Phenylalkylamines with potential psychotherapeutic utility. 2. Nuclear substituted 2-amino-1-phenylbutanes
Robert T. Standridge, Henry G. Howell, Hugh A. Tilson, J. Chamberlain, Henry M. Holava, Jonas A. Gylys, R. A. Partyka, Alexander T. Shulgin
Journal of Medicinal Chemistry February 1, 1980 DOI: 10.1021/jm00176a010
Summary
Most of the synthesized 2-amino-1-(4-substituted-2,5-dimethoxyphenyl)butanes exhibited low hallucinogenic potential, highlighting their promise in plant-based medicinal research. In an evaluation involving 50 animal subjects, selected compounds were tested against (R)-2-amino-1-(2,5-dimethoxy-4-methylphenyl)butane, revealing significant differences from known hallucinogens DOM and DOET. The study employed a unique avoidance-response acquisition model to assess effects, contributing valuable insights into the structure–activity relationships of these analogues within the fields of chemistry, neuroscience, and neuropharmacology.
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.