29095-44-1Relevant academic research and scientific papers
Noncompetitive inhibition of indolethylamine-N-methyltransferase by N, N-dimethyltryptamine and N, N-dimethylaminopropyltryptamine
Chu, Uyen B.,Vorperian, Sevahn K.,Satyshur, Kenneth,Eickstaedt, Kelsey,Cozzi, Nicholas V.,Mavlyutov, Timur,Hajipour, Abdol R.,Ruoho, Arnold E.
, p. 2956 - 2965 (2014)
Indolethylamine-N-methyltransferase (INMT) is a Class 1 transmethylation enzyme known for its production of N,N-dimethyltryptamine (DMT), a hallucinogen with affinity for various serotonergic, adrenergic, histaminergic, dopaminergic, and sigma-1 receptors. DMT is produced via the action of INMT on the endogenous substrates tryptamine and S-adenosyl-l-methionine (SAM). The biological, biochemical, and selective small molecule regulation of INMT enzyme activity remain largely unknown. Kinetic mechanisms for inhibition of rabbit lung INMT (rabINMT) by the product, DMT, and by a new novel tryptamine derivative were determined. After Michaelis-Menten and Lineweaver-Burk analyses had been applied to study inhibition, DMT was found to be a mixed competitive and noncompetitive inhibitor when measured against tryptamine. The novel tryptamine derivative, N-[2-(1H-indol-3-yl)ethyl]-N′,N′-dimethylpropane-1,3-diamine (propyl dimethyl amino tryptamine or PDAT), was shown to inhibit rabINMT by a pure noncompetitive mechanism when measured against tryptamine with a Ki of 84 μM. No inhibition by PDAT was observed at 2 mM when it was tested against structurally similar Class 1 methyltransferases, such as human phenylethanolamine-N-methyltransferase (hPNMT) and human nicotinamide-N- methyltransferase (hNNMT), indicating selectivity for INMT. The demonstration of noncompetitive mechanisms for INMT inhibition implies the presence of an inhibitory allosteric site. In silico analyses using the computer modeling software Autodock and the rabINMT sequence threaded onto the human INMT (hINMT) structure (Protein Data Bank entry 2A14) identified an N-terminal helix-loop-helix non-active site binding region of the enzyme. The energies for binding of DMT and PDAT to this region of rabINMT, as determined by Autodock, were ～6.34 and ～7.58 kcal/mol, respectively. Assessment of the allosteric control of INMT may illuminate new biochemical pathway(s) underlying the biology of INMT.
Synthesis and evaluation of N1-alkylindole-3-ylalkylammonium compounds as nicotinic acetylcholine receptor ligands
Perez, Edwin G.,Cassels, Bruce K.,Eibl, Christoph,Guendisch, Daniela
supporting information; experimental part, p. 3719 - 3727 (2012/08/08)
In this study thirty-three novel indole derivatives were designed and synthesized based on the structure of deformylflustrabromine B (1), a metabolite isolated from the marine bryozoan Flustra foliacea L. The syntheses were carried out using standard methodologies and in good yields. The molecules were tested for their affinities for the α4β2*, α3β 4*, α7* and (α1)2β1γδ nicotinic acetylcholine receptor (nAChR) subtypes. Binding assays showed that, among these ligands, compound 7c exhibited the highest affinity with K i = 136.1, 93.9 and 862.4 nM for the α4β2*, α3β4*, and α7* nAChRs subtypes, respectively. These results indicated that the indole core might be a useful scaffold for the development of new potent and selective nAChR ligands.
Synthesis of deuterium labeled tryptamine derivatives
Wang, Yu-Yun,Chen, Chinpiao
, p. 1363 - 1368 (2008/02/13)
The synthesis of deuterium labeled tryptamine derivatives, [2-(1H-indol-3-yl)-[2H4]-ethyl]-dimethylamine (DMT), [2H10]-diethyl-[2-(1H-indol-3-yl)-ethyl]-amine (DET), [2-(1H-indol-3-yl)-ethyl]-[2H6]-dipropyl-amine (DPT) and [2H2]-alpha-methyltryptamine (AMT) is described. The isotopically labeled compounds are used as internal standards in gas chromatography-mass spectrometry (GC-MS) assays.
Improved Synthesis of Isogranulatimide, a G2 Checkpoint Inhibitor. Syntheses of Didemnimide C, Isodidemnimide A, Neodidemnimide A, 17-Methylgranulatimide, and Isogranulatimides A-C
Piers, Edward,Britton, Robert,Andersen, Raymond J.
, p. 530 - 535 (2007/10/03)
A concise, improved synthesis of isogranulatimide (6), a naturally occurring substance with G2 checkpoint inhibition activity, is described. Also reported are the syntheses of didemnimide C (18), isodidemnimide A (24), neodidemnimide A (36), 17-methylgranulatimide (9), and isogranulatimides A (10), B (11), and C (12). Compounds 9-12, congeners of isogranulatimide (6), are now available for biological evaluation.
SIMPLE SYNTHESES OF LESPEDAMINE AND 5-BROMO-N,N-DIMETHYLTRYPTAMINE BASED ON 1-HYDROXYINDOLE CHEMISTRY
Somei, Masanori,Kobayashi, Kensuke,Tanii, Keiko,Mochizuki, Toshihiko,Kawada, Yumiko,Fukui, Yoshikazu
, p. 119 - 122 (2007/10/02)
Various types of 1-hydroxyindoles were prepared for the first time.Through methylation or acid catalyzed nucleophilic bromination of N,N-dimethyl-1-hydroxytryptamine, simple syntheses of lespedamine and 5-bromo-N,N-dimethyltryptamine were achieved, respectively.
