122nd General Meeting of the KCS

Type Poster Presentation
Area Medicinal Chemistry
Room No. Grand Ballroom
Time 10월 18일 (목요일) 11:00~12:30
Code MEDI.P-299
Subject Synthesis and biological evaluation of pyrimidine derivatives as selective 5-HT2C ligands
Authors Kim Yoonjung, Sun-Joon Min1,*
Department of Applied Chemistry, Hanyang University, Korea
1Dept of Chemical & Molecular Eng/Applied Chemistry, Hanyang University, Korea
Abstract Serotonin (5-HT) is one of the major neurotransmitters that is primarily located in the central nerve system (CNS) and plays an important role in the regulation of a variety of physiological functions such as intestinal movements, mood, cognition, appetite and psychiatric diseases. 5-HT receptors, e.g., 5-HT1A, 5-HT2A, and 5-HT2C subtypes, may also play a role in cognitive and motivational disabilities in psychoses and mood disorders. For example, several antipsychotic and antidepressant drugs have been suggested to ameliorate negative symptoms and mood disturbances, partly through actions on 5-HT1A and 5-HT2A receptors. Clozapine, a prototype of atypical antipsychotic drugs, which is most effective in treating negative symptoms of schizophrenia, may act as an inverse agonist on 5-HT2C receptors. It has been studied that neurotransmitters such as dopamine (DA) and 5HT are directly/indirectly associated with psychiatric disorders. More recently, interest has emerged in the therapeutic potential of compounds with agonistic activities at 5-HT2C receptors to address unmet medical needs across the symptom domains of schizophrenia. Although several compounds have been identified as 5HT2C agonists, new compounds with high selectivity against other 5-HT subtypes are still requested for clinical development. Herein, we describes synthesis and evaluation of pyrimidine derivatives as selective 5-HT2C ligands. We have identified several compounds showing high binding affinity toward 5-HT2C receptors. We also found that those pyrimidine analogues displayed excellent agonistic activity in cell-based functional assay. Further evaluation of these compounds regarding selectivity and stability will be addressed in this presentation.
E-mail moli24520@gmail.com