Synthesis and preliminary screening of novel tryptamines as 5-HT4 receptor ligands.
For the development of novel 5-HT(4) receptor ligands we have designed and synthesized two series of 5-methoxytryptamine derivatives varying the substitution on the primary amine. Their biological activities were evaluated in a receptor binding assay where a subset of compounds showed comparable potency to the agonists serotonin and 5-methoxytryptamine. Structure-activity analyses have highlighted promising avenues for further synthetic work and binding modes were proposed by docking these compounds into a homology model of the 5-HT(4) receptor.
Hanna-Elias
A
A
Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia.
Manallack
D T
DT
Berque-Bestel
I
I
Irving
H R
HR
Coupar
I M
IM
Iskander
M N
MN
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D015195:Drug Design; D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D044422:Receptors, Serotonin, 5-HT4 / Q000378:metabolism / Q000502:physiology; D058832:Serotonin 5-HT4 Receptor Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D014363:Tryptamines / Q000819:agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D008024:Ligands; D058832:Serotonin 5-HT4 Receptor Antagonists; D014363:Tryptamines; D044422:Receptors, Serotonin, 5-HT4; D008735:5-Methoxytryptamine