Identification of 3-sulfonylindazole derivatives as potent and selective 5-HT(6) antagonists

Kevin G Liu; Albert J Robichaud; Alexander A Greenfield; Jennifer R Lo; Cristina Grosanu; James F Mattes; Yanxuan Cai; Guo Ming Zhang; Jean Y Zhang; Dianne M Kowal; Deborah L Smith; Li Di; Edward H Kerns; Lee E Schechter; Thomas A Comery

doi:10.1016/j.bmc.2010.10.033

Identification of 3-sulfonylindazole derivatives as potent and selective 5-HT(6) antagonists

Bioorg Med Chem. 2011 Jan 1;19(1):650-62. doi: 10.1016/j.bmc.2010.10.033. Epub 2010 Oct 20.

Authors

Kevin G Liu¹, Albert J Robichaud, Alexander A Greenfield, Jennifer R Lo, Cristina Grosanu, James F Mattes, Yanxuan Cai, Guo Ming Zhang, Jean Y Zhang, Dianne M Kowal, Deborah L Smith, Li Di, Edward H Kerns, Lee E Schechter, Thomas A Comery

Affiliation

¹ Chemical Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. [email protected]

PMID: 21093272
DOI: 10.1016/j.bmc.2010.10.033

Abstract

As part of our efforts to develop agents for cognitive enhancement, we have been focused on the 5-HT(6) receptor in order to identify potent and selective ligands for this purpose. Herein we report the identification of a novel series of 3-sulfonylindazole derivatives with acyclic amino side chains as potent and selective 5-HT(6) antagonists. The synthesis and detailed SAR of this class of compounds are reported.

MeSH terms

HeLa Cells
Humans
Indazoles / chemistry
Indazoles / pharmacology*
Magnetic Resonance Spectroscopy
Nootropic Agents / chemistry
Nootropic Agents / pharmacology
Receptors, Serotonin / drug effects*
Serotonin Antagonists / chemistry
Serotonin Antagonists / pharmacology*
Spectrometry, Mass, Electrospray Ionization
Structure-Activity Relationship

Substances

Indazoles
Nootropic Agents
Receptors, Serotonin
Serotonin Antagonists
serotonin 6 receptor