Lipophilicity and serotonin agonist activity in a series of 4-substituted mescaline analogs

Abstract

Replacement of the 4-methoxy of mescaline with higher alkyl homologues or with Br 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 5 atoms in length. 3,4,5-Trisubstitution may give compounds which are as active as those with the 2,4,-5-substitution pattern.