cas 608-07-1, 5-Methoxytryptamine | Articles data

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Synthesis, pulse radiolysis, and in vitro radioprotection studies of melatoninolipoamide, a novel conjugate of melatonin and α-lipoic acid
A novel conjugate of melatonin 2 and α-lipoic acid 4 has been prepared using DCC mediated coupling. The conjugate named melatoninolipoamide has been assigned its structure 1 on the basis of spectral analysis (UV, IR, NMR, and EI-MS). Pulse radiolysis studies of the conjugate were carried out in aqueous solutions with both oxidizing and reducing radicals. The results indicate that the melatonin moiety of the conjugate reacts preferably with oxidizing radicals and the lipoic acid moiety exhibits preferential reaction with reducing radicals. The in vitro radioprotection ability of 1 was examined by γ-radiation induced lipid peroxidation in liposomes and hemolysis of erythrocytes, and compared the results with those of melatonin and α-lipoic acid. The studies suggest that the conjugate can be explored as a probable radioprotector.
Venkatachalam,Salaskar,Chattopadhyay,Barik,Mishra,Gangabhagirathi,Priyadarsini
p. 6414 - 6419
(2006)
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Preparations of melatonin and 1-hydroxymelatonin, and its novel nucleophilic dimerization to (±)-3a,3a'-bispyrrolo[2,3-b]indoles
A unique synthetic method for melatonin was established through biologically promising synthetic intermediates. 1-Hydroxymelatonin was prepared as crystals for the first time. It reacted with 85% formic acid to give (±)-3a,3a'-bispyrrolo[2,3-b]indole compound, whose structure was unequivocally determined by X-Ray crystallographic analysis.
Somei, Masanori,Oshikiri, Naoki,Hasegawa, Masakazu,Yamada, Fumio
p. 1237 - 1242
(1999)
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Design, Synthesis, and Biological Activity of Hydrogen Peroxide Responsive Arylboronate Melatonin Hybrids
Stimulus-responsive cleavage reactions have found broad use to direct drug release at a particular target disease area. Increased levels of reactive oxygen species (ROS) have been associated with the development and progression of cancer and several other disease states, motivating the development of drug conjugates that can undergo a chemoselective ROS-triggered release. Melatonin (MLT) and the reactive electrophile p-benzoquinone methide (p-QM) have evidenced either cytoprotective or cytotoxic effects in biological systems, depending on the dose, cellular targets, and time of exposure. In this study, we report the synthesis and biological activity of two MLT derivatives linked to ROS-responsive arylboronate triggers (P1 and P2), which can be activated by endogenously generated hydrogen peroxide (H2O2) to release MLT, or 5-methoxytryptamine (5-MeOT), and p-QM-intermediates. Their H2O2-induced activation mechanism was studied by HPLC-DAD-MS. P1, which rapidly releases MLT and p-QM, was able to strongly induce the Nrf2 antioxidant signaling pathway, but was ineffective to provide protection against H2O2-mediated oxidative damage. By contrast, P1 exhibited strong toxic effects in HeLa cancer cells, without causing significant toxicity to normal NCTC-2544 cells. Similar, although more limited, effects were exerted by P2. In both cases, cytotoxicity was accompanied by depletion of cellular glutathione (GSH), probably as a consequence of p-QM release, and increased ROS levels. A role for MLT in toxicity was also observed, suggesting that the P1 released products, MLT and p-QM, contributed additively to promote cell death.
Bedini, Annalida,Fraternale, Alessandra,Crinelli, Rita,Mari, Michele,Bartolucci, Silvia,Chiarantini, Laura,Spadoni, Gilberto
p. 100 - 112
(2019)
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N-skatyltryptamines-dual 5-ht6r/d2r ligands with antipsychotic and procognitive potential
A series of N-skatyltryptamines was synthesized and their affinities for serotonin and dopamine receptors were determined. Compounds exhibited activity toward 5-HT1A, 5-HT2A, 5-HT6, and D2 receptors. Substitution patterns resulting in affinity/activity switches were identified and studied using homology modeling. Chosen hits were screened to determine their metabolism, permeability, hepatotoxicity, and CYP inhibition. Several D2 receptor antagonists with additional 5-HT6R antagonist and agonist properties were identified. The former combination resembled known antipsychotic agents, while the latter was particularly interesting due to the fact that it has not been studied before. Selective 5-HT6R antagonists have been shown previously to produce procognitive and promnesic effects in several rodent models. Administration of 5-HT6R agonists was more ambiguous-in naive animals, it did not alter memory or produce slight amnesic effects, while in rodent models of memory impairment, they ameliorated the condition just like antagonists. Using the identified hit compounds 15 and 18, we tried to sort out the difference between ligands exhibiting the D2R antagonist function combined with 5-HT6R agonism, and mixed D2/5-HT6R antagonists in murine models of psychosis.
Bojarski, Andrzej J.,Bugno, Ryszard,Cie?lik, Paulina,Duszyńska, Beata,Handzlik, Jadwiga,Hogendorf, Adam S.,Hogendorf, Agata,Kaczorowska, Katarzyna,Kurczab, Rafa?,Latacz, Gniewomir,Lenda, Tomasz,Sata?a, Grzegorz,Staroń, Jakub,Szewczyk, Bernadeta
(2021/08/17)

Synthesis method of melatonin
The invention discloses a synthesis method of melatonin, and belongs to the technical field of pharmaceutical chemistry synthesis. According to the method, 5-hydroxytryptamine hydrochloride is used as a raw material, 5-methoxytryptamine is obtained through a methylation reaction of hydroxyl through a one-pot feeding method, a crude melatonin product is prepared through an acetylation reaction of amino, and finally, the finished melatonin is obtained through one-step refining and purification. The melatonin synthesis method provided by the invention avoids waste caused by step-by-step purification of the product, and has the characteristics of short synthesis route, short synthesis period, few raw material types and the like, the obtained product is high in yield, and the purity can meet the market demand. The synthesis method of the melatonin provided by the invention saves the cost and is easy for industrial production.
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Paragraph 0020-0025

(2021/08/07)

1-BENZYLSPIRO[PIPERIDINE-4,1′-PYRIDO[3,4-b]indole] ‘co-potentiators’ for minimal function CFTR mutants
We previously identified a spiro [piperidine-4,1-pyrido [3,4-b]indole] class of co-potentiators that function in synergy with existing CFTR potentiators such as VX-770 or GLGP1837 to restore channel activity of a defined subset of minimal function cystic fibrosis transmembrane conductance regulator (CFTR) mutants. Here, structure-activity studies were conducted to improve their potency over the previously identified compound, 20 (originally termed CP-A01). Targeted synthesis of 37 spiro [piperidine-4,1-pyrido [3,4-b]indoles] was generally accomplished using versatile two or three step reaction protocols with each step having high efficiency. Structure-activity relationship studies established that analog 2i, with 6′-methoxyindole and 2,4,5-trifluorobenzyl substituents, had the greatest potency for activation of N1303K-CFTR, with EC50 ～600 nM representing an ～17-fold improvement over the original compound identified in a small molecule screen.
Son, Jung-Ho,Phuan, Puay-Wah,Zhu, Jie S.,Lipman, Elena,Cheung, Amy,Tsui, Ka Yi,Tantillo, Dean J.,Verkman, Alan S.,Haggie, Peter M.,Kurth, Mark J.
(2020/10/26)

Method for synthesizing melatonin intermediate by taking methoxyphenamine as raw material
The invention belongs to the technical field of compound synthesis, and aims to solve the problem that expensive reducing agents are needed in the present method for synthesizing melatonin, and the cost is high. The invention provides a method for synthesizing melatonin intermediate by taking methoxyphenamine as a raw material, and the like. Pt / Al with supported catalyst by taking methoxyaniline and ethylene glycol as raw materials2 O3 One-step hydrothermal method synthesizes 5 - methoxyindole and then obtains melatonin precursor 3 methoxytryptamine by 5 -step hydrothermal reaction. 5 - Methoxyindole is firstly synthesized by taking ethylene glycol and paramethoxyaniline as raw materials, then 3 methoxytryptamine is obtained through 5 - steps, and the total yield of the reaction is 14.0%. final synthesis of melatonin. A new melatonin synthesis route is designed, and the melatonin precursor 5 - methoxytryptamine is synthesized by using a raw material aniline derivative and ethylene glycol which are simple in application structure and low in cost.
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(2021/11/10)

Recyclable and reusablen-Bu4NBF4/PEG-400/H2O system for electrochemical C-3 formylation of indoles with Me3N as a carbonyl source
A safe, practical and eco-friendly electrochemical methodology for the synthesis of 3-formylated indoles has been developed by the utilization of Me3N as a novel formylating reagent. Stoichiometric oxidants, metal catalysts, and activating agents were avoided in this method, and an aqueous biphasic system ofn-Bu4NBF4/PEG-400/H2O was used as a recyclable and reusable reaction medium, which made this electrosynthesis approach more sustainable and environmentally friendly. This process expanded the substrate scope and functional group tolerance for bothN-EDG andN-EWG indoles. Furthermore, late-stage functionalization and total/formal synthesis of drugs and natural products were realized by means of this route.
Cheng, Didi,Li, Jingyi,Li, Yujin,Ling, Fei,Liu, Lei,Liu, Tao,Zhong, Weihui
p. 4107 - 4113
(2021/06/17)

Preparation method of melatonin
The invention relates to the technical field of chemical synthesis of medicines, in particular to a preparation method of melatonin. The preparation method of the melatonin comprises the following steps: (a) subjecting phthalimide, 1,3-dichloropropane, sodium iodide and ethyl acetoacetate to a reaction in a solvent under the action of alkali to obtain a compound I; (b) performing a ring closing reaction on the compound I and p-methoxyphenyl diazonium salt in the presence of alkali and a solvent to obtain a compound II; (c) hydrolyzing the compound II under an alkaline condition, and carrying out decarboxylating under an acidic condition to obtain a compound III; and (d) carrying out an acetylation reaction on the compound III to obtain melatonin. According to the preparation method, phthalimide, 1,3-dichloropropane, ethyl acetoacetate and the like are used as raw materials, and the price of the raw materials is low; the intermediate compound I can be obtained through a one-step method,so reaction steps and time are shortened; moreover, the conditions of each reaction step are relatively mild, the raw materials are easy to obtain, and high yield can be obtained.
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Paragraph 0049; 0055; 0087-0089

(2020/03/03)

Facile in Vitro Biocatalytic Production of Diverse Tryptamines
Tryptamines are a medicinally important class of small molecules that serve as precursors to more complex, clinically used indole alkaloid natural products. Typically, tryptamine analogues are prepared from indoles through multistep synthetic routes. In the natural world, the desirable tryptamine synthon is produced in a single step by l-tryptophan decarboxylases (TDCs). However, no TDCs are known to combine high activity and substrate promiscuity, which might enable a practical biocatalytic route to tryptamine analogues. We have now identified the TDC from Ruminococcus gnavus as the first highly active and promiscuous member of this enzyme family. RgnTDC performs up to 96 000 turnovers and readily accommodates tryptophan analogues with substituents at the 4, 5, 6, and 7 positions, as well as alternative heterocycles, thus enabling the facile biocatalytic synthesis of >20 tryptamine analogues. We demonstrate the utility of this enzyme in a two-step biocatalytic sequence with an engineered tryptophan synthase to afford an efficient, cost-effective route to tryptamines from commercially available indole starting materials.
McDonald, Allwin D.,Perkins, Lydia J.,Buller, Andrew R.
p. 1939 - 1944
(2019/07/08)

Design, synthesis and biological evaluation of tryptamine salicylic acid derivatives as potential antitumor agents
A series of tryptamine salicylic acid derivatives were synthesized and their antiproliferative activity against MGC-803, MCF-7, HepG2, A549 and HeLa cell lines was evaluated. The structure-activity relationship (SAR) study revealed that different substitutions of the C5 and C3′-C5′ positions have certain effects on the anti-proliferation activity. The growth assay revealed that N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide (E20) showed the most potent and broad-spectrum anticancer inhibition of all the cell lines evaluated, and was only more potent than 5-Fu for the gastric cancer cell line. Preliminary studies indicated that compound E20 could inhibit colony formation and migration of MGC-803 cells. The flow cytometry (FCM) results showed that compound E20 arrested the cell cycle in the G2/M phase and induced apoptosis of MGC-803 cells in a concentration-dependent manner. In addition, the western blot results showed that E20 can down-regulate the expression of hexokinase 2. Our studies suggest that the framework of N-[2-(5-bromo-1H-indol-3-yl)-ethyl]-2-hydroxy-3-methyl-benzamide may be consider as a new type of chemical for designing effective anti-cancer drugs targeting gastric cancer cells.
Xiong, Runde,He, Dongxiu,Deng, Xiangping,Liu, Juan,Lei, Xiaoyong,Xie, Zhizhong,Cao, Xuan,Chen, Yanming,Peng, Junmei,Tang, Guotao
p. 573 - 583
(2019/04/30)

Metal-Free Dearomatization: Direct Access to Spiroindol(en)ines in Batch and Continuous-Flow
A metal-free, phosphine-catalyzed intramolecular “umpolung Michael addition” on alkynes to form spiroindol(en)ines is reported. This nucleophilic catalysis enables the formation of a wide scope of five- and six-membered spiroindol(en)ines in moderate to excellent yields in batch as well as under continuous-flow conditions. Triphenylphosphine-catalyzed nucleophilic activation of alkynes allows the exclusive formation of exo-product under mild reaction conditions.
Ranjan, Prabhat,Ojeda, Gerardo M.,Sharma, Upendra K.,Van der Eycken, Erik V.
p. 2442 - 2446
(2019/01/29)

Rice histone deacetylase 10 and Arabidopsis histone deacetylase 14 genes encode N-acetylserotonin deacetylase, which catalyzes conversion of N-acetylserotonin into serotonin, a reverse reaction for melatonin biosynthesis in plants
In plants, melatonin production is strictly regulated, unlike the production of its precursor, serotonin, which is highly inducible in response to stimuli, such as senescence and pathogen exposure. Exogenous serotonin treatment does not greatly induce the production of N-acetylserotonin (NAS) and melatonin in plants, which suggests the possible existence of one or more regulatory genes in the pathway for the biosynthesis of melatonin from serotonin. In this report, we found that NAS was rapidly and abundantly converted into serotonin in rice seedlings, indicating the presence of an N-acetylserotonin deacetylase (ASDAC). To clone the putative ASDAC gene, we screened 4 genes that were known as histone deacetylase (HDAC) genes, but encoded proteins targeted into chloroplasts or mitochondria rather than nuclei. Of 4 recombinant Escherichia coli strains expressing these genes, one E.?coli strain expressing the rice HDAC10 gene was found to be capable of producing serotonin in response to treatment with NAS. The recombinant purified rice HDAC10 (OsHDAC10) protein exhibited ASDAC enzyme activity toward NAS, N-acetyltyramine (NAT), N-acetyltryptamine, and melatonin, with the highest ASDAC activity for NAT. In addition, its Arabidopsis ortholog, AtHDAC14, showed similar ASDAC activity to that of OsHDAC10. Both OsHDAC10 and AtHDAC14 were found to be expressed in chloroplasts. Phylogenetic analysis indicated that ASDAC homologs were present in archaea, but not in cyanobacteria, which differs from the distribution of serotonin N-acetyltransferase (SNAT). This suggests that SNAT and ASDAC may have evolved differently from ancestral eukaryotic cells.
Lee, Kyungjin,Lee, Hyoung Yool,Back, Kyoungwhan
(2018/01/15)

An environmentally friendly protocol for oxidative halocyclization of tryptamine and tryptophol derivatives
An environmentally friendly and efficient protocol (KX/oxone) for oxidative halocyclization of tryptamine/tryptophol derivatives was developed and demonstrated with 28 examples and concise total synthesis of cyclotryptamine alkaloid protubonines A and B. The distinct advantage of this protocol over all previous methods is that no organic byproduct is generated from a halogenating agent or oxidant, thus greatly reducing the environmental impact of halocyclization and facilitating the post-reaction purification.
Xu, Jun,Tong, Rongbiao
p. 2952 - 2956
(2017/07/24)

N3,N6-BIS(2-(5-METHOXY-1H-INDOLE-3-YL)ETHYL)-2,6-DIMETHYL-4-(2-NITROPHENYL)PYRIDINE-3,5-DICARBOXAMIDE AND USE THEREOF IN THE FIELD OF NEUROTOXICITY
The invention relates to a molecule enabling removal of neurotoxicity observed in neuron cells due to various reasons.
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Page/Page column 4

(2017/08/21)

Iridium-catalyzed direct synthesis of tryptamine derivatives from indoles: Exploiting N-protected β-amino alcohols as alkylating agents
The selective C3-alkylation of indoles with N-protected ethanolamines involving the "borrowing hydrogen" strategy is described. This method provides convenient and sustainable access to several tryptamine derivatives.
Bartolucci, Silvia,Mari, Michele,Bedini, Annalida,Piersanti, Giovanni,Spadoni, Gilberto
p. 3217 - 3222
(2015/03/30)

Novel difluoroacetamide analogues of agomelatine and melatonin: probing the melatonin receptors for MT1 selectivity
Synthesis and pharmacological evaluation of novel agomelatine and melatonin analogues with structures combining the features generating MT1 selectivity, namely the bulky hydrophobic ether moiety and the difluoroacetamide group, is reported. The dimeric agomelatine analogue linked by a three methylene spacer displayed the best affinity (Ki = 1.2 nM) and selectivity (7-fold) toward MT1 receptors.
Zlotos, Darius P.,Riad, Noura M.,Osman, Mai B.,Dodda, Bala R.,Witt-Enderby, Paula A.
p. 1340 - 1344
(2015/07/15)

Alpha-ethyltryptamines as dual dopamine-serotonin releasers
The dopamine (DA), serotonin (5-HT), and norepinephrine (NE) transporter releasing activity and serotonin-2A (5-HT2A) receptor agonist activity of a series of substituted tryptamines are reported. Three compounds, 7b, (+)-7d and 7f, were found to be potent dual DA/5-HT releasers and were >10-fold less potent as NE releasers. Additionally, these compounds had different activity profiles at the 5-HT2Areceptor. The unique combination of dual DA/5-HT releasing activity and 5-HT2Areceptor activity suggests that these compounds could represent a new class of neurotransmitter releasers with therapeutic potential.
Blough, Bruce E.,Landavazo, Antonio,Partilla, John S.,Decker, Ann M.,Page, Kevin M.,Baumann, Michael H.,Rothman, Richard B.
p. 4754 - 4758
(2015/01/09)

Chiral anion phase transfer of aryldiazonium cations: An enantioselective synthesis of C3-diazenated pyrroloindolines
Herein is reported the first asymmetric utilization of aryldiazonium cations as a source of electrophilic nitrogen. This is achieved through a chiral anion phase-transfer pyrroloindolinization reaction that forms C3-diazenated pyrroloindolines from simple tryptamines and aryldiazonium tetrafluoroborates. The title compounds are obtained in up to 99% yield and 96% ee. The air- and water-tolerant reaction allows electronic and steric diversity of the aryldiazonium electrophile and the tryptamine core. Live and let diazene: Chiral anion phase transfer of aryldiazonium cations has been utilized to prepare C3-diazenated pyrroloindolines. The air- and water-tolerant reaction allows electronic and steric diversity in the aryldiazonium electrophile and the tryptamine core, with the products being obtained in up to 99% yield and 96% ee (MTBE=methyl tert-butyl ether).
Nelson, Hosea M.,Reisberg, Solomon H.,Shunatona, Hunter P.,Patel, Jigar S.,Toste, F. Dean
p. 5600 - 5603
(2014/06/10)

Fischer indole synthesis in low melting mixtures
Functionalized indoles are synthezised under mild conditions in a tartaric acid-dimethylurea melt. The melt serves as the solvent and as the catalyst. Under these reaction conditions, sensitive functional groups such as N-Boc, N-Cbz, or azides are stable, and indolenines are obtained regioselectively in excellent yields. The practical use of the method is demonstrated in the synthesis of the hormone melatonin.
Gore, Sangram,Baskaran, Sundarababu,K?nig, Burkhard
p. 4568 - 4571
(2012/10/30)

Synthesis and structureactivity relationship of novel conformationally restricted analogues of serotonin as 5-HT6 receptor ligands
5-Hydroxytryptamine 6 receptors (5-HT6R) are being perceived as the possible target for treatment of cognitive disorders as well as obesity. The present article deals with the design, synthesis, in vitro binding and structureactivity relationship of a novel series of tetracyclic tryptamines with the rigidized N-arylsulphonyl, N-arylcarbonyl and N-benzyl substituents as 5-HT6 receptor ligands. The chiral sulphonyl derivatives 15a and 17a showed high affinity at 5-HT6R with the Ki of 23.4 and 20.5nM, respectively. The lead compound from the series 15a has acceptable ADME properties, adequate brain penetration and is active in animal models of cognition like Novel Object Recognition Task (NORT) and water maze.
Nirogi, Ramakrishna V.S.,Kambhampati, Ramasastri,Kothmirkar, Prabhakar,Konda, Jagadishbabu,Bandyala, Thrinath Reddy,Gudla, Parandhama,Arepalli, Sobhanadri,Gangadasari, Narasimhareddy P.,Shinde, Anil K.,Deshpande, Amol D.,Dwarampudi, Adireddy,Chindhe, Anil K.,Dubey, Pramod Kumar
p. 443 - 450
(2012/08/28)

Structure-activity relationship study of beta-carboline derivatives as haspin kinase inhibitors
Haspin is a serine/threonine kinase that phosphorylates Thr-3 of histone H3 in mitosis that has emerged as a possible cancer therapeutic target. High throughput screening of approximately 140,000 compounds identified the beta-carbolines harmine and harmol as moderately potent haspin kinase inhibitors. Based on information obtained from a structure-activity relationship study previously conducted for an acridine series of haspin inhibitors in conjunction with in silico docking using a recently disclosed crystal structure of the kinase, harmine analogs were designed that resulted in significantly increased haspin kinase inhibitory potency. The harmine derivatives also demonstrated less activity towards DYRK2 compared to the acridine series. In vitro mouse liver microsome stability and kinase profiling of a representative member of the harmine series (42, LDN-211898) are also presented.
Cuny, Gregory D.,Ulyanova, Natalia P.,Patnaik, Debasis,Liu, Ji-Feng,Lin, Xiangjie,Auerbach, Ken,Ray, Soumya S.,Xian, Jun,Glicksman, Marcie A.,Stein, Ross L.,Higgins, Jonathan M.G.
scheme or table
p. 2015 - 2019
(2012/04/05)

SEPIAPTERIN REDUCTASE INHIBITORS FOR THE TREATMENT OF PAIN
Disclosed herein are small molecule heterocyclic inhibitors of sepiapterin reductase (SPR), and pro-drugs and pharmaceutically acceptable salts thereof. The Also featured are pharmaceutical compositions of the compounds and uses of these compounds for the treatment or prevention of pain (e.g., inflammatory pain, nociceptive pain, functional pain, and neuropathic pain)
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(2011/05/05)

First total synthesis of marine alkaloid hyrtiosulawesine
Hyrtiosulawesine was isolated from Indonesian specimens of the marine sponges Hyrtios erectus and H. reticulatu in 2002. We report here the first total synthesis of hyrtiosulawesine using an efficient and convenient synthetic strategy which could be widely used in the synthesis of other β-caboline compounds. All structures of new compounds were confirmed by 1H NMR, 13C NMR and HRMS.
Zhang, Pu Yong,Wan, Sheng Biao,Ren, Su Mei,Jiang, Tao
scheme or table
p. 1307 - 1309
(2011/10/08)

INDOLE COMPOUNDS, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
Compounds of formula (I): wherein: R1 represents an alkyl, cycloalkyl or cycloalkylalkyl group,R2 and R3, together with the nitrogen atom carrying them, form a heterocycle having from 5 to 8 ring members,and n represents from 2 to 6. Medicinal products containing the same which are useful in treating disorders of the to melatoninergic system.
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Page/Page column 3

(2010/08/18)

The ideal synthetic method aimed at the leads for an α2-blocker, an inhibitor of blood platelet aggregation, and an anti-osteoporosis agent
According to the definition of the ideal synthetic method, an example aimed at the leads for an α2 blocker, an inhibitor of platelet aggregation, and an anti-osteoporosis agent is established starting from tryptamine. The originality rate, the intellectual property, and the application potential factors of the method are 71, 54, and 100, respectively. The method employs only conventional reagents and reaction conditions without using any protecting groups.{A figure is presented}.
Somei, Masanori,Iwaki, Takako,Yamada, Fumio,Tanaka, Yoshio,Shigenobu, Koki,Koike, Katsuo,Suzuki, Nobuo,Hattori, Atsuhiko
p. 1565 - 1569
(2007/10/03)

Syntheses of novel indole lipoic acid derivatives and their antioxidant effects on lipid peroxidation
The aim of the study was to examine antioxidant properties of conjugates based on indole and lipoic acid moieties. The design and syntheses of novel indole α-lipoic acid derivatives were performed. The antioxidant properties of target compounds were investigated using rat liver microsomal, NADPH-dependent lipid peroxidation inhibition. Some of the target compounds, especially those containing amide linker at position 5 of indole ring, proved to be highly effective in inhibiting lipid peroxidation as compared to α-lipoic acid.
Gurkan, A. Selen,Karabay, Arzu,Buyukbingol, Zeliha,Adejare, Adeboye,Buyukbingol, Erdem
p. 67 - 73
(2007/10/03)

Synthesis and antioxidant properties of some indole ethylamine derivatives as melatonin analogs
The synthesis and lipid peroxidation (LP) inhibition activity of several novel indole melatonin analogues are reported. Compounds have shown variable antioxidant features depending on the substitution pattern. Melatonin and the antioxidant reference compound butyl hydroxy toluen (BHT) were used to compare the antioxidant capability of the compounds synthesized.
Ates-Alagoz,Buyukbingol,Buyukbingol, Erdem
p. 643 - 647
(2007/10/03)

Microwave assisted synthesis of melatonin
Melatonin was prepared from phthalimide by N- and C-alkylation, cyclization, hydrolytic, decarboxylation, and acetylation. The four-pot reactions were carried out on microwave irradiation in good yield with short time.
He, Ling,Li, Ju-Lian,Zhang, Jian-Jun,Su, Pu,Zheng, Shi-Long
p. 741 - 747
(2007/10/03)

Efficient route to the pineal hormone melatonin by radical-based indole synthesis
The hormone melatonin, which is known to have a range of important biological effects, has been prepared in a high-yielding route that features formation of the indole nucleus by radical cyclization. Mediation of the radical cyclization by tristrimethylsilylsilane (TTMSS) is more efficient than by N-ethylpiperidine hypophosphite.
Thomson, Douglas W.,Commeureuc, Aurelien G. J.,Berlin, Stefan,Murphy, John A.
p. 3631 - 3641
(2007/10/03)

Aromatization of 1,6,7,7a-tetrahydro-2H-indol-2-ones by a novel process. Preparation of key-intermediate methyl 1-benzyl-5-methoxy-1H-indole-3-acetate and the syntheses of serotonin, melatonin, and bufotenin
Imine 7 of 1,4-cyclohexanedione mono-ethylene ketal 6 was reacted with maleic anhydride, affording the cyclized adduct 8. Methyl esterification of 8, accompanied by transacetalization, led to the dihydrooxindole derivative 10. Aromatization of 10 was then accomplished with POCl3, leading directly to the key-intermediate title compound 11 in 74% yield from ketone 6. Serotonin, melatonin, and bufotenin were then obtained by standard reactions.
Revial, Gilbert,Jabin, Ivan,Lim, Sethy,Pfau, Michel
p. 2252 - 2256
(2007/10/03)

A versatile linkage strategy for solid-phase synthesis of N,N-dimethyltryptamines and β-carbolines
(matrix presented) Various tryptamines are captured by a vinylsulfonylmethyl polystyrene resin, generating a safety-catch linkage. β-Carbolines can be formed from 4 by a Pictet-Spengler reaction with the introduction of R1. Tryptamine 4 can also be derivatized by acylation or copper-mediated coupling to introduce R2. If X = Br, Suzuki coupling can be used to introduce R3. After derivatization, the indole derivatives are activated with methyl iodide and released under mild basic condition.
Wu, Tom Y. H.,Schulte, Peter G.
p. 4033 - 4035
(2007/10/03)

Preparation and reactions of 4-, 5-, and 6-methoxy substituted 3-lithioindoles and 3-indolylzinc derivatives
The preparation of 4-, 5-, and 6-methoxy substituted 3-lithio-1-(trialkylsilyl)indoles 4b-d by metalation of the corresponding 3-bromoindoles, and their reactions with iodomethane, DMF, ethylene oxide and aziridines are reported. Transmetalation of 3-lithioindoles 4b-d with ZnCl2 afforded 3-indolylzinc chlorides 11b-d, which underwent Pd(0)-catalyzed cross-coupling reactions with 2-halopyridines to give 4-, 5-, and 6-methoxy substituted 3-(2-pyridyl)indoles.
Amat,Seffar,Llor,Bosch
p. 267 - 275
(2007/10/03)

Melatonin-antagonist beta -carboline derivatives and analogues thereof containing naphthalenic structure, process for their preparation and their use as medicinal products
The present invention provides beta -carboline derivatives useful as components of cosmetic, medicinal, and pharmaceutical compositions. The medicinal and pharmaceutical compositions can be used to induce hypnotic activity in a subject. Methods of producing the beta -carboline derivatives are provided as well.
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(2008/06/13)

Syntheses of melatonin and its derivatives
Two simple synthetic methods for melatonin are newly developed from tryptamine through intermediates, which are promising lead compounds for drug developing research. Novel chemical reactivities of melatonin in its bromination, lithiation, and acylation are also reported.
Somei, Masanori,Fukui, Yoshikazu,Hasegawa, Masakazu,Oshikiri, Naoki,Hayashi, Toshikatsu
p. 1725 - 1736
(2007/10/03)

Process research and development of melatonin
A short, simple, and industrially feasible process for the preparation of melatonin (N-acetyl-5-methoxy tryptamine), starting from phthalimide and 1-bromo-3-chloropropane, in essentially four steps is discussed. The present article elucidates the preparative process along with the impurity profile of each intermediate.
Prabhakar,Kumar, N. Vasanth,Reddy, M. Ravikanth,Sarma,Reddy, G. Om
p. 155 - 160
(2013/09/08)

METHOD OF INHIBITING GASTRIC ACID SECRETION WITH BENZODIOXANES
The present invention provides a method of inhibiting gastric acid secretion in mammals by administering a 5-HT1A agonist compound or a pharmaceutically acceptable salt thereof.
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(2008/06/13)

METHOD OF INHIBITING GASTRIC ACID SECRETION
The present invention provides a method of inhibiting gastric acid secretion in mammals by administering a 5-HT1A agonist compound or a pharmaceutically acceptable salt thereof.
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(2008/06/13)

Method of solubilizing melatonine in water
A method of synthesizing an indole derivative of the tryptamine type particularly melatonine, comprising the steps of 1) reacting potassium phthalimide and 1,3-di-bromopropane to obtain 3-bromopropylphthalimide; 2) reacting 3-bromopropylphthalimide with sodium acetoacetic ester in ethanol to obtain ethyl-2-acetyl-5-phthalimidopentanoate; 3) reacting the product from step 2) with diazo-p-anisidine to obtain 2-carboxyethyl-3-(2-phthalimidoethyl)-5-methoxy-indole; 4) reacting the 2-carboxyethyl-3-(2-phthalimidoethyl)-5-methoxy-indole with 2N/NaOH and then 20% H2 SO4 to obtain impure 5-methoxytriptamine, which is purified by means of hexamethyldisilazane. The mono and disubstituted derivatives are obtained and the monosubstituted derivative is hydrolyzed with aqueous methanol and then recrystallized from ethanol. The N-acetyl derivative is prepared by reaction with acetic anhydride. Melatonine of high purity is obtained for prophylaxy and also against AIDS (Acquired Immuno Deficiency Syndrome).
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(2008/06/13)

Psychotomimetic N-Methyl-N-isopropyltryptamines. Effects of Variation of Aromatic Oxygen Substituents
Eight N-methyl-N-isopropyltryptamines (MIPTs) possessing various aromatic oxygen substituents were prepared, characterized, and evaluated for hallucinogenic activity in man.In at least two instances (the Ar H and the Ar 5-OCH3, 1 and 4) the unsymmetrical nitrogen substitution led to a substantial increase in potency as well as oral activity when compared to the symmetrical dimethyl homologues.Qualitatively, 4-hydroxy-N-methyl-N-isopropyltryptamine (2) was the most interesting in overall effect, producing a classic hallucinogenic profile.The 5-methoxy congeger 4 resulted in a state characterized by heightened conceptual stimulation lacking in visual phenomena.Other members of the series exhibited diminished effects.
Repke, David B.,Grotjahn, Douglas B.,Shulgin, Alexander T.
p. 892 - 896
(2007/10/02)

Preparation of serotonine and derivatives
A process for the separation of serotonine from coffee wax wherein a solution of coffee wax is subjected to alkaline hydrolysis using a strong base in the presence of water in an inert atmosphere after which the reaction medium containing the serotonine is recovered characterized in that the solvent for the coffee wax is a compound having the general formula II: wherein R is hydrogen or an alkyl group containing from 1 to 4 carbon atoms, x is 0 or 1 and n is an integer from 2 to 4 with the proviso that x cannot be 1 when n is 3 or 4. N-acetyl serotonine is prepared by acetylating serotonine to N, O-diacetyl serotonine and then selectively hydrolyzing the O-acetyl group. Melatonine is obtained by methylating N-acetyl serotonine in the 5-position. Mexamine is obtained by de-acetylating melatonine in a hot alkaline solution containing a water-insoluble alcohol and acidifying the alcohol phase with hydrochloric acid.
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(2008/06/13)

Synthesis and evaluation of the antiovulatory activity of a variety of melatonin analogues
A series of melatonin analogues was synthesized and examined for ovulation-blocking activity. Deviation from the 5-methoxy group or substitution of the 1 position prevented activity. Activity was not particularly sensitive to minor variations in the N-acyl group nor was it significantly altered by methylation of position 2 or the α-methylene; however, a pronounced enhancement resulted from halogenation of the 6 position.
Flaugh,Crowell,Clemens,Sawyer
p. 63 - 69
(2007/10/04)