title: Design, synthesis and pharmacological evaluation of conformationally restricted N-arylsulfonyl-3-aminoalkoxy indoles as a potential 5-HT6 receptor ligands.
abstract: A series of novel conformationally restricted N(1)-arylsulfonyl-3-aminoalkoxy indoles were designed and synthesized as 5-HT(6) receptor (5-HT(6)R) ligands. Many of the synthesized compounds have moderate in vitro-binding affinities at 5-HT(6)R. The lead compound 8b (% inhibition = 97.2 at 1 μM) from this series has good pharmacokinetic profile in male Wister rats and is active in animal model of cognition like Morris water maze. The details of chemistry, SAR, pharmacokinetics and pharmacological data constitute the subject matter of this report.
authors.affiliation: Discovery Research-Medicinal Chemistry, Suven Life Sciences Ltd, Serene Chambers, Banjara Hills, Hyderabad, India. ramakrishna_nirogi@yahoo.co.in
authors.forename: Ramakrishna V S
authors.initials: RV
authors.lastname: Nirogia
authors.forename: Ramasastri
authors.initials: R
authors.lastname: Kambhampati
authors.forename: Anand V
authors.initials: AV
authors.lastname: Daulatabad
authors.forename: Parandhama
authors.initials: P
authors.lastname: Gudla
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shaikh
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Achanta
authors.forename: Anil K
authors.initials: AK
authors.lastname: Shinde
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Dubey
mesh_terms: D000818:Animals; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D023421:Models, Animal; D008968:Molecular Conformation; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D008024:Ligands; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor