Design, synthesis and pharmacological evaluation of 4-(piperazin-1-yl methyl)-N1-arylsulfonyl indole derivatives as 5-HT6 receptor ligands

4-(Piperazin-1-yl methyl)-N1-arylsulfonyl indole derivatives were designed and synthesized as 5-HT6 receptor (5-HT6R) ligands. The lead compound 6a, from this series shows potent in vitro binding affinity, good PK profile, no CYP liabilities and activity in animal models of cognition.

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Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2012-12, Vol.22 (24), p.7431-7435
Hauptverfasser:	Nirogi, Ramakrishna V.S., Badange, Rajeshkumar, Kambhampati, Ramasastri, Chindhe, Anil, Deshpande, Amol D., Tiriveedhi, Vinaykumar, Kandikere, Vishwottam, Muddana, Nageswararao, Abraham, Renny, Khagga, Mukkanti
Format:	Artikel
Sprache:	eng
Schlagworte:	5-HT6R ligands Animal models Animals binding capacity Biological and medical sciences chemistry Cognition Cognitive impairment Cross selectivity Cytochrome P-450 CYP2D6 - metabolism Cytochrome P-450 CYP2D6 Inhibitors Cytochrome P-450 CYP3A - metabolism Cytochrome P-450 CYP3A Inhibitors Dose-Response Relationship, Drug Drug Design Enzyme Inhibitors - chemical synthesis Enzyme Inhibitors - chemistry Enzyme Inhibitors - pharmacology HEK293 Cells Humans Indole Indoles - chemical synthesis Indoles - chemistry Indoles - pharmacology Ligands Male Medical sciences Molecular Structure Neuropharmacology Neurotransmitters. Neurotransmission. Receptors ORT Pharmacology. Drug treatments PK profile Rats Rats, Wistar Receptors, Serotonin - metabolism SAR Serotonin S6 receptors Serotoninergic system Structure-Activity Relationship
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Beschreibung
Zusammenfassung:	4-(Piperazin-1-yl methyl)-N1-arylsulfonyl indole derivatives were designed and synthesized as 5-HT6 receptor (5-HT6R) ligands. The lead compound 6a, from this series shows potent in vitro binding affinity, good PK profile, no CYP liabilities and activity in animal models of cognition.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2012.10.057