Synthesis and Biological Evaluation of Novel Compounds within a Class of 3-Aminochroman Derivatives with Dual 5-HT1A Receptor and Serotonin Transporter Affinity

• Published in: Journal of medicinal chemistry Vol. 49; no. 15; pp. 4785 - 4789
• Main Authors: Hatzenbuhler, Nicole T, Evrard, Deborah A, Harrison, Boyd L, Huryn, Donna, Inghrim, Jennifer, Kraml, Christina, Mattes, James F, Mewshaw, Richard E, Zhou, Dahui, Hornby, Geoffrey, Lin, Qian, Smith, Deborah L, Sullivan, Kelly M, Schechter, Lee E, Beyer, Chad E, Andree, Terrance H
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 27.07.2006; Amer Chemical Soc
• Subjects: Animals; Antidepressive Agents - chemical synthesis; Antidepressive Agents - chemistry; Antidepressive Agents - pharmacology; Benzopyrans - chemical synthesis; Benzopyrans - chemistry; Benzopyrans - pharmacology; Biological and medical sciences; Chemistry, Medicinal; CHO Cells; Chromans - chemical synthesis; Chromans - chemistry; Chromans - pharmacology; Cricetinae; Cricetulus; Frontal Lobe - drug effects; Frontal Lobe - metabolism; Humans; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Life Sciences & Biomedicine; Medical sciences; Microdialysis; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Radioligand Assay; Rats; Science & Technology; Serotonin - biosynthesis; Serotonin 5-HT1 Receptor Agonists; Serotonin 5-HT1 Receptor Antagonists; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin Uptake Inhibitors - chemical synthesis; Serotonin Uptake Inhibitors - chemistry; Serotonin Uptake Inhibitors - pharmacology; Serotoninergic system; Stereoisomerism; Structure-Activity Relationship; ANTIDEPRESSANTS; RAT FRONTAL-CORTEX; IN-VIVO; DRUGS; PINDOLOL; ANTAGONISTS; BINDING; NEXT-GENERATION; BRAIN; UPTAKE INHIBITORS; Rat; Serotonin; Rodentia; Oxygen heterocycle; In vitro; Biological activity; Chroman derivatives; In vivo; Vertebrata; Mammalia; 5-HT1A Serotonine receptor; Membrane transport; Animal; Neurotransmitter; Affinity; Chemical synthesis; Carrier protein
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm060218h

Compounds containing a 5-carbamoyl-8-fluoro-3-amino-3,4-dihydro-2H-1-benzopyran and a 3-alkylindole moiety linked through a common basic nitrogen were prepared and evaluated for 5-HT1A affinity, serotonin rat transporter affinity, and functional antagonist activity in vitro. 26a was found to be the most potent and selective compound in this series and was shown to possess neurochemical activity in vivo by producing acute and rapid increases in 5-HT in the rat frontal cortex.