Homotryptamines as potent and selective serotonin reuptake inhibitors (SSRIs).
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.
Schmitz
William D
WD
Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-7660, USA. william.schmitz@bms.com
Denhart
Derek J
DJ
Brenner
Allison B
AB
Ditta
Jonathan L
JL
Mattson
Ronald J
RJ
Mattson
Gail K
GK
Molski
Thaddeus F
TF
Macor
John E
JE
D002460:Cell Line; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008956:Models, Chemical; D015394:Molecular Structure; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D014363:Tryptamines / Q000737:chemistry* / Q000494:pharmacology*
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014363:Tryptamines; C493230:SLC6A4 protein, human