title: Conformationally restricted homotryptamines. Part 4: Heterocyclic and naphthyl analogs of a potent selective serotonin reuptake inhibitor.
abstract: A series of hybrid molecules containing the cyclopropylmethylamino side chain found in homotryptamine (1S,2S)-2c and an isosteric heteroaryl or naphthyl core were prepared and their binding affinities for the human serotonin transporter determined. The most potent isosteres were CN-substituted naphthalenes. These results demonstrate that isosteric aromatic cores which lack an H-bond donor site may be substituted for the indole nucleus without substantial loss in hSERT binding.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-7660, USA. dalton.king@bms.com
authors.forename: H
authors.initials: H
authors.lastname: Dalton King
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Denhart
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Deskus
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Ditta
authors.forename: James R
authors.initials: JR
authors.lastname: Epperson
authors.forename: Mendi A
authors.initials: MA
authors.lastname: Higgins
authors.forename: Joyce E
authors.initials: JE
authors.lastname: Kung
authors.forename: Lawrence R
authors.initials: LR
authors.lastname: Marcin
authors.forename: Charles P
authors.initials: CP
authors.lastname: Sloan
authors.forename: Gail K
authors.initials: GK
authors.lastname: Mattson
authors.forename: Thaddeus F
authors.initials: TF
authors.lastname: Molski
authors.forename: Rudolph G
authors.initials: RG
authors.lastname: Krause
authors.forename: Robert L
authors.initials: RL
authors.lastname: Bertekap
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Lodge
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Mattson
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
mesh_terms: D050483:Dopamine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D008968:Molecular Conformation; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014363:Tryptamines / Q000737:chemistry*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D006571:Heterocyclic Compounds; D050484:Norepinephrine Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014363:Tryptamines; C030820:tryptamine