19005-93-7Relevant articles and documents
Molecular Structure and Photochemistry of (E)- and (Z)-Ethyl 3-(2-Indolyl)propenoate. Ground State Conformational Control of Photochemical Behavior and One-Way E -> Z Photoisomerization
Lewis, Frederick D.,Yang, Jye-Shane
, p. 14560 - 14568 (1996)
The molecular structure, electronic spectra, and photoisomerization of (E)- and (Z)-ethyl 3-(2-indolyl)propenoate, two methylated indole derivatives, and their N,N-dimethylamide analog have been investigated.The E ester exists in the ground state as a mixture of anti and syn rotational isomers.The spectroscopic and photochemical behaviors of the individual anti and syn conformers were characterized with the assistance of comparisons with the behavior of the methylated indole derivatives.The major anti conformer of the E ester absorbs and emits at shorter wavelength than the minor syn conformer.The rate constant for singlet state isomerization of the anti conformer is substantially larger than that of the syn conformer, resulting in a shorter singlet lifetime and smaller fluorescence quantum yield for the anti conformer.The behavior of the E amide in both the ground and excited states is similar to that of the ester.The Z isomers of the ester and amide possess a relatively strong intramolecular hydrogen bond.Their singlet states are weakly fluoroscent and photoisomerize ineffeciently in nonpolar solvents.Thus photostationary states highly enriched in the Z isomers are obtained in nonpolar solvents.The red-shifted, structureless emission observed upon irradiating the Z amide in an EPA or methylcyclohexane glass at 77 K is attributed to an excited state tautomer formed via intramolecular hydrogen transfer.
Synthesis and antibacterial evaluation of (E)-1-(1H-indol-3-yl) ethanone O-benzyl oxime derivatives against MRSA and VRSA strains
Akunuri, Ravikumar,Veerareddy, Vaishnavi,Kaul, Grace,Akhir, Abdul,Unnissa, Tanveer,Parupalli, Ramulu,Madhavi,Chopra, Sidharth,Nanduri, Srinivas
supporting information, (2021/08/27)
Infections caused due to multidrug resistant organisms have emerged as a constant menace to human health. Even though numerous antibiotics are currently available for treating infectious diseases, a great number of bacterial strains have acquired resistance to many of them. Among these, infections caused due to Staphylococcus aureus are predominant in adult and paediatric population. Indole is a prominent chemical scaffold found in many pharmacologically active natural products and synthetic drugs. A number of oxime ether containing compounds have attracted attention of researchers owing to their interesting biological properties. Current work details the synthesis of indole containing oxime ether derivatives and their evaluation for antimicrobial activity against a panel of bacterial and mycobacterial strains. Synthesized compounds demonstrated good to moderate activity against drug-resistant S. aureus including resistant to vancomycin. Among all, compound 5h was found to possess potent activity against susceptible as well as MRSA and VRSA strains of S. aureus with MIC of 1 μg/mL and 2–4 μg/mL respectively. In addition, compound 5h was found to be non-toxic to Vero cells and exhibited good selectivity index of >40. Further, 5h, E-9a and E-9b possessed good biofilm inhibition against S. aureus. With these assuring biological properties, synthesized compounds could be potential prospective antimicrobial agents.
Amide-Amine Replacement in Indole-2-carboxamides Yields Potent Mycobactericidal Agents with Improved Water Solubility
Tan, Yu Jia,Li, Ming,Gunawan, Gregory Adrian,Nyantakyi, Samuel Agyei,Dick, Thomas,Go, Mei-Lin,Lam, Yulin
supporting information, p. 704 - 712 (2020/11/30)
Indolecarboxamides are potent but poorly soluble mycobactericidal agents. Here we found that modifying the incipient scaffold by amide-amine substitution and replacing the indole ring with benzothiophene or benzoselenophene led to striking (10-20-fold) im
Au(I)-Catalyzed Pictet-Spengler Reactions All around the Indole Ring
Milcendeau, Pierre,Zhang, Zhenhao,Glinsky-Olivier, Nicolas,Van Elslande, Elsa,Guinchard, Xavier
, p. 6406 - 6422 (2021/05/29)
Au(I) complexes catalyze iso-Pictet-Spengler reactions. Ethylamine or methylamine chains were introduced at C2, C4, or the nitrogen atom of the indole ring, and the corresponding substrates were reacted in the presence of aldehydes and catalytic amounts of Au(I) complexes, leading to a variety of polycyclic scaffolds. Selectivity could be achieved in the course of a double iso-Pictet-Spengler reaction involving two successive aldehydes, leading to highly complex molecules.
Synthesis and evaluation of cyclic nitrone derivatives as potential anti-cancer agents
Zhou, Wei,Ju, Dongyan,Ao, Yuhui,Liu, Yu,Zhao, Jinbo
, p. 1309 - 1316 (2021/05/27)
Nitrones have been found to exhibit attractive biological values as immuno spin trapping agents. However, successful clinical cases of nitrone therapeutics are still lacking. Herein we report the synthesis and antiproliferative activity of a series of structurally diverse nitrone derivatives against a panel of 5 cancer cell lines, based on which indole- and pyrrole-fused were further evaluated by analogue preparation and in-vitro screening. Analogues with moderate to good potency were identified. This study shows the promise for further pursuit of nitrone-type small molecules in chemotherapy. [Figure not available: see fulltext.]
Potent Inhibition of Nicotinamide N-Methyltransferase by Alkene-Linked Bisubstrate Mimics Bearing Electron Deficient Aromatics
Buijs, Ned,Campagna, Roberto,Emanuelli, Monica,Gao, Yongzhi,Innocenti, Paolo,Jespers, Willem,Martin, Nathaniel I.,Parsons, Richard B.,Sartini, Davide,Van Haren, Matthijs J.,Van Westen, Gerard J. P.,Zhang, Yurui,Gutiérrez-De-Terán, Hugo
, p. 12938 - 12963 (2021/09/11)
Nicotinamide N-methyltransferase (NNMT) methylates nicotinamide (vitamin B3) to generate 1-methylnicotinamide (MNA). NNMT overexpression has been linked to a variety of diseases, most prominently human cancers, indicating its potential as a therapeutic target. The development of small-molecule NNMT inhibitors has gained interest in recent years, with the most potent inhibitors sharing structural features based on elements of the nicotinamide substrate and the S-adenosyl-l-methionine (SAM) cofactor. We here report the development of new bisubstrate inhibitors that include electron-deficient aromatic groups to mimic the nicotinamide moiety. In addition, a trans-alkene linker was found to be optimal for connecting the substrate and cofactor mimics in these inhibitors. The most potent NNMT inhibitor identified exhibits an IC50 value of 3.7 nM, placing it among the most active NNMT inhibitors reported to date. Complementary analytical techniques, modeling studies, and cell-based assays provide insights into the binding mode, affinity, and selectivity of these inhibitors.
Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation
Chelvam, Venkatesh,Dudhe, Premansh,Krishnan, Mena Asha,Pathak, Biswarup,Roy, Diptendu,Venkatasubbaiah, Krishnan,Yadav, Kratika
supporting information, p. 1453 - 1463 (2021/07/02)
1,5-Disubstituted indole-2-carboxaldehyde derivatives 1a–h and glycine alkyl esters 2a–c are shown to undergo a novel cascade imination-heterocylization in the presence of the organic base DIPEA to provide 1-indolyl-3,5,8-substituted γ-carbolines 3aa–ea in good yields. The γ-carbolines are fluorescent and exhibit anticancer activities against cervical, lung, breast, skin, and kidney cancer cells.
Synthesis of Indoles by Reductive Cyclization of Nitro Compounds Using Formate Esters as CO Surrogates
Ahmed Fouad, Manar,Ferretti, Francesco,Formenti, Dario,Milani, Fabio,Ragaini, Fabio
supporting information, p. 4876 - 4894 (2021/09/20)
Alkyl and aryl formate esters were evaluated as CO sources in the Pd- and Pd/Ru-catalyzed reductive cyclization of 2-nitrostyrenes to give indoles. Whereas the use of alkyl formates requires the presence of a ruthenium catalyst such as Ru3(CO)12, the reaction with phenyl formate can be performed by using a Pd/phenanthroline complex alone. Phenyl formate was found to be the most effective CO source and the desired products were obtained in excellent yields, often higher than those previously reported using pressurized CO. The reaction tolerates many functional groups, including sensitive ones like a free aldehydic group or a pendant pyrrole. Detailed experiments and kinetic studies allow to conclude that the activation of phenyl formate is base-catalyzed and that the metal doesn't play a role in the decarbonylation step. The reactions can be performed in a single thick-walled glass tube with as little as 0.2 mol-% palladium catalyst and even on a 2 g scale. The same protocol can be extended to other nitro compounds, affording different heterocycles.
Synthesis of pyrrolocarbazoles with N-substituted alkynyl-, alkylcyano- And alkylhydroxyl-groups
van der Westhuyzen, Alet E.,Hadjegeorgiou, Kathy,Green, Ivan R.,Pelly, Stephen C.,van Otterlo, Willem A.L.
, p. 129 - 147 (2021/01/20)
Due to their involvement in almost all stages of cellular life, kinase biomolecular catalysts have been linked to cancer development and, thus, remain attractive drug targets for cancer therapeutics. 6-(3-Hydroxypropyl)-, 6-(2-hydroxyethyl)-, 6-(2-propynyl)- and 6-(3’-propanenitrile)-pyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones were synthesized as potential small molecule EGFR kinase inhibitors. The pyrrolocarbazole compounds were synthesized by way of a Diels-Alder approach involving N-alkylated 2-vinyl-1H-indole and maleimide as starting materials followed by aromatization with MnO2.
Carbene-Catalyzed Enantioselective Aromatic N-Nucleophilic Addition of Heteroarenes to Ketones
Liu, Yonggui,Luo, Guoyong,Yang, Xing,Jiang, Shichun,Xue, Wei,Chi, Yonggui Robin,Jin, Zhichao
supporting information, p. 442 - 448 (2019/11/25)
The aromatic nitrogen atoms of heteroarylaldehydes are activated by carbene catalysts to react with ketone electrophiles. Multi-functionalized cyclic N,O-acetal products are afforded in good to excellent yields and optical purities. Our reaction involves the formation of an unprecedented aza-fulvene-type acylazolium intermediate. A broad range of N-heteroaromatic aldehydes and electron-deficient ketone substrates works effectively in this transformation. Several of the chiral N,O-acetal products afforded through this protocol exhibit excellent antibacterial activities against Ralstonia solanacearum (Rs) and are valuable in the development of novel agrichemicals for plant protection.
