title: Conformationally restricted homotryptamines 3. Indole tetrahydropyridines and cyclohexenylamines as 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.
authors: Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-7660, USA. jeffrey.deskus@bms.com
authors: Jeffrey A
authors: JA
authors: Deskus
authors: James R
authors: JR
authors: Epperson
authors: Charles P
authors: CP
authors: Sloan
authors: Joseph A
authors: JA
authors: Cipollina
authors: Pierre
authors: P
authors: Dextraze
authors: Jingfang
authors: J
authors: Qian-Cutrone
authors: Qi
authors: Q
authors: Gao
authors: Baoqing
authors: B
authors: Ma
authors: Brett R
authors: BR
authors: Beno
authors: Gail K
authors: GK
authors: Mattson
authors: Thaddeus F
authors: TF
authors: Molski
authors: Rudolph G
authors: RG
authors: Krause
authors: Matthew T
authors: MT
authors: Taber
authors: Nicholas J
authors: NJ
authors: Lodge
authors: Ronald J
authors: RJ
authors: Mattson
mesh_terms: D000818:Animals; D053138:Cyclohexenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005473:Fluoxetine / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017551:Microdialysis; D008968:Molecular Conformation; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D014363:Tryptamines / Q000737:chemistry*
chemical_list: D053138:Cyclohexenes; D005473:Fluoxetine; D007211:Indoles; D011725:Pyridines; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014363:Tryptamines; C493230:SLC6A4 protein, human