Discovery of a Novel 5-HT3 Antagonist/5-HT1A Agonist 3-Amino-5, 6, 7, 8-tetrahydro-2-{4-[4-(quinolin-2-yl) piperazin-1-yl] butyl} quinazolin-4 (3 H)-one (TZB-30878) …

…, H Hayashi, S Tamaoki, Y Yamauchi…

Index: Asagarasu, Akira; Matsui, Teruaki; Hayashi, Hiroyuki; Tamaoki, Satoru; Yamauchi, Yukinao; Minato, Kouichi; Sato, Michitaka Journal of Medicinal Chemistry, 2010 , vol. 53, # 21 p. 7549 - 7563

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Citation Number: 13

Abstract

We have prepared a series of quinazolinone derivatives linked with piperazinylquinoline for the treatment of irritable bowel syndrome (IBS). Using pharmacophore analysis, we designed and synthesized compounds which bind to both serotonin receptor subtype 1A (5- HT1A) and subtype 3 (5-HT3). Quinazolinone derivatives with a sulfur atom in the linker showed high affinity in in vitro assays, but low in vivo activity. Focusing on the linker to ...