Rigidized 1-aryl sulfonyl tryptamines: synthesis and pharmacological evaluation as 5-HT6 receptor ligands |
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| Authors: | Nirogi Ramakrishna Dwarampudi Adireddy Kambhampati Ramasastry Bhatta Venugopalarao Kota Laxman Shinde Anil Badange Rajesh Jayarajan Pradeep Bhyrapuneni Gopinadh Dubey P K |
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| Institution: | a Discovery Research, Suven Life Sciences Ltd., Serene Chambers, Road-5, Avenue-7, Banjara Hills, Hyderabad 500 034, India
b Department of Chemistry, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500 085, India |
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| Abstract: | A series of N1-arylsulfonyl-3-(pyrrolidin-3-yl)-1H-indole and N1-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-HT6 receptor. Several compounds displayed potent binding affinity for the 5-HT6 receptor when tested in in vitro binding assay. The primary SAR indicates that rigidification of dimethylamino alkyl chain at C3 of indole carbon maintains the binding affinity to 5-HT6R. The lead compound N1-benzenesulfonyl-3-(4-chloro-1-methyl-2,5-dihydro-1H-pyrrol-3-yl)-1H-indole, 10a (Kb = 0.1 nM) has shown excellent in vitro affinity and was active in animal models of cognition like NORT and water maze. |
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| Keywords: | 5-HT6R antagonist SAR NORT Water maze |
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