Identification of 3-sulfonylindazole derivatives as potent and selective 5-HT6 antagonists

• Published in: Bioorganic & medicinal chemistry Vol. 19; no. 1; pp. 650 - 662
• Main Authors: Liu, Kevin G., Robichaud, Albert J., Greenfield, Alexander A., Lo, Jennifer R., Grosanu, Cristina, Mattes, James F., Cai, Yanxuan, Zhang, Guo Ming, Zhang, Jean Y., Kowal, Dianne M., Smith, Deborah L., Di, Li, Kerns, Edward H., Schechter, Lee E., Comery, Thomas A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.01.2011; Elsevier
• Subjects: 5-HT; 5-HT6; 5-Hydroxytryptamine; 5-Hydroxytryptamine-6; Alzheimer’s disease; antagonists; Biological and medical sciences; chemistry; Cognition; Cognitive dysfunction; Cognitive impairment; Medical sciences; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Schizophrenia; Serotonin; Serotoninergic system; 5-Hydroxytryptamine; 5-HT6; Serotonin; Alzheimer’s disease; 5-Hydroxytryptamine-6; Schizophrenia; Cognition; 5-HT; Cognitive dysfunction; Cognitive impairment; Cognitive disorder; CNS stimulant; Alzheimer disease; Psychotropic; 5-HT6 serotonin receptor; Selectivity; Indazole derivatives; Structure activity relation; Neurotransmitter; Antagonist; Chemical synthesis; Alzheimer's disease
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2010.10.033

As part of our efforts to develop agents for cognitive enhancement, we have been focused on the 5-HT6 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-HT6 antagonists. The synthesis and detailed SAR of this class of compounds are reported.