Synthesis and structure-activity relationship of novel conformationally restricted analogues of serotonin as 5-HT6 receptor ligands |
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Authors: | Nirogi Ramakrishna V S Kambhampati Ramasastri Kothmirkar Prabhakar Konda Jagadishbabu Bandyala Thrinath Reddy Gudla Parandhama Arepalli Sobhanadri Gangadasari Narasimhareddy P Shinde Anil K Deshpande Amol D Dwarampudi Adireddy Chindhe Anil K Dubey Pramod Kumar |
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Institution: | Discovery Research-Medicinal Chemistry, Suven Life Sciences Ltd., Banjara Hills, Hyderabad, India. ramakrishna_nirogi@yahoo.co.in |
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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. |
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