title: Design, synthesis and pharmacological evaluation of indolylsulfonamide amines as potent and selective 5-HT6 receptor antagonists.
abstract: A series of N'-[3-(indole-1-sulfonyl) aryl]-N,N-dimethyl ethane-1,2-diamines and N'-[3-(indole-1-sulfonyl) aryl]-N,N-dimethyl propane-1,3-diamines was designed and synthesized as 5-HT6 receptor ligands. These compounds, when screened in a functional reporter gene-based assay, displayed potent antagonistic activity with Kb values in the range of 1.8-60 nM. The lead compound 9y has shown good ADME surrogate properties, acceptable pharmacokinetic profile and is active in animal models of cognition like novel object recognition test and Morris water maze. It was selected for detailed profiling.
authors.affiliation: Discovery Research-Medicinal Chemistry, Suven Life Sciences Limited, Serene Chambers , Banjara Hills, Hyderabad , India and.
authors.forename: Ramakrishna V S
authors.initials: RV
authors.lastname: Nirogi
authors.forename: Thrinath Reddy
authors.initials: TR
authors.lastname: Bandyala
authors.forename: Veena
authors.initials: V
authors.lastname: Reballi
authors.forename: Jagadishu Babu
authors.initials: JB
authors.lastname: Konda
authors.forename: Anand V
authors.initials: AV
authors.lastname: Daulatabad
authors.forename: Mukkanti
authors.initials: M
authors.lastname: Khagga
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D016466:CHO Cells; D003412:Cricetulus; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D013550:Swimming
chemical_list: D000588:Amines; D007211:Indoles; D008024:Ligands; D011985:Receptors, Serotonin; D011994:Recombinant Proteins; D012702:Serotonin Antagonists; D013449:Sulfonamides; C097216:serotonin 6 receptor; D008156:Luciferases
keywords: 5-Hydroxytryptamine6 receptor; central nervous system; cognition; novel object recognition test; structure activity relationship; water maze