25084-14-4Relevant articles and documents
Structure-antibacterial activity relationships of n-substituted-(D-/l-alaninyl) 1h-1,2,3-triazolylmethyl oxazolidinones
Phillips, Oludotun Adebayo,Udo, Edet Ekpenyong,D’silva, Roselyn Jennifer
, (2018)
Bacterial resistance towards the existing class of antibacterial drugs continues to increase, posing a significant threat to the clinical usefulness of these drugs. These increasing and alarming rates of antibacterial resistance development and the decline in the number of new antibacterial drugs’ approval continue to serve as a major impetus for research into the discovery and development of new antibacterial agents. We synthesized a series of D-/L-alaninyl substituted triazolyl oxazolidinone derivatives and evaluated their antibacterial activity against selected standard Gram-positive and Gram-negative bacterial strains. Overall, the compounds showed moderate to strong antibacterial activity. Compounds 9d and 10d (D-and L-alaninyl derivatives bearing the 3,5-dinitrobenzoyl substituent), 10e (L-alaninyl derivative bearing the 5-nitrofurancarbonyl group) and 9f and 10f (D-and L-alaninyl derivatives bearing the 5-nitrothiophene carbonyl moiety) demonstrated antibacterial activity (MIC: 2 μg/mL) against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis and Moraxella catarrhalis standard bacterial strains. No significant differences were noticeable between the antibacterial activity of the D-and L-alaninyl derivatives as a result of the stereochemistry of the compounds.
Synthesis of furan derivatives condensed with carbohydrates
De Almeida, Mauro V.,Le Hyaric, Mireille,Siqueira, Leonardo J. A.,Pinto, Luciana D.,Valle, Marcelo S.,Alves, Wendel A.
, p. 728 - 735 (2001)
Eight new furan derivatives have been prepared and characterized. These compounds were obtained by condensation of aminosugar and aminocyclitol intermediates with furan derivatives.
Synthesis of N-methylpyridine-chlorofuranformamide analogs as novel OPG up-regulators and inhibitors of RANKL-induced osteoclastogenesis
Liu, Chao,Li, Yining,Sheng, Ren,Han, Xiaowan,Bao, Li,Wang, Chenyin,Wang, Weizhi,Jiang, Xinhai,Han, Jiangxue,Lei, Lijuan,Li, Ni,Zhang, Jing,Chen, Minghua,Li, Yan,Wu, Yexiang,Li, Shunwang,Ren, Yu,Xu, Yanni,Si, Shuyi
, (2021/09/28)
The OPG/RANKL/RANK pathway is a promising target for the design of therapeutic agents used in the treatment of osteoporosis. E09241 with an N-methylpyridine-chlorofuranformamide structural skeleton was previously identified to decrease bone loss and thus protect against osteoporosis in ovariectomized rats through increasing osteoprotegerin (OPG) expression. In this study, 36 derivatives of E09241 (3a) were prepared. The synthesis, up-regulation of OPG activities, SAR (structure–activity relationship), and cytotoxicity of these compounds are presented. Compounds with good up-regulating OPG activities could inhibit RANKL (the receptor activator of nuclear factor-kappa B ligand)-induced osteoclastogenesis in RAW264.7 cells. Particularly, compounds 3c and 3i1 significantly reduced NFATc1 and MMP-9 protein expression through inhibition of the NF-κB and MAPK pathways in RANKL induced RAW264.7 cells. In addition, compounds 3c and 3v significantly promoted osteoblast differentiation in MC3T3-E1 cells in osteogenic medium, and compounds 3c, 3v, and 3i1 obviously increased OPG protein expression and secretion in MC3T3-E1 cells. Furthermore, the pharmacokinetic profiles, acute toxicity, and hERG K+ channel effects of compounds 3a, 3c, 3e, 3v, and 3i1 were investigated. Taken together, these results indicate that N-methylpyridine-chlorofuranformamide analog 3i1 could serve as a promising lead for the development of new agents for treating osteoporosis.
Synthesis and Evaluation of Nifurtimox–Adamantane Adducts with Trypanocidal Activity
Foscolos, Angeliki-Sofia,Papanastasiou, Ioannis,Tsotinis, Andrew,Taylor, Martin C.,Kelly, John M.
supporting information, p. 1227 - 1231 (2019/07/09)
The synthesis and pharmacological evaluation of C1-substituted adamantane hydrazones, their C2-substituted isomers, and C1-substituted adamantane furanoic carboxamides is described. These new adamantane derivatives exhibited an interesting pharmacological profile in terms of trypanocidal activity and selectivity. The most active adduct with the best selectivity in this study was found to be the phenylacetoxy hydrazone 1 b (2-[4-(tricyclo[3.3.1.13,7]dec-1-yl)phenyl]-N′-[(5-nitrofuran-2-yl)methylene]acetohydrazide; EC50=11±0.9 nm, SITb=770).
ANTIBACTERIAL THERAPEUTICS AND PROPHYLACTICS
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Paragraph 00312; 00314, (2017/02/24)
The present disclosure relates generally to novel molecules, compositions, and formulations for treatment of bacterial infections in general and more specifically to bacterial infections with antibiotic resistant pathogens.
Rational design of nitrofuran derivatives: Synthesis and valuation as inhibitors of Trypanosoma cruzi trypanothione reductase
Arias,Herrera,Garay,Rodrigues,Forastieri,Luna,Bürgi,Prieto,Iglesias,Cravero,Guerrero
, p. 1088 - 1097 (2016/11/13)
The rational design and synthesis of a series of 5-nitro-2-furoic acid analogues are presented. The trypanocidal activity against epimastigote forms of Trypanosoma cruzi and the toxic effects on human HeLa cells were tested. Between all synthetic compounds, three of thirteen had an IC50value in the range of Nfx, but compound 13 exhibited an improved effect with an IC50of 1.0?±?0.1?μM and a selective index of 70 in its toxicity against HeLa cells. We analyzed the activity of compounds 8, 12 and 13 to interfere in the central redox metabolic pathway in trypanosomatids, which is dependent of reduced trypanothione as the major pivotal thiol. The three compounds behaved as better inhibitors of trypanothione reductase than Nfx (Ki values of 118?μM, 61?μM and 68?μM for 8, 12 and 13, respectively, compared with 245?μM for Nfx), all following an uncompetitive enzyme inhibition pattern. Docking analysis predicted a binding of inhibitors to the enzyme-substrate complex with binding energy calculated in-silico that supports such molecular interaction.
Dual role of Rh(III) catalyst enables regioselective halogenation of (electron-rich) heterocycles
Schr?der, Nils,Lied, Fabian,Glorius, Frank
supporting information, p. 1448 - 1451 (2015/02/19)
The Rh(III)-catalyzed selective bromination and iodination of electron-rich heterocycles is reported. Kinetic investigations show that Rh plays a dual role in the bromination, catalyzing the directed halogenation and preventing the inherent halogenation of these substrates. As a result, this method gives highly selective access to valuable halogenated heterocycles with regiochemistry complementary to those obtained using uncatalyzed approaches, which rely on the inherent reactivity of these classes of substrates. Furans, thiophenes, benzothiophenes, pyrazoles, quinolones, and chromones can be applied.
Development of novel tetrahydrothieno[2,3-c]pyridine-3-carboxamide based Mycobacterium tuberculosis pantothenate synthetase inhibitors: Molecular hybridization from known antimycobacterial leads
Samala, Ganesh,Devi, Parthiban Brindha,Nallangi, Radhika,Sridevi, Jonnalagadda Padma,Saxena, Shalini,Yogeeswari, Perumal,Sriram, Dharmarajan
, p. 1938 - 1947 (2014/03/21)
Twenty six 2,6-disubstituted 4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3- carboxamide derivatives were designed by molecular hybridization approach using and synthesized from piperidin-4-one by five step synthesis. Compounds were evaluated for Mycobacterium tuberculosis (MTB) pantothenate synthetase (PS) inhibition study, in vitro activities against MTB, cytotoxicity against RAW 264.7 cell line. Among the compounds, 6-(4-nitrophenylsulfonyl)-2-(5- nitrothiophene-2-carboxamido)-4,5,6,7-tetrahydrothieno[2,3-c] pyridine-3-carboxamide (11) was found to be the most active compound with IC50 of 5.87 ± 0.12 μM against MTB PS, inhibited MTB with MIC of 9.28 μM and it was non-cytotoxic at 50 μM. The binding affinity of the most potent inhibitor 11 was further confirmed biophysically through differential scanning fluorimetry.
A class of 5-nitro-2-furancarboxylamides with potent trypanocidal activity against Trypanosoma brucei in vitro
Zhou, Linna,Stewart, Gavin,Rideau, Emeline,Westwood, Nicholas J.,Smith, Terry K.
supporting information, p. 796 - 806 (2013/03/28)
Recently, the World Health Organization approved the nifurtimox- eflornithine combination therapy for the treatment of human African trypanosomiasis, renewing interest in nitroheterocycle therapies for this and associated diseases. In this study, we have synthesized a series of novel 5-nitro-2-furancarboxylamides that show potent trypanocidal activity, ～1000-fold more potent than nifurtimox against in vitro Trypanosoma brucei with very low cytotoxicity against human HeLa cells. More importantly, the most potent analogue showed very limited cross-resistance to nifurtimox-resistant cells and vice versa. This implies that our novel, relatively easy to synthesize and therefore cheap, 5-nitro-2-furancarboxylamides are targeting a different, but still essential, biochemical process to those targeted by nifurtimox or its metabolites in the parasites. The significant increase in potency (smaller dose probably required) has the potential for greatly reducing unwanted side effects and also reducing the likelihood of drug resistance. Collectively, these findings have important implications for the future therapeutic treatment of African sleeping sickness.
Wnt inhibition correlates with human embryonic stem cell cardiomyogenesis: A structure-activity relationship study based on inhibitors for the Wnt response
Lanier, Marion,Schade, Dennis,Willems, Erik,Tsuda, Masanao,Spiering, Sean,Kalisiak, Jaroslaw,Mercola, Mark,Cashman, John R.
supporting information; experimental part, p. 697 - 708 (2012/04/10)
Human embryonic stem cell-based high-content screening of 550 known signal transduction modulators showed that one "lead" (1, a recently described inhibitor of the proteolytic degradation of Axin) stimulated cardiomyogenesis. Because Axin controls canonical Wnt signaling, we conducted an investigation to determine whether the cardiogenic activity of 1 is Wnt-dependent, and we developed a structure-activity relationship to optimize the cardiogenic properties of 1. We prepared analogues with a range of potencies (low nanomolar to inactive) for Wnt/β-catenin inhibition and for cardiogenic induction. Both functional activities correlated positively (r 2 = 0.72). The optimal compounds induced cardiogenesis 1.5-fold greater than 1 at 30-fold lower concentrations. In contrast, no correlation was observed for cardiogenesis and modulation of transforming growth factor β (TGFβ)/Smad signaling that prominently influences cardiogenesis. Taken together, these data show that Wnt signaling inhibition is essential for cardiogenic activity and that the pathway can be targeted for the design of druglike cardiogenic molecules.
