138371-65-0Relevant articles and documents
Synthetic Cathinone Analogues Structurally Related to the Central Stimulant Methylphenidate as Dopamine Reuptake Inhibitors
Yadav-Samudrala, Barkha J.,Eltit, Jose M.,Glennon, Richard A.
, p. 4043 - 4050 (2019)
Synthetic cathinones are, primarily, stimulant drugs of abuse that act at monoamine transporters (e.g., the dopamine transporter or DAT) as releasing agents or as reuptake inhibitors. In the past few years, the emergence of >150 new synthetic cathinones has attracted considerable attention from medical and law enforcement communities. threo-Methylphenidate (tMP), used clinically for the treatment of ADHD and narcolepsy, is also a DAT reuptake inhibitor. tMP is somewhat structurally similar to abused cathinone stimulants, and the structure-activity relationships (SAR) of tMP have been well-defined. Hence, available tMP literature might assist in understanding the SAR of synthetic cathinones, about which less is known. In the present study, we synthesized and examined eight 2-benzoylpiperidine analogues (4, 6-12) to determine if tMP SAR might be applicable to cathinone SAR. The benzoylpiperidine analogues were evaluated in a competition assay using live-cell imaging against APP+ in HEK293 cells stably expressing hDAT and in cells coexpressing DAT and voltage-gated Ca2+ channels. All compounds were found to be DAT reuptake inhibitors, and a significant correlation was obtained between the potency of the benzoylpiperidines and tMP binding data (r = 0.91), suggesting that the SAR of tMP analogues might be directly applicable to certain synthetic cathinones as DAT reuptake inhibitors.
The conformational behaviour of 4,4a,5,6,7,8-hexahydropyrido[1,2-d] [1,3,4]oxadiazine derivatives studied by NMR spectroscopy and molecular mechanics
Rosling, Ari,Hotokka, Matti,Klika, Karel D.,Fueloep, Ferenc,Sillanpaeae, Reijo,Mattinen, Jorma
, p. 213 - 221 (2007/10/03)
The diastereomers (1'R*,2R*)- and (1'S*,2R*)-1-amino-2-(1'-hydroxypiperidinebenzyl) and 1-amino-2-(1-hydroxy-1,1-diphenylmethyl) piperidine have been synthesized and transformed into the corresponding 4,4a,5,6,7,8-hexahydropyrido[1,2d][1,3,4]oxadiazines. Similarly to the unsubstituted parent compound 2-phenylhexahydropyrido[1,2d][1,3,4]oxadiazine, both the (4R*,4aR*)- and the (4S*,4aR*)-2,4-diphenylhexahydropyrido[1,2-d][1,3,4]oxadiazines were found to be predominantly in the trans-annellated conformation. This was concluded from low temperature NMR measurements, the chemical shift differences of the methylene protons adjacent to the bridged nitrogen, or the ΔH° values derived from ab initio calculations. In 2,4,4-triphenylhexahydropyrido[1,2-d][1,3,4]oxadiazine the conformational preference was switched to a slight predominance of the cis N-in conformation (53%). The conformational preference in the solid state for the (4R*,4aR*)- and the (4S*,4aR*)-2,4-diphenylhexahydropyrido[1,2-d][1,3,4]oxadiazines was the same as in solution. The 15N chemical shifts of the bridgehead nitrogens were found to correlate to some extent with the conformational preference, while no correlation was observed between the geminal coupling constant of the methylene protons adjacent to the bridgehead and the adopted ring annellation.
