Homotryptamines as potent and selective serotonin reuptake inhibitors (SSRIs)

William D Schmitz; Derek J Denhart; Allison B Brenner; Jonathan L Ditta; Ronald J Mattson; Gail K Mattson; Thaddeus F Molski; John E Macor

doi:10.1016/j.bmcl.2005.01.059

Homotryptamines as potent and selective serotonin reuptake inhibitors (SSRIs)

Bioorg Med Chem Lett. 2005 Mar 15;15(6):1619-21. doi: 10.1016/j.bmcl.2005.01.059.

Authors

William D Schmitz¹, Derek J Denhart, Allison B Brenner, Jonathan L Ditta, Ronald J Mattson, Gail K Mattson, Thaddeus F Molski, John E Macor

Affiliation

¹ Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-7660, USA. william.schmitz@bms.com

PMID: 15745809
DOI: 10.1016/j.bmcl.2005.01.059

Abstract

A series of N,N-dimethylhomotryptamines was prepared and their binding affinities at the serotonin transporter (SERT) were determined. Compounds possessing an electron withdrawing substituent at the C5-position of the indole nucleus were found to be potent SSRIs. Initial attempts at conformational restriction of the propylamine sidechain by incorporation of a quinuclidine bicyclic structure did not improve binding affinity at SERT.

MeSH terms

Cell Line
Humans
Membrane Glycoproteins / metabolism
Membrane Transport Proteins / metabolism
Models, Chemical
Molecular Structure
Nerve Tissue Proteins / metabolism
Protein Binding
Selective Serotonin Reuptake Inhibitors / chemistry*
Selective Serotonin Reuptake Inhibitors / pharmacology*
Serotonin Plasma Membrane Transport Proteins
Tryptamines / chemistry*
Tryptamines / pharmacology*

Substances

Membrane Glycoproteins
Membrane Transport Proteins
Nerve Tissue Proteins
SLC6A4 protein, human
Serotonin Plasma Membrane Transport Proteins
Serotonin Uptake Inhibitors
Tryptamines