Design and synthesis of dual 5-HT1A and 5-HT7 receptor ligands |
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| Institution: | 1. Division of Basic Pharmaceutical Sciences, Florida A&M University, College of Pharmacy and Pharmaceutical Sciences, Tallahassee, FL 32307, USA;2. Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA;3. National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7365, USA;4. Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7360, USA;1. Centre for Ionics University of Malaya, Department of Physics, Faculty of Science, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia;2. Department of Chemistry, Sciences & Arts College – Rabigh, King Abdulaziz University, Rabigh, Saudi Arabia;3. Department of Chemistry, Faculty of Science, University of Malaya, Lembah Pantai, 50603 Kuala Lumpur, Malaysia;1. Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia;2. Center of Excellence for Advanced Materials Research (CEAMR), King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia;1. Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland;2. Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland;3. Institute of Pharmacology, Polish Academy of Sciences, 12 Sm?tna Street, 31-343 Kraków, Poland;1. Dipartimento di Farmacia Università di Napoli “Federico II”, Via D. Montesano, 49, 80131, Naples, Italy;2. Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze Università di Siena, Via delle Scotte, 6, 53100, Siena, Italy;3. Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 20-093 Lublin, Poland;4. Department of Biochemistry, Medical University of Warsaw, 02-097 Warszawa, Poland;1. Department of Clinical Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland;2. Institute of Pharmacology, Polish Academy of Sciences, Department of Medicinal Chemistry, 12 Sm?tna Street, 31-343 Krakow, Poland;3. Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland;4. Department of Organic Chemistry, Medical University of Silesia, 4 Jagiellońska Street, 41-200 Sosnowiec, Poland |
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| Abstract: | 5-HT1A and 5-HT7 receptors have been at the center of discussions recently due in part to their major role in the etiology of major central nervous system diseases such as depression, sleep disorders, and schizophrenia. As part of our search to identify dual targeting ligands for these receptors, we have carried out a systematic modification of a selective 5HT7 receptor ligand culminating in the identification of several dual 5-HT1A and 5-HT7 receptor ligands. Compound 16, a butyrophenone derivative of tetrahydroisoquinoline (THIQ), was identified as the most potent agent with low nanomolar binding affinities to both receptors. Interestingly, compound 16 also displayed moderate affinity to other clinically relevant dopamine receptors. Thus, it is anticipated that compound 16 may serve as a lead for further exploitation in our quest to identify new ligands with the potential to treat diseases of CNS origin. |
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| Keywords: | Dual receptor ligands Multi-receptor targeting CNS ligands Serotonin receptors |
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