D. Trachsel
Jul 1, 2003
Citations
1
Influential Citations
7
Citations
Journal
Helvetica Chimica Acta
Abstract
Synthesis of Novel (Phenylalkyl)amines for the Investigation of Structure–Activity Relationships. Part 21). 4-Thio-Substituted [2-(2,5-Dimethoxyphenyl)ethyl]amines (=2,5-Dimethoxybenzeneethanamines) The 4-substituted [2-(2,5-dimethoxyphenyl)ethyl]amines (=2,5-dimethoxybenzeneethanamines) and its α-methyl analogs are known to act as potent 5-HT2A/C ligands, which have, depending on their 4-substituent, agonistic or antagonistic character. Generally, compounds with a small lipophilic substituent typically are agonists and those with a larger lipophilic substituent predominantly antagonists or at least partial agonists. Since little is known about the transition and more information is needed about the structural requirements of the 4-substituent to control the functional activity, 12 novel 4-thio-substituted [2-(2,5-dimethoxyphenyl)ethyl]amines were synthesized and spectroscopically characterized. Thus 2,5-dimethoxybenzenethiol (7) was converted to the thioether derivatives 8a–l with several alkyl, fluoroalkyl, alkenyl, and benzyl halides. Subsequent Vilsmeier-formylation afforded the benzaldehydes 9a–l, condensation with MeNO2 the nitroethenyl derivatives 10a–l, and reduction with AlH3 the desired (2-phenylethyl)amines 11a–l.