2491-38-5Relevant articles and documents
Synthesis and cardiovascular activity of metoprolol analogues
Melgar-Fernandez, Roberto,Demare, Patricia,Hong, Enrique,Rosas, Miguel Angel,Escalante, Jaime,Munoz-Muniz, Omar,Juaristi, Eusebio,Regla, Ignacio
, p. 191 - 194 (2004)
The synthesis of four novel analogues of metoprolol, a well-known β1-blocker used to reduce arterial blood pressure, is described. The preparation of (2S,2′S)-7, (2R,2′S)-7, (2R,2′R)-8, and (2S,2′R)-8 was based on the reaction of racemic 2-[4-(2′- methoxyethyl)-phenoxymethyl]-oxirane (4) with (R)- or (S)-2-amino-1-butanol. Salient characteristics of analogues 7 and 8 relative to metoprolol are the incorporation of an additional stereogenic center, as well as a methyl group and a hydroxyl function on the nitrogen-containing chain. These novel derivatives present significant hypotensive and bradycardiac activity, although no blocking action toward β1 and β2 adrenergic receptor.
Easy synthesis of β-O-4 type lignin related polymers
Kishimoto, Takao,Uraki, Yasumitsu,Ubukata, Makoto
, p. 1067 - 1073 (2005)
The β-O-4 structure is the most abundant substructure in lignin. Lignin related polymers composed of only the β-O-4 structure were prepared using simple aromatic compounds as starting materials. Acetophenone derivatives were brominated, polymerized in the presence of K2CO3 and reduced with NaBH4 to give the lignin related polymers. These are linear polymers which resemble natural lignins in their structures, although they do not have a γ-hydroxymethyl group. The number average degree of polymerization (DPn) was determined with peracetate of the polymers by gel permeation chromatography. The DPn of guaiacyl type polymers ranged from 15.2-21.4, where the value for the syringyl type was 11.3 and for the p-hydroxyphenyl type 16.9. The Guaiacyl type polymer was very soluble in usual lignin solvents such as 1,4-dioxane-water (96:4, v/v) and DMSO, but only slightly soluble in acetone-water (9:1, v/v). The Royal Society of Chemistry 2005.
First synthesis of tabamides A–C and their derivatives: In vitro nitric oxide inhibitory activity
Damodar, Kongara,Jeon, Sung Ho,Lee, Jeong Tae,Shin, Sooyong
supporting information, (2021/11/10)
The first synthesis of natural phenolic amides, tabamides A–C (1–3), and their derivatives (4–12) was accomplished using Stobbe condensation and amide coupling reactions as key steps. The in vitro nitric oxide (NO) inhibitory effects of these compounds in LPS-induced RAW-264.7 macrophages were evaluated as an indicator of anti-inflammatory activity. All compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without significant cytotoxicity. Compound 6, a tabamide A derivative (IC50 = 82.6 μM), followed by tabamide A (1, IC50 = 100.7 μM), was the most potent from the series. The present study revealed that tabamide A (1) could be considered as a lead structure to develop NO production-targeted anti-inflammatory agents.
Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer
Bantzi, Marina,Augsburger, Fiona,Loup, Jérémie,Berset, Yan,Vasilakaki, Sofia,Myrianthopoulos, Vassilios,Mikros, Emmanuel,Szabo, Csaba,Bochet, Christian G.
, p. 6221 - 6240 (2021/05/06)
The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is one of the more recently identified mammalian sources of H2S. A recent study identified several novel 3-MST inhibitors with micromolar potency. Among those, (2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one) or HMPSNE was found to be the most potent and selective. We now took the central core of this compound and modified the pyrimidone and the arylketone sides independently. A 63-compound library was synthesized; compounds were tested for H2S generation from recombinant 3-MST in vitro. Active compounds were subsequently tested to elucidate their potency and selectivity. Computer modeling studies have delineated some of the key structural features necessary for binding to the 3-MST's active site. Six novel 3-MST inhibitors were tested in cell-based assays: they exerted inhibitory effects in murine MC38 and CT26 colon cancer cell proliferation; the antiproliferative effect of the compound with the highest potency and best cell-based activity (1b) was also confirmed on the growth of MC38 tumors in mice.
Nucleus-independent chemical shift (NICS) as a criterion for the design of new antifungal benzofuranones
González-Chávez, Marco Martín,González-Chávez, Rodolfo,Méndez, Francisco,Martínez, Roberto,Ni?o-Moreno, Perla Del Carmen,Ojeda-Fuentes, Luis Enrique,Richaud, Arlette,Zerme?o-Macías, María de los ángeles
, (2021/08/30)
The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p –1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 μg·mL–1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.
Benzo[d]thiazole-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl as potent selectivelasBquorum sensing inhibitors of Gram-negative bacteria
Quoc, Thang Nguyen,Thanh, Tung Truong,Xuan, Huy Luong
, p. 28797 - 28808 (2021/09/22)
Quorum sensing is a well-known term for describing bacterial cell-cell communication. Bacteria use quorum sensing pathways to respond to external factors such as nutrient availability, defense mechanisms, and coordinate host toxic behaviors such as biofilm formation, virulence production, and other pathogenesis. Discovery of novel compounds which inhibit quorum sensing without being antibiotic are currently emerging fields. Herein, the library of fifteen benzo[d]thiazole/quinoline-2-thiol bearing 2-oxo-2-substituted-phenylethan-1-yl compounds was designed, synthesized and evaluated to find novel quorum sensing inhibitors. Firstly, compounds were evaluated for their growth inhibitory activities at high concentrations up to 1000 μg mL?1towardPseudomonas aeruginosa. Under our conditions, twelve compounds showed moderate growth inhibitory activities in the concentration tested. To our delight, three compounds3,6and7do not affect the growth of the bacteria which were chosen for the evaluation of quorum sensing inhibitor activities. In theLasBsystem, our compounds3,6,7showed promising quorum-sensing inhibitors with IC50of 115.2 μg mL?1, 182.2 μg mL?1and 45.5 μg mL?1, respectively. In thePqsRsystem, no activity observed suggesting that the selectivity of the compound toward theLasBsystem. In addition,7showed the moderate anti-biofilm formation ofPseudomonas aeruginosa. Docking studies revealed that3,6and7binding to the active site ofPseudomonas aeruginosaquorum sensingLasRsystem with better affinity compared to reference compounds4-NPO. Finally, computation calculations suggest that compounds are a good template for further drug development.
Synthesis and preliminary photopolymerization evaluation of novel photoinitiators containing phototrigger to overcome oxygen inhibition in the UV- curing system
Chen, Wenbin,Wang, Lei,Liu, Xinyue,Chen, Bo,Zhao, Guofeng
, (2019/11/26)
In this work, two types of novel photoinitiaors containing phototrigger were prepared to overcome oxygen inhibition in the UV- curing system in the absence of hydrogen donor. The structures of prepared novel photoinitiators were determined by nuclear magnetic resonance (NMR) and high resolution MS (HR[sbnd]MS) spectra data. The photo chemical behavior and photo-reactivity were also evaluated by ultraviolet-visible (UV–vis) spectroscopy and real-time Fourier transform infrared spectroscopy (RT-FTIR), respectively. The results show the prepared photoinitiators exhibit remarkable redshift compared to the commercial BP (benzophenone) and Irgacure 907 (2-methyl-1-(4-methylsulfanylphenyl)-2-morpholin-4-ylpropan-1-one), fast photolysis by C[sbnd]S bond, good photo initiation and significant overcoming oxygen inhibition for some compounds, which can be used as one-component photoinitiator candidates.
Novel thiazole–pyrazolone hybrids as potent ACE inhibitors and their cardioprotective effect on isoproterenol-induced myocardial infarction
You, Hongwen,Su, Xinyou,Su, Guoying
, (2020/08/27)
A facile synthesis of a group of novel thiazole–pyrazolone hybrids and their investigation for angiotensin-converting enzyme (ACE) inhibition are reported in this study. These compounds were synthesized using a well-known approach, based on the condensation of ethyl acetoacetate with thiazolylhydrazines, and characterized by various spectroscopic and analytical techniques. The entire set of compounds displayed a moderate-to-excellent inhibitory activity against ACE. In particular, compound 4i was found to be the most potent ACE inhibitor and was further studied for cardioprotective effects against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Compound 4i improved the cardiac function and prevented cardiac injury induced by ISO in Sprague Dawley rats. The levels of oxidative stress and proinflammatory cytokines were also restored to near normal by 4i as compared with the ISO group. In the Western blot analysis, compound 4i prevented mitochondrial apoptosis after MI by downregulating the expression of cleaved caspase-3 and Bax, with the upregulation of Bcl-2, as compared with the ISO group.
Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study
Ma, Weifeng,Chen, Peng,Huo, Xiansen,Ma, Yufeng,Li, Yanhong,Diao, Pengcheng,Yang, Fang,Zheng, Shengquan,Hu, Mengjin,You, Wenwei,Zhao, Peiliang
, (2020/10/08)
Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 μM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.
ANTIBACTERIAL COMPOUNDS
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Page/Page column 85-86, (2019/05/22)
The present invention relates to compounds of general formula (II),to compositions comprising these compounds and to methods of treating Enterobacteriaceae bacterial diseases and infections using the compounds. The compounds find application in the treatment of infection with, and diseases caused by, Enterobacteriaceae.
