title: Solid-Supported Synthesis and 5-HT7 /5-HT1A Receptor Affinity of Arylpiperazinylbutyl Derivatives of 4,5-dihydro-1,2,4-triazine-6-(1H)-one.
abstract: A series of arylpiperazinylbutyl derivatives of 4,5-dihydro-1,2,4-triazine-6(1H)-ones was designed and synthesized according to the new solid-supported methodology. In this approach, triazinone scaffold was constructed from the Fmoc-protected glycine. The library representatives showed different levels of affinity for 5-HT7 and 5-HT1A receptors; compounds 13, 14 and 18-20 were classified as dual 5-HT7 /5-HT1A receptors ligands. The structure-affinity relationship analysis revealed that the receptor affinity and selectivity of the tested compounds depended on the kind of substituent in position 3 of triazinone fragment as well as substitution pattern of the phenylpiperazine moiety.
authors: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Kraków, Poland.
authors: Katarzyna
authors: K
authors: Grychowska
authors: Department of Aminoacids, Peptides and Proteins Institute of Biomolecules Max Mousseron, UMR CNRS 5247, 15 Charles Flahault Av., 34093, Montpellier, France.
authors: Nicolas
authors: N
authors: Masurier
authors: Department of Aminoacids, Peptides and Proteins Institute of Biomolecules Max Mousseron, UMR CNRS 5247, 15 Charles Flahault Av., 34093, Montpellier, France.
authors: Pascal
authors: P
authors: Verdié
authors: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors: Grzegorz
authors: G
authors: Satała
authors: Department of Medicinal Chemistry, Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna Street, 31-343, Kraków, Poland.
authors: Andrzej J
authors: AJ
authors: Bojarski
authors: Department of Aminoacids, Peptides and Proteins Institute of Biomolecules Max Mousseron, UMR CNRS 5247, 15 Charles Flahault Av., 34093, Montpellier, France.
authors: Jean
authors: J
authors: Martinez
authors: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Kraków, Poland.
authors: Maciej
authors: M
authors: Pawłowski
authors: Department of Aminoacids, Peptides and Proteins Institute of Biomolecules Max Mousseron, UMR CNRS 5247, 15 Charles Flahault Av., 34093, Montpellier, France.
authors: Gilles
authors: G
authors: Subra
authors: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Kraków, Poland.
authors: Paweł
authors: P
authors: Zajdel
mesh_terms: D008024:Ligands; D010879:Piperazines / Q000737:chemistry; D011869:Radioligand Assay / Q000379:methods; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D060327:Solid-Phase Synthesis Techniques; D013329:Structure-Activity Relationship; D014227:Triazines / Q000737:chemistry
chemical_list: D008024:Ligands; D010879:Piperazines; D011985:Receptors, Serotonin; D014227:Triazines; C104425:serotonin 7 receptor; D044282:Receptor, Serotonin, 5-HT1A; C031503:phenylpiperazine
keywords: 5-HT1ARs ligands; 5-HT7Rs ligands; long-chain arylpiperazines; solid-phase synthesis; triazinones