Topic
Substituted tryptamine
About: Substituted tryptamine is a research topic. Over the lifetime, 20 publications have been published within this topic receiving 194 citations. The topic is also known as: tryptamine & substituted tryptamine.
Papers
TL;DR: Using the ergoline lysergic acid diethylamide (LSD), and a series of substituted tryptamine and phenethylamine 5-HT2A receptor agonists, it is found that Ser5.43(239) is more critical for agonist binding and function than S5.46(242), which is consistent with the functional topography and utility of the in silico-activated homology model of the h5-HT 2A receptor.
Abstract: We assessed the relative importance of two serine residues located near the top of transmembrane helix 5 of the human 5-HT(2A) receptor, comparing the wild type with S5.43(239)A or S5.46(242)A mutations. Using the ergoline lysergic acid diethylamide (LSD), and a series of substituted tryptamine and phenethylamine 5-HT(2A) receptor agonists, we found that Ser5.43(239) is more critical for agonist binding and function than Ser5.46(242). Ser5.43(239) seems to engage oxygen substituents at either the 4- or 5-position of tryptamine ligands and the 5-position of phenylalkylamine ligands. Even when a direct binding interaction cannot occur, our data suggest that Ser5.43(239) is still important for receptor activation. Polar ring-substituted tryptamine ligands also seem to engage Ser5.46(242), but tryptamines lacking such a substituent may adopt an alternate binding orientation that does not engage this residue. Our results are consistent with the role of Ser5.43(239) as a hydrogen bond donor, whereas Ser5.46(242) seems to serve as a hydrogen bond acceptor. These results are consistent with the functional topography and utility of our in silico-activated homology model of the h5-HT(2A) receptor. In addition, being more distal from the absolutely conserved Pro5.50, a strong interaction with Ser5.43(239) may be more effective in straightening the kink in helix 5, a feature that is possibly common to all type A GPCRs that have polar residues at position 5.43.
61 citations
TL;DR: Careful design of new molecules based on a proposed pharmacophoric model of the 5HT1B-like receptor has resulted in the discovery of ethyl 3-[2-(dimethylamino)ethyl]-5-[2, 5-dioxo-1-imidazolidinyl]ethyl]-1H-indole-2-carboxylate (40), a highly potent, silent, competitive, and selective antagonist.
Abstract: The design, synthesis, and activity of a novel series of 2,5-substituted tryptamine derivatives at vascular 5HT 1B -like receptors is described. Several important auxiliary binding sites of the 5HT 1B -like receptor have been proposed following various modifications to the 2-substituent and especially to the methylene- or ethylene-linked 5-side chain. Careful design of new molecules based on a proposed pharmacophoric model of the 5HT 1B -like receptor has resulted in the discovery of ethyl 3-[2-(dimethylamino)ethyl]-5-[2-(2,5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxylate (40), a highly potent, silent, competitive, and selective antagonist which shows affinity at the vascular 5HT 1B -like receptors only. Changes to the size of the 2-ester substituent have a significant effect on affinity at the 5HT 1B -like receptor and other receptors. Prudent placement of the carbonyl substituent in the heterocycle of the 5-side chain is crucial for good affinity and selectivity over the 5HT 2A and other receptors. Several key structural and electronic features were identified which are crucial for producing antagonism within a tryptamine-based series. An electron deficient indole ring system appears essential in order to achieve antagonism, and this is achieved by the inclusion of electron-withdrawing groups at the 2-position of the indole ring. The molecule displacement within the receptor resulting from the inclusion of the bulky 2-substituents also enhances antagonism as this results in the removal of the electon density of the indole ring from the region of the receptor normally occupied by the indole ring of 5HT. There also appears to be a structural requirement on the side chain incorporating the protonatable nitrogen, and this is achieved by the inclusion of the bulky 2-ester group which neighbors the 3-ethylamine side chain.
42 citations
TL;DR: This catalytic, single-step, and modular approach to tryptamines and homotryptamines allows the synthesis of branched and nonbranchedtryptamines as well as tryptamine-based natural products such as psilocin, bufotenin, and serotonin.
32 citations
TL;DR: Three different acetylenic analogues of tryptamine, in which the side chain is attached at the 2 position of the heterocyclic ring, were studied as inhibitors of MAO-A andMAO-B to define the kinetic parameters defining non-covalent complex formation and covalent adduct formation.
Abstract: Three different acetylenic analogues of tryptamine, in which the side chain is attached at the 2 position of the heterocyclic ring, were studied as inhibitors of MAO-A and MAO-B.
18 citations
Patent•
29 Mar 1995
TL;DR: In this paper, an antibiotic, NEMATOPHIN, is drawn to 3-indoleethyl 3-methyl-2-oxo-pentanamide (+stereoisomer, stereoisomer and racemic mixture) and its derivatives.
Abstract: The invention is drawn to an antibiotic, NEMATOPHIN, 3-indoleethyl 3'-methyl-2-oxo-pentanamide (+stereoisomer, -stereoisomer and racemic mixture) and its derivatives, 3-indoleethyl 2-oxo-alkanamides, 3-indoleethyl 2-oxo-alkanoates with or without substitute(s) on the indole ring, produced by bacterial symbiont Xenorhabdus nematophilus and/or other Xenorhabdus species or synthesized by reaction of tryptamine or substituted tryptamine and 2-oxo-alkanoic acid or its derivative, the additional salts thereof, the pharmaceutical compositions thereof and their use as medicaments, particularly in the treatment of infectious diseases involving microorganisms susceptible to them, including antibiotic-resistant Staphylococcus.
15 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2019 | 1 |
| 2016 | 2 |
| 2014 | 2 |
| 2008 | 1 |
| 2007 | 1 |
| 2004 | 1 |