Conformationally restricted homotryptamines. Part 4: Heterocyclic and naphthyl analogs of a potent selective serotonin reuptake inhibitor.
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.
Dalton King
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Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway, Wallingford, CT 06492-7660, USA. dalton.king@bms.com
Denhart
Derek J
DJ
Deskus
Jeffrey A
JA
Ditta
Jonathan L
JL
Epperson
James R
JR
Higgins
Mendi A
MA
Kung
Joyce E
JE
Marcin
Lawrence R
LR
Sloan
Charles P
CP
Mattson
Gail K
GK
Molski
Thaddeus F
TF
Krause
Rudolph G
RG
Bertekap
Robert L
RL
Lodge
Nicholas J
NJ
Mattson
Ronald J
RJ
Macor
John E
JE
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*
D050483:Dopamine Plasma Membrane Transport Proteins; D006571:Heterocyclic Compounds; D050484:Norepinephrine Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014363:Tryptamines; C030820:tryptamine