Centrally active N-substituted analogs of 3,4-methylenedioxyphenylisopropylamine (3,4-methylenedioxyamphetamine)

• Published in: Journal of pharmaceutical sciences 1980-02, Vol.69 (2), p.192-195
• Main Authors: Braun, Ulrich, Shulgin, Alexander T., Braun, Gisela
• Format: Article
• Language: English
• Subjects: 3,4-Methylenedioxyamphetamine - analogs & derivatives; 3,4-Methylenedioxyamphetamine - chemical synthesis; 3,4-Methylenedioxyamphetamine - pharmacology; 3,4-Methylenedioxyphenylisopropylamine—synthesis of centrally active N-substituted analogs; 4-Methylenedioxyphenylisopropylamine-synthesis of centrally active N-substituted analogs; Amines; Amines, phenylalkyl, substituted—N-substituted analogs of psychotomimetic agents; Amphetamines - chemical synthesis; Analgesics; Animals; Central Nervous System Agents - chemical synthesis; Central Nervous System Stimulants; Dogs; Guinea Pigs; Haplorhini; Humans; In Vitro Techniques; Lethal Dose 50; Mice; Motor Activity - drug effects; phenylalkyl; Psychotomimetic agents-N-substituted analogs of known centrally active agents; Rats; Reaction Time - drug effects; Species Specificity; substituted-N-substituted analogs of psychotomimetic agents
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600690220

The known central nervous system activity of 3,4-methylenedioxyphenylisopropylamine and its N-methyl homolog prompted the synthesis of a series of analogs with substituents on the nitrogen atom. Most of these analogs (R = alkyl, alkenyl, hydroxy, alkoxy, and alkoxyalkyl) were prepared by the reductive alkylation of 3,4-methylenedioxyphenylacetone with the appropriate amine and sodium cyanoborohydride. Hindered isomers were synthesized indirectly. Measurements of their pharmacological activity in several animal assays and in human subjects indicated that the central activity decreased with the increasing bulk of the N-substituent.