Rd. Clark et al., SYNTHESIS AND PRELIMINARY PHARMACOLOGICAL EVALUATION OF 2-BENZYLOXY SUBSTITUTED ARYL KETONES AS 5-HT4 RECEPTOR ANTAGONISTS, Bioorganic & medicinal chemistry letters, 4(20), 1994, pp. 2481-2484
Structural modification of the 2-methoxy group and at the 4-position o
f the piperidine ring of the 5-HT4 partial agonist 1 led to analogues
with increased affinity for the 5-HT4 receptor and loss of agonist act
ivity. Similar modification of 2 resulted in 2-(3,5-dimethoxy)benzylox
y derivatives (23,24,26-28) that were found to be 5-HT4 receptor antag
onists with subnanomolar affinity.