24920-40-9Relevant academic research and scientific papers
Sulfur-substituted α-alkyl phenethylamines as selective and reversible MAO-A inhibitors: Biological activities, CoMFA analysis, and active site modeling
Gallardo-Godoy, Alejandra,Fierro, Angélica,McLean, Thomas H.,Castillo, Mariano,Cassels, Bruce K.,Reyes-Parada, Miguel,Nichols, David E.
, p. 2407 - 2419 (2007/10/03)
A series of phenethylamine derivatives with various ring substituents and with or without N-methyl and/or C-α methyl or ethyl groups was synthesized and assayed for their ability reversibly to inhibit monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). Several compounds showed potent and selective MAO-A inhibitory activity (IC50 in the submicromolar range) but none showed appreciable activity toward MAO-B. A three-dimensional quantitative structure-activity relationship study for MAO-A inhibition was performed on the series using comparative molecular field analysis (CoMFA). The resulting model gave a cross-validated q2 of 0.72 and showed that in this series of compounds steric properties of the substituents were more important than electrostatic effects. Molecular modeling based on the recently published crystal structure of inhibitor-bound MAO-A provided detailed evidence for specific interactions of the ligands with the enzyme, supported by previous references and consistent with results from the CoMFA. On the basis of these results, structural determinants for selectivity of substituted amphetamines for MAO-A are discussed.
Synthesis of novel (phenylalkyl)amines for the investigation of structure-activity relationships. Part 2. 4-Thio-substituted [2-(2,5-dimethoxyphenyl)ethyl]amines (=2,5-dimethoxybenzeneethanamines)
Trachsel, Daniel
, p. 2610 - 2619 (2007/10/03)
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-I with several alkyl, fluoroalkyl, alkenyl, and benzyl halides. Subsequent Vilsmeier-formylation afforded the benzaldehydes 9a-I, condensation with MeNO2 the nitroethenyl derivatives 10a-I, and reduction with AIH3 the desired (2-phenylethyl)amines 11a-I.
