[3-[(1-Methylpiperidin-4-yl) methyl] arylsulfonyl]-1H-indoles: Synthesis, SAR and biological evaluation as a novel class of 5-HT6 Receptor Antagonists

• Published in: Journal of chemical sciences (Bangalore, India) Vol. 127; no. 3; pp. 439 - 445
• Main Authors: NIROGI, RAMAKRISHNA V S, BADANGE, RAJESH KUMAR, KANDUKURI, KIRAN KUMAR, KHAGGA, MUKKANTI
• Format: Journal Article
• Language: English
• Published: New Delhi Springer India 01.03.2015
• Subjects: Chemistry; Chemistry and Materials Science; Chemistry/Food Science; indoles; pharmacokinetic profile; R antagonists; cross selectivity; [3-[(1-Methylpiperidin-4-yl) methyl] arylsulfonyl]-1; cognitive impairment; structure activity relationship; 5-HT
• ISSN: 0974-3626; 0973-7103
• DOI: 10.1007/s12039-015-0800-7

In continuation to our efforts to develop better treatment options for cognitive decline, we have been focussing on 5-HT 6 receptor (5-HT 6 R) antagonists, which are known to be involved in improving cognitive function in numerous animal models. In this paper, we report a novel series of [3-[(1-Methylpiperidin-4-yl) methyl] arylsulfonyl]-1 H -indole derivatives as potent and selective 5-HT 6 R antagonists. The lead compound from this series shows potent in vitro binding affinity, functional antagonistic activity at 5-HT 6 R, good pharmacokinetic profile, excellent selectivity and no Cytochrome P450 liabilities. Graphical Abstract We report a novel series of [3-[(1-Methylpiperidin-4-yl) methyl] arylsulfonyl]-1 H -indole derivatives as potent and selective 5-HT 6 R antagonists. The lead compound from this series shows potent in vitro binding affinity, functional antagonistic activity at 5-HT 6 R, good pharmacokinetic profile, excellent selectivity and no CYP liabilities.