Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogs
Journal of Medicinal Chemistry – February 01, 1977
Source: OpenAlex
Summary
Replacing the 4-methoxy group in mescaline with higher alkyl homologues or bromine significantly enhanced activity at serotonin receptors, as demonstrated in a sheep umbilical artery preparation. This increase in receptor activity was linked to lipophilicity, with 1-octanol-water partition coefficients revealing optimal effects for shorter chain lengths. Notably, when the 4-substituent exceeded five atoms, receptor activity declined. These findings underscore the importance of stereochemistry and pharmacological properties in developing effective serotonin agonists, potentially influencing future pharmaceutical applications.
Abstract
Replacement of the 4-methoxy of mescaline with higher alkyl homologues or with bromine led to increased activity at serotonin receptors in a sheep umbilical artery preparation. This activity appears correlated with lipophilicity, as measured by 1-octanol-water partition coefficients, but drops off when the 4-substituent is about five atoms in length. It is suggested that 3,4,5-trisubhe 2,4,5-substitution pattern.