title: Design, synthesis and pharmacological evaluation of 4-(piperazin-1-yl methyl)-N₁-arylsulfonyl indole derivatives as 5-HT₆ receptor ligands.
abstract: 4-(Piperazin-1-yl methyl)-N(1)-arylsulfonyl indole derivatives were designed and synthesized as 5-HT(6) receptor (5-HT(6)R) 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.
authors.affiliation: Discovery Research, Suven Life Sciences Limited, Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500 034, India. nvsrk@suven.com
authors.forename: Ramakrishna V S
authors.initials: RV
authors.lastname: Nirogi
authors.forename: Rajeshkumar
authors.initials: R
authors.lastname: Badange
authors.forename: Ramasastri
authors.initials: R
authors.lastname: Kambhampati
authors.forename: Anil
authors.initials: A
authors.lastname: Chindhe
authors.forename: Amol D
authors.initials: AD
authors.lastname: Deshpande
authors.forename: Vinaykumar
authors.initials: V
authors.lastname: Tiriveedhi
authors.forename: Vishwottam
authors.initials: V
authors.lastname: Kandikere
authors.forename: Nageswararao
authors.initials: N
authors.lastname: Muddana
authors.forename: Renny
authors.initials: R
authors.lastname: Abraham
authors.forename: Mukkanti
authors.initials: M
authors.lastname: Khagga
mesh_terms: D000818:Animals; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008024:Ligands; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles; D008024:Ligands; D011985:Receptors, Serotonin; C097216:serotonin 6 receptor; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A