title: Conformationally restricted homotryptamines. Part 6: indole-5-cycloalkyl methylamines as selective serotonin reuptake inhibitors.
abstract: Racemic 5-(trans-2-aminomethylcyclopropyl)indoles, 5-(trans-2-aminomethylcyclopentyl) indoles, and 5-(cis-2-aminomethylcyclopentyl)indoles were synthesized and evaluated as selective serotonin reuptake inhibitors. These analogs followed SAR trends similar to those previously reported for 3-cycloalkyl substituted indoles. The most potent analogs exhibited single digit nanomolar inhibition at the human serotonin transporter but were 10-fold less active than the previously reported compounds.
authors.affiliation: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492-7660, USA. jonathan.ditta@bms.com
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Ditta
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Denhart
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Deskus
authors.forename: James R
authors.initials: JR
authors.lastname: Epperson
authors.forename: Zhaoxing
authors.initials: Z
authors.lastname: Meng
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: Gail K
authors.initials: GK
authors.lastname: Mattson
authors.forename: Mellissa A
authors.initials: MA
authors.lastname: Lapaglia
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Taber
authors.forename: Thaddeus F
authors.initials: TF
authors.lastname: Molski
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: D004305:Dose-Response Relationship, Drug; D006801:Humans; D008744:Methylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D008744:Methylamines; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors