 47,  # 22  p. 5451 - 5466

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Citation Number: 53

Abstract

A series of arylpiperazine-and 1, 2, 3, 4-tetrahydroisoquinoline-based arylsulfonamides was synthesized and evaluated for their interactions with the constitutively active 5-HT7 receptor. Effects on basal adenylate cyclase activity were measured using HEK-293 cells expressing the rat 5-HT7. All ligands produced a decrease of adenylate cyclase activity, indicative of their inverse agonism. Additionally, computational studies with a set of 22 inverse agonists ...