3213-28-3Relevant articles and documents
Synthesis and Functional Characterization of 2-(2,5-Dimethoxyphenyl)-N-(2-fluorobenzyl)ethanamine (25H-NBF) Positional Isomers
Pottie, Eline,Kupriyanova, Olga V.,Shevyrin, Vadim A.,Stove, Christophe P.
, p. 1667 - 1673 (2021/05/31)
Serotonergic psychedelics, substances exerting their pharmacological action through activation of the serotonin 2A receptor (5-HT2AR), have continuously comprised a substantial fraction of the over 1000 reported New Psychoactive Substances (NPS) so far. Within this category, N-benzyl derived phenethylamines, such as NBOMes and NBFs, have shown to be of particular relevance. As these substances remain incompletely characterized, this study aimed at synthesizing positional isomers of 25H-NBF, with two methoxy groups placed on different positions of the phenyl group of the phenethylamine moiety. These isomers were then functionally characterized in an in vitro bioassay monitoring the recruitment of β-Arrestin 2 to the 5-HT2AR through luminescent readout via the NanoBiT technology. The obtained results provide insight into the optimal substitution pattern of the phenyl group of the phenethylamine moiety of N-benzyl derived substances, a feature so far mostly explored in the phenethylamines underived at the N-position. In the employed bioassay, the most potent substances were 24H-NBF (EC50 value of 158 nM), 26H-NBF (397 nM), and 25H-NBF (448 nM), with 23H-NBF, 35H-NBF, and 34H-NBF yielding μM EC50 values. A similar ranking was obtained for the compounds' efficacy: Taking as a reference LSD (lysergic acid diethylamide), 24H-, 26H-, and 25H-NBF had an efficacy of 106-107%, followed by 23H-NBF (96.1%), 34H-NBF (75.2%), and 35H-NBF (58.9%). The stronger activity of 24H-, 25H-, and 26H-NBF emphasizes the important role of the methoxy group at position 2 of the phenethylamine moiety for the in vitro functionality of NBF substances.
Biomimetic Phosphate-Catalyzed Pictet-Spengler Reaction for the Synthesis of 1,1′-Disubstituted and Spiro-Tetrahydroisoquinoline Alkaloids
Zhao, Jianxiong,Méndez-Sánchez, Daniel,Ward, John M.,Hailes, Helen C.
, p. 7702 - 7710 (2019/06/17)
Tetrahydroisoquinoline (THIQ) alkaloids are an important group of compounds that exhibit a range of bioactivities. Here, a phosphate buffer-catalyzed Pictet-Spengler reaction (PSR) using unreactive ketone substrates is described. A variety of 1,1′-disubst
Synthesis of 3-Benzazepines by Metal-Free Oxidative C–H Bond Functionalization–Ring Expansion Tandem Reaction
Gini, Andrea,Bamberger, Julia,Luis-Barrera, Javier,Zurro, Mercedes,Mas-Ballesté, Rubén,Alemán, José,Manche?o, Olga García
supporting information, p. 4049 - 4056 (2016/12/30)
A metal-free synthesis of biologically important benzazepines is achieved through a single synthetic operation involving an oxidative C–H bond functionalization and ring expansion with diazomethanes as key reagent. This represents a new, strong methodology for the straightforward construction of the seven-ring N-heterocyclic structures under mild conditions using a 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) oxoammonium salt as oxidant. Moderate to good yields are achieved from simple, readily available tetrahydroisoquinolines, and this methodology has been further successfully applied for the synthesis of the 3-benzazepine drug Lorcaserin. A possible mechanistic pathway for the ring expansion step, comprising the extrusion of nitrogen in a concerted asynchronic process, is proposed based on both mechanistic proof and density function theory (DFT) calculations. (Figure presented.).
