Phenylalkylamines with potential psychotherapeutic utility. 2. Nuclear substituted 2-amino-1-phenylbutanes

Abstract

A series of 2-amino-1-(4-substituted-2,5-dimethoxyphenyl)butanes (Table V) was prepared as analogues of (R)-2-amino-1-(2,5-dimethoxy-4-methylphenyl)butane (1a). 1-(2,5-Dimethoxyphenyl)-2-(N-phthalimido)butane (7) was utilized as a synthetic intermediate common to many of the target compounds. Animal data are presented indicating that most of these analogues have low hallucinogenic potential. Selected compounds were compared with 1a in an avoidance-response acquisition model which differentiates between 1a and the human hallucinogens DOM (2a) and DOET (2b). Structure-activity relationships of these analogues are discussed.

Structure-Activity Relationships of Phenethylamine Hallucinogens

“…This result was observed in 3,4,5-trimethoxy compounds and in several 2,5-dimethoxy-4-substituted analogs (77). This result was observed in 3,4,5-trimethoxy compounds and in several 2,5-dimethoxy-4-substituted analogs (77).…”

1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT2APartial Agonists

“…Acylations of this type have been shown to occurs exclusively at the 4-position. 12 Catalytic reduction of the ketone and subsequent deprotection afforded compounds 4-6. Compounds 7 and 8 were prepared in a somewhat different manner (Scheme 1).…”

“…Calcd. for (C21H30ClNO3) C, H, N.(()1-[2-Methoxy-4-(3-phenylpropyl)phenyl]-2-aminopropane HCl(12). Compound 12 was prepared from 49 in the same manner as 18.…”

Synthesis of deuterium labeled phenethylamine derivatives

“…To a solution of 2 (3.50 g, 25.0 mmol) in dry dichloromethane (478 ml) cooled in an ice bath was added titanium chloride (5.0 ml, 46.0 mmol), and dichloromethyl methyl ether (C1 2 CHOCH 3 ) (4.2 ml, 46.5 mmol) under an argon atmosphere. [20][21][22][23][24][25] The dark red reaction solution was stirred at room temperature for 15 min until the starting material was completely consumed as monitored by thin layer chromatography (TLC). The reaction was quenched by adding water (185 ml), and the dichloromethane layer was washed with water (140 ml) and then dried over anhydrous magnesium sulfate.…”