23041-45-4Relevant academic research and scientific papers
Indole-based novel small molecules for the modulation of bacterial signalling pathways
Biswas, Nripendra Nath,Kutty, Samuel K.,Barraud, Nicolas,Iskander, George M.,Griffith, Renate,Rice, Scott A.,Willcox, Mark,Black, David Stc.,Kumar, Naresh
, p. 925 - 937 (2014)
Gram-negative bacteria such as Pseudomonas aeruginosa use N-acylated l-homoserine lactones (AHLs) as autoinducers (AIs) for quorum sensing (QS), a major regulatory and cell-to-cell communication system for social adaptation, virulence factor production, biofilm formation and antibiotic resistance. Some bacteria use indole moieties for intercellular signaling and as regulators of various bacterial phenotypes important for evading the innate host immune response and antimicrobial resistance. A range of natural and synthetic indole derivatives have been found to act as inhibitors of QS-dependent bacterial phenotypes, complementing the bactericidal ability of traditional antibiotics. In this work, various indole-based AHL mimics were designed and synthesized via the 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and N,N′-dicyclohexylcarbodiimide (DCC) mediated coupling reactions of a variety of substituted or unsubstituted aminoindoles with different alkanoic acids. All synthesized compounds were tested for QS inhibition using a P. aeruginosa QS reporter strain by measuring the amount of green fluorescent protein (GFP) production. Docking studies were performed to examine their potential to bind and therefore inhibit the target QS receptor protein. The most potent compounds 11a, 11d and 16a showed 44 to 65% inhibition of QS activity at 250 μM concentration, and represent promising drug leads for the further development of anti-QS antimicrobial compounds.
Synthesis of 3-nitroindoles by sequential paired electrolysis
Kilmartin, Paul A.,Lindsay, Ashley C.,Sperry, Jonathan
supporting information, p. 7903 - 7913 (2021/09/28)
3-Nitroindoles are synthetically versatile intermediates but current methods for the preparation hinder their widespread application. Herein, we report that nitroenamines undergo electrochemical cyclisation to 3-nitroindoles in the presence of potassium iodide. Detailed control experiments and cyclic voltammogram studies infer the reaction proceedsviaa sequential paired electrolysis process, beginning with anodic oxidation of iodide (I?) to the iodine radical (I˙), which facilitates cyclisation of the nitroenamine to give a 3-nitroindolinyl radical. Cathodic reduction and protonation generates a 3-nitroindoline that upon oxidation forms the 3-nitroindole.
An iron(iii)-catalyzed dehydrogenative cross-coupling reaction of indoles with benzylamines to prepare 3-aminoindole derivatives
Chen, Wei-Li,Li, Kun,Liang, Cui,Liang, Wang-Fu,Liao, Wei-Cong,Mo, Dong-Liang,Qiu, Pei-Wen,Su, Gui-Fa
, p. 9610 - 9616 (2021/12/09)
We report a green cascade approach to prepare a variety of 3-aminoindole derivatives in good to excellent yields through an iron(iii)-catalyzed dehydrogenative cross-coupling reaction of 2-arylindoles and primary benzylamines under mild reaction conditions. Mechanistic studies show that a cascade reaction involves a tert-butyl nitrite (TBN)-mediated nitrosation of 2-substituted indoles and a 1,5-hydrogen shift to afford indolenine oximes, sequential iron(iii)-catalyzed condensation and a 1,5-hydrogen shift over four steps in a one-pot reaction. The reaction shows a broad substrate scope of indoles and benzylamines and tolerates a wide range of functional groups. Moreover, the reaction is easily performed at the gram scale without producing waste after the reaction is completed. The 3-aminoindole product is purified by simple extraction, washing, and recrystallization without flash column chromatography. A double imine ligand containing the 3-aminoindole unit is facile to obtain in a 52% yield in one step. The present method highlights readily available starting materials, a simple purification procedure, and the usage of cheap, nontoxic, and environmentally benign iron(iii) catalysts. This journal is
The Trifluoromethyl Group as a Bioisosteric Replacement of the Aliphatic Nitro Group in CB1 Receptor Positive Allosteric Modulators
Tseng, Chih-Chung,Baillie, Gemma,Donvito, Giulia,Mustafa, Mohammed A.,Juola, Sophie E.,Zanato, Chiara,Massarenti, Chiara,Dall'Angelo, Sergio,Harrison, William T. A.,Lichtman, Aron H.,Ross, Ruth A.,Zanda, Matteo,Greig, Iain R.
supporting information, p. 5049 - 5062 (2019/05/28)
The first generation of CB1 positive allosteric modulators (e.g., ZCZ011) featured a 3-nitroalkyl-2-phenyl-indole structure. Although a small number of drugs include the nitro group, it is generally not regarded as being "drug-like", and this is particularly true for aliphatic nitro groups. There are very few case studies where an appropriate bioisostere replaced a nitro group that had a direct role in binding. This may be indicative of the difficulty of replicating its binding interactions. Herein, we report the design and synthesis of ligands targeting the allosteric binding site on the CB1 cannabinoid receptor, in which a CF3 group successfully replaced the aliphatic NO2. In general, the CF3-bearing compounds were more potent than their NO2 equivalents and also showed improved in vitro metabolic stability. The CF3 analogue (1) with the best balance of properties was selected for further pharmacological evaluation. Pilot in vivo studies showed that (±)-1 has similar activity to (±)-ZCZ011, with both showing promising efficacy in a mouse model of neuropathic pain.
NaNO2/K2S2O8-mediated Selective Radical Nitration/Nitrosation of Indoles: Efficient Approach to 3-Nitro- and 3-Nitrosoindoles
Shoberu, Adedamola,Li, Cheng-Kun,Tao, Ze-Kun,Zhang, Guo-Yu,Zou, Jian-Ping
supporting information, p. 2255 - 2261 (2019/04/13)
JPZ acknowledges financial support from the National Natural Science Foundation of China (No. 21172163, 21472133), the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), and Key Laboratory of Organic Synthesis of Jiangsu Province (KJS1749). (Figure presented.).
Development, Scope, and Applications of Titanium(III)-Catalyzed Cyclizations to Aminated N-Heterocycles
Leijendekker, Leonardus H.,Weweler, Jens,Leuther, Tobias M.,Kratzert, Daniel,Streuff, Jan
, p. 3382 - 3390 (2019/02/14)
The exceptionally mild conditions of a titanium(III)-catalyzed cyclization reaction paired with a convenient acid/base extraction have enabled the straightforward synthesis, isolation, and direct N-functionalization of amino heterocycles such as 3-aminoindoles and -pyrroles. The unprotected heterocycles are ideal building blocks for the installation of aminated indoles and pyrroles into target molecules, but their sensitivity has previously impeded their synthesis by modern catalytic methods. This full paper presents the development and extended scope of the new cyclization methodology. The transformation of the products into fused bis-indoles is also demonstrated along with the discovery of an unusual palladium-catalyzed reductive biphenyl coupling reaction. The titanium(III)-catalyzed cyclization has also been applied to the synthesis of substituted 3-iminoindolines, which are of potential interest for applications in natural product synthesis and exhibit tunable blue-to-green fluorescence properties.
Unusual formation of novel highly substituted N-(3-indolyl)-imidazoles
Qu, Ji,Bhadbhade, Mohan,Kumar, Naresh,Black, David StC.
, p. 7438 - 7441 (2018/11/23)
Treatment of 3-amidoindoles with phosphoryl chloride leads to a dimerization of the resulting iminochlorides to form tetrasubstituted imidazoles in moderate yield. One indole ring undergoes ring-opening to allow the formation of the imidazole ring. This s
Catalytic Reductive Synthesis and Direct Derivatization of Unprotected Aminoindoles, Aminopyrroles, and Iminoindolines
Leijendekker, Leonardus H.,Weweler, Jens,Leuther, Tobias M.,Streuff, Jan
, p. 6103 - 6106 (2017/05/22)
A titanium(III)-catalyzed radical cyclization to unprotected 3-aminoindoles, 3-aminopyrroles, or 3-iminoindolines is reported. The reaction is non-hazardous, scalable, and allows facile isolation of the free products by extraction. The method is demonstrated on a large substrate scope and it further allows the direct installation of various nitrogen protecting groups or the synthesis of building blocks for peptide chemistry in a single sequence. Fused bisindoles can be directly accessed from the cyclization products.
I2-mediated regioselective C-3 azidation of indoles
Prasad, Pragati K.,Kalshetti, Rupali G.,Reddi, Rambabu N.,Kamble, Sanjay P.,Sudalai, Arumugam
supporting information, p. 3027 - 3030 (2016/03/19)
An unprecedented synthesis of novel 3-azido indoles has been developed using I2 and NaN3 in high yields and excellent regioselectivity. The reaction proceeds under metal-free conditions at room temperature. Essentially, an umpolung in reactivity at the C-3 position of indole has been achieved by the activation of indoles with I2.
A versatile synthetic route to 11H-indolo[3,2-c]isoquinolines
Qu, Ji,Kumar, Naresh,Alamgir, Mahiuddin,Black, David StC.
scheme or table, p. 5628 - 5630 (2011/02/22)
A wide variety of indoloisoquinoline derivatives are prepared from the acid-catalyzed cyclization of 3-amido-2-phenylindoles, which in turn were obtained from the Beckmann rearrangement of 2-phenylindole-3-oximes.
