Multistep solution-phase parallel synthesis of spiperone analogues.
A flexible, multistep parallel synthesis of spiperone analogues is described. A library of 4-substituted piperidines, assembled utilizing reductive amination and acylation protocols, was alkylated either homogeneously or heterogeneously, exploiting a product release only concept, to afford an oxa-series of spiperone analogues. Screening of the products at 5-HT2 and D2 receptors revealed 5-HT2A antagonists with improved selectivity compared to spiperone and AMI-193.
Hansen
H C
HC
Synthetic Chemistry, ACADIA Pharmaceuticals A/S, Glostrup, Denmark.
Olsson
R
R
Croston
G
G
Andersson
C M
CM
D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001372:Aza Compounds / Q000494:pharmacology; D001681:Biological Assay; D002460:Cell Line; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011985:Receptors, Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013134:Spiperone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology
D014150:Antipsychotic Agents; D001372:Aza Compounds; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013141:Spiro Compounds; C003338:spiramide; D013134:Spiperone