Synthesis of some tropane derivatives of anticipated activity on the reuptake of norepinephrine and/or serotonin.
A variety of tropane derivatives 14a-g were prepared via the reaction of the alcohol analogs 12a and 12b with substituted fluorobenzenes 13a-f. The prepared compounds were tested for their activity and selectivity toward the norepinephrine transporter (NET) and serotonin transporter (SERT) using yohimbine-induced mortality and 5-hydroxytryptophan-induced neurotoxicity in mice, respectively. All the tested compounds were found to be NE and 5-HT reuptake inhibitors except 14d which exhibited selective 5-HT reuptake inhibition activity.
Hanna
Mona M
MM
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Eid
Nahed M
NM
George
Riham F
RF
Safwat
Hani M
HM
D006916:5-Hydroxytryptophan / Q000633:toxicity; D000317:Adrenergic alpha-Antagonists / Q000633:toxicity; D000818:Animals; D015283:Citalopram / Q000138:chemical synthesis / Q000737:chemistry; D002997:Clomipramine / Q000138:chemical synthesis / Q000737:chemistry; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005473:Fluoxetine / Q000138:chemical synthesis / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D009638:Norepinephrine / Q000494:pharmacology*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D014326:Tropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015016:Yohimbine / Q000037:antagonists & inhibitors / Q000633:toxicity
D006916:5-Hydroxytryptophan; D000317:Adrenergic alpha-Antagonists; D015283:Citalopram; D002997:Clomipramine; D005473:Fluoxetine; D009638:Norepinephrine; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014326:Tropanes; D015016:Yohimbine