Parallel synthesis of 3-aryloxy-2-propanolamines and evaluation as dual affinity 5-HT(1A) and 5-HT re-uptake ligands.
A solution phase synthesis for the preparation of 3-aryloxy-2-propanolamine libraries has been developed. This resulted in the identification of 5 as a ligand with dual affinity for 5-HT1A and serotonin reuptake receptors which shows excellent pharmacokinetic parameters.
van Niel
M B
MB
Department of Chemistry, Merck, Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, United Kingdom. Monique_vanniel@merck.com
Beer
M S
MS
Castro
J L
JL
Cheng
S K
SK
Evans
D C
DC
Heald
A
A
Hitzel
L
L
Hunt
P
P
Mortishire-Smith
R
R
O'Connor
D
D
Watt
A P
AP
MacLeod
A M
AM
D008024:Ligands; D011412:Propanolamines / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics
D008024:Ligands; D011412:Propanolamines; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors