title: Synthesis and structure-activity relationship of novel conformationally restricted analogues of serotonin as 5-HT6 receptor ligands.
abstract: 5-Hydroxytryptamine 6 receptors (5-HT(6)R) are being perceived as the possible target for treatment of cognitive disorders as well as obesity. The present article deals with the design, synthesis, in vitro binding and structure-activity relationship of a novel series of tetracyclic tryptamines with the rigidized N-arylsulphonyl, N-arylcarbonyl and N-benzyl substituents as 5-HT(6) receptor ligands. The chiral sulphonyl derivatives 15a and 17a showed high affinity at 5-HT(6)R with the K(i) of 23.4 and 20.5 nM, respectively. The lead compound from the series 15a has acceptable ADME properties, adequate brain penetration and is active in animal models of cognition like Novel Object Recognition Task (NORT) and water maze.
authors.affiliation: Discovery Research-Medicinal Chemistry, Suven Life Sciences Ltd., Banjara Hills, Hyderabad, India. ramakrishna_nirogi@yahoo.co.in
authors.forename: Ramakrishna V S
authors.initials: RV
authors.lastname: Nirogi
authors.forename: Ramasastri
authors.initials: R
authors.lastname: Kambhampati
authors.forename: Prabhakar
authors.initials: P
authors.lastname: Kothmirkar
authors.forename: Jagadishbabu
authors.initials: J
authors.lastname: Konda
authors.forename: Thrinath Reddy
authors.initials: TR
authors.lastname: Bandyala
authors.forename: Parandhama
authors.initials: P
authors.lastname: Gudla
authors.forename: Sobhanadri
authors.initials: S
authors.lastname: Arepalli
authors.forename: Narasimhareddy P
authors.initials: NP
authors.lastname: Gangadasari
authors.forename: Anil K
authors.initials: AK
authors.lastname: Shinde
authors.forename: Amol D
authors.initials: AD
authors.lastname: Deshpande
authors.forename: Adireddy
authors.initials: A
authors.lastname: Dwarampudi
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chindhe
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Dubey
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008968:Molecular Conformation; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor; D012701:Serotonin