title: Rigidized 1-aryl sulfonyl tryptamines: synthesis and pharmacological evaluation as 5-HT6 receptor ligands.
abstract: A series of N(1)-arylsulfonyl-3-(pyrrolidin-3-yl)-1H-indole and N(1)-arylsulfonyl-3-(4-chloro-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole derivatives (tryptamine derivatives with rigidized side chain) have been prepared and tested for their binding affinity to 5-HT(6) receptor. Several compounds displayed potent binding affinity for the 5-HT(6) receptor when tested in in vitro binding assay. The primary SAR indicates that rigidification of dimethylamino alkyl chain at C(3) of indole carbon maintains the binding affinity to 5-HT(6)R. The lead compound N(1)-benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a (K(b)=0.1 nM) has shown excellent in vitro affinity and was active in animal models of cognition like NORT and water maze.
authors: Discovery Research, Suven Life Sciences Ltd., Serene Chambers, Banjara Hills, Hyderabad, India. ramakrishna_nirogi@yahoo.co.in
authors: Ramakrishna
authors: R
authors: Nirogi
authors: Adireddy
authors: A
authors: Dwarampudi
authors: Ramasastry
authors: R
authors: Kambhampati
authors: Venugopalarao
authors: V
authors: Bhatta
authors: Laxman
authors: L
authors: Kota
authors: Anil
authors: A
authors: Shinde
authors: Rajesh
authors: R
authors: Badange
authors: Pradeep
authors: P
authors: Jayarajan
authors: Gopinadh
authors: G
authors: Bhyrapuneni
authors: P K
authors: PK
authors: Dubey
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy; D004195:Disease Models, Animal; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008024:Ligands; D008297:Male; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014363:Tryptamines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D007211:Indoles; D008024:Ligands; D011985:Receptors, Serotonin; D013449:Sulfonamides; D014363:Tryptamines; C097216:serotonin 6 receptor