Kim, Juhyeon; Kim, Yoon Jung; Londhe, Ashwini M.; Pae, Ae Nim; Choo, Hyunah; Kim, Hak Joong; Min, Sun-Joon published the artcile< Synthesis and biological evaluation of disubstituted pyrimidines as selective 5-HT2C agonists>, SDS of cas: 374930-88-8, the main research area is pyrimidine preparation antagonist HT receptor; 5-HT2C receptor; binding affinity; cell-based assay; disubstituted pyrimidine; selectivity.
The synthesis of disubstituted pyrimidine derivatives I [R1 = 3-F, 4-F; n = 0, 1, 2; R2 = piperazin-1-yl, (2R)-2-methylpiperazin-1-yl, 1,4-diazepan-1-yl], II [R3 = (2R)-2-(3-fluorophenyl)propyl, (2R)-2-(4-fluorophenyl)propyl, 3-fluorophenyl, 4-fluorophenyl; R4 = 1,4-diazepan-1-yl, [(3R)-pyrrolidin-3-yl]aminyl, 2,7-diazaspiro[4.4]nonan-2-yl, etc.] and their biol. evaluation as selective 5-HT2C agonists were described. To improve selectivity for 5-HT2C over other subtypes, two series of disubstituted pyrimidines with fluorophenylalkoxy groups at either the 5-position or 4-position and varying cyclic amines at the 2-position were synthesized. The in vitro cell-based assay and binding assay identified compounds II [R3 = (2R)-2-(3-fluorophenyl)propyl, R4 = 1,4-diazepan-1-yl (I); R3 = (2R)-2-(4-fluorophenyl)propyl, R4 = 1,4-diazepan-1-yl] as potent 5-HT2C agonists. Further studies on selectivity to 5-HT subtypes and drug-like properties indicated that 2,4-disubstituted pyrimidine (I) showed a highly agonistic effect on the 5-HT2C receptor, with excellent selectivity, as well as exceptional drug-like properties, including high plasma and microsomal stability, along with low CYP inhibition. Thus, pyrimidine (I) could be considered a viable lead compound as a 5-HT2C selective agonist.
Moleculespublished new progress about 5-HT receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 374930-88-8 belongs to class piperazines, and the molecular formula is C13H19BrN4O2, SDS of cas: 374930-88-8.
Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics