Synthesis and structure-activity relationship of novel conformationally restricted analogues of serotonin as 5-HT6 receptor ligands
| Autor: | Ramasastri Kambhampati, Pramod Kumar Dubey, Amol D. Deshpande, Parandhama Gudla, Sobhanadri Arepalli, Prabhakar Kothmirkar, Narasimhareddy P Gangadasari, Adireddy Dwarampudi, Anil Kashinath Chindhe, Ramakrishna Nirogi, Thrinath Reddy Bandyala, Jagadishbabu Konda, Shinde Anil Karbhari |
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| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
Serotonin Dose-Response Relationship Drug Chemistry Stereochemistry Molecular Conformation General Medicine Water maze Ligands Tryptamines chemistry.chemical_compound Structure-Activity Relationship Drug Design Receptors Serotonin Drug Discovery 5-HT6 receptor Structure–activity relationship Humans Receptor Lead compound ADME |
| Zdroj: | Journal of enzyme inhibition and medicinal chemistry. 27(3) |
| ISSN: | 1475-6374 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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