608-07-1Relevant academic research and scientific papers
Synthesis, pulse radiolysis, and in vitro radioprotection studies of melatoninolipoamide, a novel conjugate of melatonin and α-lipoic acid
Venkatachalam,Salaskar,Chattopadhyay,Barik,Mishra,Gangabhagirathi,Priyadarsini
, p. 6414 - 6419 (2006)
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.
Preparations of melatonin and 1-hydroxymelatonin, and its novel nucleophilic dimerization to (±)-3a,3a'-bispyrrolo[2,3-b]indoles
Somei, Masanori,Oshikiri, Naoki,Hasegawa, Masakazu,Yamada, Fumio
, p. 1237 - 1242 (1999)
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.
Design, Synthesis, and Biological Activity of Hydrogen Peroxide Responsive Arylboronate Melatonin Hybrids
Bedini, Annalida,Fraternale, Alessandra,Crinelli, Rita,Mari, Michele,Bartolucci, Silvia,Chiarantini, Laura,Spadoni, Gilberto
, p. 100 - 112 (2019)
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.
Method for synthesizing melatonin intermediate by taking methoxyphenamine as raw material
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, (2021/11/10)
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.
Recyclable and reusablen-Bu4NBF4/PEG-400/H2O system for electrochemical C-3 formylation of indoles with Me3N as a carbonyl source
Cheng, Didi,Li, Jingyi,Li, Yujin,Ling, Fei,Liu, Lei,Liu, Tao,Zhong, Weihui
, p. 4107 - 4113 (2021/06/17)
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.
N-skatyltryptamines-dual 5-ht6r/d2r ligands with antipsychotic and procognitive potential
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)
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.
Synthesis method of melatonin
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Paragraph 0020-0025, (2021/08/07)
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.
1-BENZYLSPIRO[PIPERIDINE-4,1′-PYRIDO[3,4-b]indole] ‘co-potentiators’ for minimal function CFTR mutants
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)
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.
Preparation method of melatonin
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Paragraph 0049; 0055; 0087-0089, (2020/03/03)
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.
Design, synthesis and biological evaluation of tryptamine salicylic acid derivatives as potential antitumor agents
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)
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.
