Synthesis and Biological Evaluation of Benzodioxanylpiperazine Derivatives as Potent Serotonin 5-HT sub(1A) Antagonists: The Discovery of Lecozotan

Synthesis and Biological Evaluation of Benzodioxanylpiperazine Derivatives as Potent Serotonin 5-HT sub(1A) Antagonists: The Discovery of Lecozotan

A series of benzodioxanylpiperazine derivatives possessing a 4-aryl amide substituent was prepared and evaluated for 5-HT sub(1A) affinity and functional antagonist activity in vitro and in vivo. All of the compounds in this series possessed high affinity for the human 5-HT sub(1A) receptor and many...

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Veröffentlicht in:Journal of medicinal chemistry 2005-05, Vol.48 (10), p.3467-3470
Hauptverfasser: Childers, WE Jr, Abou-Gharbia, MA, Kelly, M G, Andree, TH, Harrison, B L, Ho, D M, Hornby, G, Huryn, D M, Potestio, L, Rosenzweig-Lipson, S J, Schmid, J, Smith, D L, Sukoff, S J, Zhang, G, Schechter, LE
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container_end_page 3470
container_issue 10
container_start_page 3467
container_title Journal of medicinal chemistry
container_volume 48
creator Childers, WE Jr
Abou-Gharbia, MA
Kelly, M G
Andree, TH
Harrison, B L
Ho, D M
Hornby, G
Huryn, D M
Potestio, L
Rosenzweig-Lipson, S J
Schmid, J
Smith, D L
Sukoff, S J
Zhang, G
Schechter, LE
description A series of benzodioxanylpiperazine derivatives possessing a 4-aryl amide substituent was prepared and evaluated for 5-HT sub(1A) affinity and functional antagonist activity in vitro and in vivo. All of the compounds in this series possessed high affinity for the human 5-HT sub(1A) receptor and many displayed potent antagonist activity in vitro and varying degrees of intrinsic activity in vivo. Compound 11c (Lecozotan) was selected for further development and is currently in clinical trials.
doi_str_mv 10.1021/jm049493z
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title Synthesis and Biological Evaluation of Benzodioxanylpiperazine Derivatives as Potent Serotonin 5-HT sub(1A) Antagonists: The Discovery of Lecozotan
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