78596-42-6Relevant academic research and scientific papers
Rapid room temperature liquid phase synthesis of diethyl 2-((4-nitroanilino) methylene)malonate
Valle, Hernán,Mangalaraja, Ramalinga Viswanathan,Rivas, Bernabé L.,Becerra, José,Naveenraj, Selvaraj
, p. 4098 - 4101 (2018)
Diethyl 2-((4-nitroanilino)methylene)malonate [4-NANM-E] is an important molecule owing to its role of precursor in the multistage synthesis of several quinoline derivatives possessing biological activities such as antiviral, immunosuppressive, anticancer and photoprotector. This molecule is usually synthesized by a nucleophilic vinyl substitution (SNV) between 4-nitroaniline and diethylethoxymethylene malonate (EMA). Although several procedures are available to synthesize 4-NANM-E in liquid phase, more convenient method is necessary to synthesize in less reaction time and at room temperature. In this study, it is demonstrated that equimolar amounts of EMA and 4-nitroaniline dissolved in alcoholic KOH react within a few seconds at room temperature to produce 4-NANM-E which is purified by simple filtration after acidification with aqueous HCl and washing with alcohol. The reaction has the yield varying at the range 45-53% when it occurs in ethanol, 2-propanol, 2-butanol or 2-pentanol. Therefore, this synthesis method is an excellent alternative to produce 4-NANM-E on an industrial scale.
Intramolecular resonance assisted N–H???O=C hydrogen bond and weak noncovalent interactions in two asymmetrically substituted geminal amido-esters: Crystal structures and quantum chemical exploration
Ilangovan, Andivelu,Percino, M. Judith,Thamotharan, Subbiah,Venkatesan, Perumal
, (2021/08/10)
Two asymmetrically substituted geminal amido-esters, namely ethyl (2E)-2-[(2,5-dimethoxy phenyl)carbamoyl]-3-[(4-nitrophenyl)amino] prop-2-enoate (I) and ethyl (2E)-2-[(9,10-dioxo-9,10-dihydroanthracen-1-yl)carbamoyl]-3-(phenylamino) prop-2-enoate (II) were synthesized and the nature and strength of intramolecular resonance assisted hydrogen bond (RAHB) and non-RAHB was studied. X-ray analysis revealed that intramolecular N–H???O, and C–H???O interactions lead to the formation of angularly fused pseudo tricyclic (A-C) motif in compound I and fused pseudo pentacyclic (A-E) motif in compound II. Intramolecular RAHB; non-RAHB interactions are characterized and quantified by Bader's quantum theory of atoms-in-molecules approach (QTAIM). In both compounds, ring A was found to exhibit intramolecular RAHB characteristics. Crystal structures of I and II are stabilized by weak intermolecular C–H???O, C–H???π, and π???π interactions. Intermolecular interaction energies for different molecular dimers in I and II have been quantified by using the PIXEL, QTAIM, and DFT methods. The pseudoring stacking interaction is observed only in compound II whereas no such stacking interactions are seen in compound I. Hirshfeld surface (HS) analysis suggested that the H???H and O???H contacts are the first and second dominant contacts in both crystal structures. The theoretical charge density analysis revealed that the C–H???O and C–H???C(π) interactions produce closed-shell characteristics. Further, the crystal packing of compounds I and II analyzed based on the energy frameworks.
Easy-to-access quinolone derivatives exhibiting antibacterial and anti-parasitic activities
Beteck, Richard M.,Hoppe, Heinrich C.,Jordaan, Audrey,Khanye, Setshaba D.,Laming, Dustin,Seldon, Ronnett,Warner, Digby F.
, (2021/06/11)
The cell wall of Mycobacterium tuberculosis (Mtb) has a unique structural organisation, comprising a high lipid content mixed with polysaccharides. This makes cell wall a formidable barrier impermeable to hydrophilic agents. In addition, during host infection, Mtb resides in macrophages within avascular necrotic granulomas and cavities, which shield the bacterium from the action of most antibiotics. To overcome these protective barriers, a new class of anti-TB agents exhibiting lipophilic character have been recommended by various reports in literature. Herein, a series of lipophilic heterocyclic quinolone compounds was synthesised and evaluated in vitro against pMSp12::GFP strain of Mtb, two protozoan parasites (Plasmodium falciparum and Trypanosoma brucei brucei) and against ESKAPE pathogens. The resultant compounds exhibited varied anti-Mtb activity with MIC90 values in the range of 0.24-31 μM. Cross-screening against P. falciparum and T.b. brucei, identified several compounds with antiprotozoal activities in the range of 0.4-20 μM. Compounds were generally inactive against ESKAPE pathogens, with only compounds 8c, 8g and 13 exhibiting moderate to poor activity against S. aureus and A. baumannii.
6-Nitro-1-benzylquinolones exhibiting specific antitubercular activity
Beteck, Richard M.,Jordaan, Audrey,Swart, Tarryn,Van Der Kooy, Frank,Warner, Digby F.,Hoppe, Heinrich C.,Legoabe, Lesetja J.
, p. 1387 - 1394 (2020/07/28)
In this study, we synthesized novel nitro quinolone-based compounds and tested them in vitro against a panel of Gram-positive and Gram-negative pathogens including Mycobacterium tuberculosis (MTB), Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumonia, Staphylococcus aureus, and Escherichia coli for antibacterial activities and also against HeLa cells for overt cytotoxicity. Compound 8e was identified as a non-toxic, potent hit with selective activity (MIC90???0.24?μm) against MTB. 8e, however, showed no activity against DprE1 mutant, suggesting DprE1 as the likely target for this compound class.
Insights into supramolecular assembly formation of diethyl aryl amino methylene malonate (DAM)derivatives assisted via non-covalent interactions
Shaik, Althaf,Angira, Deekshi,Thiruvenkatam, Vijay
, p. 178 - 185 (2019/05/14)
The crystal structures of four derivatives of diethyl 2-(((aryl)amino)methylene)malonate (DAM)have been studied by single crystal X-ray diffraction. The molecular structures of all the four derivatives were found to be in co-planar conformation. The detailed analysis of molecular conformation in four derivatives reveals the presence of a common strong intramolecular N–H?O hydrogen bonding, forming a ring of graph-set motif S1 1 (6). The effect of chloro and nitro substitution on their relative strengths of hydrogen bonding are analyzed here. Particularly, in compound 1, additional intramolecular hydrogen bonding between –NO2 and N–H was observed that results in the formation of another six-membered chelate ring. On the other hand in case of compound 3, we have observed type-I Cl?Cl interaction for the first time in this class of compounds. Further, Hirshfeld surface has been generated that is mapped with dnorm shape index and curvedness to summarize the weak interactions and examine the molecular shapes in all four derivatives. Effect of nitro (1 and 2)and chloro (3 and 4)substitution on the C?H, N?O and C?O interaction is highlighted in molecular contour and 2D fingerprint plots.
1,2,3-Triazolyl-4-oxoquinolines: A feasible beginning for promising chemical structures to inhibit oseltamivir-resistant influenza A and B viruses
Boechat, Fernanda Da C.S.,Sacramento, Carolina Q.,Cunha, Anna C.,Sagrillo, Fernanda S.,Nogueira, Christiane M.,Fintelman-Rodrigues, Natalia,Santos-Filho, Osvaldo,Riscado, Cecília S.,Forezi, Luana Da S.M.,Faro, Letícia V.,Brozeguini, Leonardo,Marques, Isakelly P.,Ferreira, Vitor F.,Souza, Thiago Moreno L.,De Souza, Maria Cecília B.V.
, p. 7777 - 7784 (2015/12/18)
We described the synthesis of a new congener series of 1,2,3-triazolyl-4-oxoquinolines and evaluated their ability to inhibit oseltamivir (OST)-resistant influenza strains. Oxoquinoline derivative 1i was the most potent compound within this series, inhibiting 94% of wild-type (WT) influenza neuraminidase (NA) activity. Compound 1i inhibited influenza virus replication with an EC50 of 0.2 μM with less cytotoxicity than OST, and also inhibited different OST-resistant NAs. These results suggest that 1,2,3-triazolyl-4-oxoquinolines represent promising lead molecules for further anti-influenza drug design.
Synthesis of 6-ethyl-1,2,9-trioxopyrrolo[3,2-f ]quinoline-8-carboxylic acid
Al-As'ad, Randa M.,El-Abadelah, Mustafa M.,Sabri, Salim S.,Zahra, Jalal A.,Voelter, Wolfgang
, p. 700 - 706 (2013/07/26)
Interaction of 6-amino-1-ethyl-4-oxoquinoline-3-carboxylic ester (7) with chloral hydrate and hydroxylamine hydrochloride gave the corresponding isonitroso-acetamido derivative 8 which, upon treatment with concentrated sulfuric acid, was converted regioselectively into 1,2,9-trioxopyrrolo[3,2-f] quinoline-8-carboxylic acid (3). This novel tricyclic system was isolated in good yield as a stable hydrate 3H. Structural assignments of the new compounds are based on microanalytical and spectral (MS and NMR) data.
Further studies on bis-charged tetraazacyclophanes as potent inhibitors of small conductance Ca2+-activated K+ channels
Yang, Donglai,Arifhodzic, Lejla,Ganellin, C. Robin,Jenkinson, Donald H.
, p. 907 - 923 (2013/07/27)
Previously, quinolinium-based tetraazacyclophanes, such as UCL 1684 and UCL 1848, have been shown to be extraordinarily sensitive to changes in chemical structure (especially to the size of the cyclophane system) with respect to activity as potent non-peptidic blockers of the small conductance Ca 2+-activated K+ ion channels (SKCa). The present work has sought to optimize the structure of the linking chains in UCL 1848. We report the synthesis and SKCa channel-blocking activity of 29 analogues of UCL 1848 in which the central CH2 of UCL 1848 is replaced by other groups X or Y = O, S, CF2, CO, CHOH, CC, CHCH, CHMe to explore whether subtle changes in bond length or flexibility can improve potency still further. The possibility of improving potency by introducing ring substituents has also been explored by synthesizing and testing 25 analogues of UCL 1684 and UCL 1848 with substituents (NO2, NH2, CF 3, F, Cl, CH3, OCH3, OCF3, OH) in the 5, 6 or 7 positions of the aminoquinolinium rings. As in our earlier work, each compound was assayed for inhibition of the afterhyperpolarization (AHP) in rat sympathetic neurons, an action mediated by the SK3 subtype of the SK Ca channel. One of the new compounds (39, R7 = Cl, UCL 2053) is twice as potent as UCL 1848 and UCL 1684: seven are comparable in activity.
Oxoquinoline acyclonucleoside phosphonate analogues as a new class of specific inhibitors of human immunodeficiency virus type 1
Faro, Leticia V.,De Almeida, Jessica M.,Cirne-Santos, Claudio C.,Giongo, Viveca A.,Castello-Branco, Luis R.,Oliveira, Ingrid De B.,Barbosa, Juliana E.F.,Cunha, Anna C.,Ferreira, Vitor F.,De Souza, Marcos C.,Paixao, Izabel C.N.P.,De Souza, Maria Cecilia B.V.
scheme or table, p. 5055 - 5058 (2012/08/28)
The emergence of a multidrug-resistant HIV-1 strain and the toxicity of anti-HIV-1 compounds approved for clinical use are the most significant problems facing antiretroviral therapies. Therefore, it is crucial to find new agents to overcome these issues. In this study, we synthesized a series of new oxoquinoline acyclonucleoside phosphonate analogues (ethyl 1- [(diisopropoxyphosphoryl)methyl]-4-oxo-1,4-dihydroquinoline-3-carboxylates 3a-3k), which contained different substituents at the C6 or C7 positions of the oxoquinoline nucleus and an N1-bonded phosphonate group. We subsequently investigated these compounds' in vitro inhibitory effects against HIV-1-infected peripheral blood mononuclear cells (PBMCs). The most active compounds were the fluoro-substituted derivatives 3f and 3g, which presented excellent EC 50 values of 0.4 ± 0.2 μM (3f) and 0.2 ± 0.005 μM (3g) and selectivity index values (SI) of 6240 and 14675, respectively.
Synthesis and anticancer activities of some novel 2-(benzo[d]thiazol-2-yl)- 8-substituted-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones
Reis, Raísa Da R.,Azevedo, Elisa C.,De Souza, Maria Cecília B.V.,Ferreira, Vitor Francisco,Montenegro, Raquel C.,Araújo, Ana Jérsia,Pessoa, Cláudia,Costa-Lotufo, Letícia V.,De Moraes, Manoel O.,Filho, José D.B.M.,De Souza, Alessandra M.T.,De Carvalho, Natasha C.,Castro, Helena C.,Rodrigues, Carlos R.,Vasconcelos, Thatyana R.A.
experimental part, p. 1448 - 1452 (2011/04/24)
A series of 2-(benzo[d]thiazol-2-yl)-8-substituted-2H-pyrazolo[4,3-c] quinolin-3(5H)-ones (3a-g) have been synthesized and evaluated for their in vitro antiproliferative activities against four human cancer cell lines: MDA-MB-435 (breast), HL-60 (leukemia), HCT-8 (colon) and SF-295 (central nervous system). The results showed that the compounds 3b (2-(benzo[d]thiazol-2-yl)-8- methyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-one) and 3c (2-(benzo[d]thiazol-2-yl)-8- bromo-2H-pyrazolo[4,3-c]quinolin-3(5H)-one) exhibited good cytotoxicity for three cell lines with IC50 values lower than 5 μg/mL. Analysis of theoretical toxicity risks have shown medium tumorigenic and irritant risks related to 3b and 3c in contrast to doxorubicin, the positive control.
