From the selective serotonin transporter inhibitor citalopram to the selective norepinephrine transporter inhibitor talopram: synthesis and structure-activity relationship studies.
Citalopram and talopram are structurally closely related, but they have very distinct pharmacological profiles as selective inhibitors of the serotonin and norepinephrine transporters, respectively. A systematic structure-activity relationship study was performed, in which each of the four positions distinguishing the two compounds were varied. The inhibitory potencies of the resulting 16 compounds were tested at both serotonin and norepinephrine transporters. This showed that particularly two of the four positions are determinants for the biological activity.
Eildal
Jonas N N
JN
Department of Medicinal Chemistry, The Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark.
Andersen
Jacob
J
Kristensen
Anders S
AS
Jørgensen
Anne Marie
AM
Bang-Andersen
Benny
B
Jørgensen
Morten
M
Strømgaard
Kristian
K
D000818:Animals; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002460:Cell Line; D015283:Citalopram / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D011437:Propylamines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
D001572:Benzofurans; D015283:Citalopram; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011437:Propylamines; D011994:Recombinant Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C496684:talopram