1. Conformationally restricted homotryptamines 3. Indole tetrahydropyridines and cyclohexenylamines as selective serotonin reuptake inhibitors
- Author
-
Rudolph G. Krause, Charles P. Sloan, Jingfang Qian-Cutrone, Thaddeus F. Molski, Joseph A. Cipollina, Gail K. Mattson, Matthew T. Taber, Qi Gao, Ronald J. Mattson, Jeffrey A. Deskus, James R. Epperson, Brett R. Beno, Baoqing Ma, Nicholas J. Lodge, and Pierre Dextraze
- Subjects
Indoles ,Nitrile ,Pyridines ,Stereochemistry ,Microdialysis ,Clinical Biochemistry ,Molecular Conformation ,Substituent ,Pharmaceutical Science ,Biochemistry ,chemistry.chemical_compound ,Fluoxetine ,Cyclohexenes ,Drug Discovery ,Animals ,Humans ,Serotonin Uptake Inhibitors ,Molecular Biology ,Serotonin transporter ,Serotonin Plasma Membrane Transport Proteins ,Indole test ,biology ,Organic Chemistry ,Tryptamines ,Rats ,chemistry ,biology.protein ,Molecular Medicine ,Serotonin ,Reuptake inhibitor ,Selective Serotonin Reuptake Inhibitors - Abstract
A series of indole tetrahydropyridine and indole cyclohexenylamines was prepared, and their binding affinities at the human serotonin transporter (SERT) were determined. In particular, a nitrile substituent at the C5 position of the indole ring gave potent SERT activity. The stereochemistry of the N,N-dimethylamine substituent was determined for the most potent indole cyclohexenylamine, 6a. The enantiomers of 6a were energy minimized and compared to other conformationally restricted SSRIs. Compound 6a was found to give a dose-response similar to the SSRI fluoxetine in microdialysis studies in rats.
- Published
- 2007
- Full Text
- View/download PDF