title: Synthesis and evaluation of arylpiperazines derivatives of 3,5-dioxo-(2H,4H)-1,2,4-triazine as 5-HT1AR ligands.
abstract: 5-HT1AR agonist or partial agonists are established drug candidates for psychiatric and neurological disorders. We have reported the synthesis and evaluation of a series of high affinity 5-HT1AR partial agonist PET imaging agents with greater selectivity over α-1AR. The characteristic of these molecules are 3,5-dioxo-(2H,4H)-1,2,4-triazine skeleton tethered to an arylpiperazine unit through an alkyl side chain. The most potent 5-HT1AR agonistic properties were found to be associated with the molecules bearing C-4 alkyl group as the linker. Therefore development of 3,5-dioxo-(2H,4H)-1,2,4-triazine bearing arylpiperazine derivatives may provide high affinity selective 5-HT1AR ligands. Herein we describe the synthesis and evaluation of the binding properties of a series of arylpiperazine analogues of 3,5-dioxo-(2H,4H)-1,2,4-triazine.
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, USA; Department of Psychiatry and Behavior Science, Stony Brook University, New York, USA. Electronic address: kumardi@nyspi.columbia.edu.
authors.forename: J S Dileep
authors.initials: JSD
authors.lastname: Kumar
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, USA.
authors.forename: Vattoly J
authors.initials: VJ
authors.lastname: Majo
authors.affiliation: Columbia University College of Physicians and Surgeons, New York, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.affiliation: Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, USA; Columbia University College of Physicians and Surgeons, New York, USA.
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D008024:Ligands; D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; D014227:Triazines; D044282:Receptor, Serotonin, 5-HT1A
keywords: 5-HT; 5-HT(1A)R; Agonist; Arylpiperazine; α-1AR