90004-06-1Relevant articles and documents
Identification of thiophene-benzenesulfonamide derivatives for the treatment of multidrug-resistant tuberculosis
Batt, Sarah M.,Besra, Gurdyal S.,Fu, Lei,Huang, Haihong,Li, Gang,Lu, Yu,Qin, Rongfei,Wang, Bin,Wang, Pengxu,Wang, Yanan,Wu, Chengwei
, (2022/02/01)
A series of thiophene-benzenesulfonamide derivatives was designed and synthesized by exploring the structure-activity relationship of lead compounds 2,3-disubstituted thiophenes 25a and 297F as antituberculosis agents, which displayed potent antimycobacterial activity against drug-susceptible and clinically isolated drug-resistant tuberculosis. In particular, compound 17b, which had improved activity (minimum inhibitory concentration of 0.023 μg/mL) compared with the lead compounds, displayed good intracellular antimycobacterial activity in macrophages with a reduction of 1.29 log10 CFU. A druggability evaluation indicated that compound 17b had favorable hepatocyte stability, low cytotoxicity, and low hERG channel inhibition. Moreover, compound 17b exhibited modest in vivo efficacy in an acute mouse model of tuberculosis. In addition, the molecular docking study elucidated the binding mode of compound 17b in the active site of DprE1. Therefore, compound 17b may be a promising antituberculosis lead for further research.
Nickel-promoted oxidative domino Csp3-H/N-H bond double-isocyanide insertion reaction to construct pyrrolin-2-ones
Wen, Li-Rong,Wang, Ning-Ning,Du, Wu-Bo,Ma, Qiang,Zhang, Lin-Bao,Li, Ming
supporting information, p. 2895 - 2900 (2021/04/14)
The first nickel-catalyzed oxidative domino Csp3-H/N-H double isocyanide insertion reaction of acetamides with isocyanides has been developed for the synthesis of pyrrolin-2-one derivatives. A wide range of acetamides bearing various functional groups are compatible with this reaction system by utilizing Ni(acac)2as a catalyst. In this transformation, isocyanide could serve as a C1 connector and insert into the inactive Csp3-H bond, representing an effective way to construct heterocycles.
From cycloheptathiophene-3-carboxamide to oxazinone-based derivatives as allosteric HIV-1 ribonuclease H inhibitors
Massari, Serena,Corona, Angela,Distinto, Simona,Desantis, Jenny,Caredda, Alessia,Sabatini, Stefano,Manfroni, Giuseppe,Felicetti, Tommaso,Cecchetti, Violetta,Pannecouque, Christophe,Maccioni, Elias,Tramontano, Enzo,Tabarrini, Oriana
, p. 55 - 74 (2018/10/31)
The paper focussed on a step-by-step structural modification of a cycloheptathiophene-3-carboxamide derivative recently identified by us as reverse transcriptase (RT)-associated ribonuclease H (RNase H) inhibitor. In particular, its conversion to a 2-aryl-cycloheptathienoozaxinone derivative and the successive thorough exploration of both 2-aromatic and cycloheptathieno moieties led to identify oxazinone-based compounds as new anti-RNase H chemotypes. The presence of the catechol moiety at the C-2 position of the scaffold emerged as critical to achieve potent anti-RNase H activity, which also encompassed anti-RNA dependent DNA polymerase (RDDP) activity for the tricyclic derivatives. Benzothienooxazinone derivative 22 resulted the most potent dual inhibitor exhibiting IC50s of 0.53 and 2.90 μM against the RNase H and RDDP functions. Mutagenesis and docking studies suggested that compound 22 binds two allosteric pockets within the RT, one located between the RNase H active site and the primer grip region and the other close to the DNA polymerase catalytic centre.
A Novel Ketonitrile Synthesis by Palladium-Catalyzed Carbonylative Coupling Reactions of Amides with Arylboronic Acids
Mai, Wen-Peng,Liu, Yang,Sui, Hong-Dai,Xiao, Yong-Mei,Mao, Pu,Lu, Kui
supporting information, p. 7814 - 7819 (2019/12/24)
A novel, efficient, and simple procedure to synthesize diverse ketonitriles by palladium-catalyzed Suzuki coupling of amides through N–C cleavage has been developed. This procedure features mild conditions, a broad substrate scope, and easily prepared substrates, providing a simple and efficient access to a variety of ketonitriles.
Synthesis, cytotoxic characterization, and SAR study of imidazo[1,2-b]pyrazole-7-carboxamides
Demjén, András,Alf?ldi, Róbert,Angyal, Anikó,Gyuris, Márió,Hackler, László,Szebeni, Gábor J.,W?lfling, János,Puskás, László G.,Kanizsai, Iván
, (2018/07/13)
The synthesis and in vitro cytotoxic characteristics of new imidazo[1,2-b]pyrazole-7-carboxamides were investigated. Following a hit-to-lead optimization exploiting 2D and 3D cultures of MCF-7 human breast, 4T1 mammary gland, and HL-60 human promyelocytic leukemia cancer cell lines, a 67-membered library was constructed and the structure–activity relationship (SAR) was determined. Seven synthesized analogues exhibited sub-micromolar activities, from which compound 63 exerted the most significant potency with a remarkable HL-60 sensitivity (IC50 = 0.183 μM).
Exploring the cycloheptathiophene-3-carboxamide scaffold to disrupt the interactions of the influenza polymerase subunits and obtain potent anti-influenza activity
Desantis, Jenny,Nannetti, Giulio,Massari, Serena,Barreca, Maria Letizia,Manfroni, Giuseppe,Cecchetti, Violetta,Palù, Giorgio,Goracci, Laura,Loregian, Arianna,Tabarrini, Oriana
, p. 128 - 139 (2017/07/03)
With the aim to identify small molecules able to disrupt PA-PB1 subunits interaction of influenza virus (flu) RNA-dependent RNA polymerase, and based on previous structural and computational information, in this paper we have designed and synthesized a new series of cycloheptathiophene-3-carboxamide (cHTC) derivatives. Their biological evaluation led to highlight important structural insights along with new interesting compounds, such as the 2-hydroxybenzamido derivatives 29, 31, and 32, and the 4-aminophenyl derivative 54, which inhibited viral growth in the low micromolar range (EC50 = 0.18–1.2 μM) at no toxic concentrations (CC50 > 250 μM). This study permitted to obtain among the most potent anti-flu compounds within the PA-PB1 interaction inhibitors, confirming the cHTC scaffold as particularly suitable to achieve innovative anti-flu agents.
Ketenes from N-(2-Pyridyl)amides
Plüg, Carsten,Kanaani, Hussein,Wentrup, Curt
, p. 687 - 692 (2015/04/27)
Methoxycarbonylketene 4a, methoxycarbonyl(methyl)ketene 4b, chloroketene 4c, cyanoketene 4d, diphenylketene 4e, and 2-pyridylketene 4f have been generated by flash vacuum thermolysis of the corresponding 2-pyridylacetamide derivatives 3a-f and isolated in Ar matrices for FT-IR spectroscopic characterisation. The N-(2-pyridyl)-2-pyridylacetamide 3f yielded 2-pyridyl isocyanate in addition to 2-pyridylketene.
Designing, synthesis, and characterization of some novel coumarin derivatives as probable anticancer drugs
Manidhar, Darla Mark,Kesharwani, Rajesh Kumar,Reddy, N. Bakthavatchala,Reddy, C. Suresh,Misra, Krishna
, p. 4146 - 4157 (2013/09/02)
Coumarin is a naturally occurring oxygen heterocyclic having multifarious medicinal properties, hence used as a lead compound for designing new potent analogs. Based on the X-ray crystal structure of complexes of inhibitors containing coumarin nucleus with human NAD(P)H:quinone oxidoreductase-1 and human phosphodiesterase 4B enzymes, some novel coumarin derivatives have been designed as probable inhibitors specifically for pancreatic cancer. These two enzymes are overexpressed in various tumors, the former specifically in pancreatic cancer. The computational analysis by e-pharmacophore and docking studies suggested that specific groups at position 8 of 4-methyl-7- hydroxycoumarin have anticancer activity against skin cancer in mice and can enhance the anti-tumor activity. The chemical syntheses of 4-methyl-7- hydroxycoumarin and its 8-formyl derivative were carried out using Pechmann's condensation followed by Duffs reaction. Treatment of the 8-formyl derivative with nine different N,N-di substituted cyanoacetamides in the presence of piperidine afforded the corresponding nine new 8-substituted-4-methyl-7- hydroxycoumarin derivatives. These compounds were characterized by IR, 1H, 13C NMR, mass spectra and elemental analysis. Intriguingly, molecular docking suggested a remarkable binding pose for all the nine coumarin derivatives vis-a-vis coumarin itself, opening further options for designing inhibitors for tumor suppression. From the docking simulation study, it was concluded that the derived coumarin derivatives are active against more than one proteins and most importantly addition of substituents at the 8th position of 4-methyl-7-hydroxycoumarin support the possibility of new coumarin derivatives having comparatively higher binding affinity and therefore more potent inhibitors.
Rapid microwave-assisted solution phase synthesis of substituted 2-pyridone libraries
Gorobets, Nikolay Yu.,Yousefi, Behrooz H.,Belaj, Ferdinand,Kappe, C. Oliver
, p. 8633 - 8644 (2007/10/03)
2-Pyridone and 2-quinolone analogues are well-known biologically active heterocyclic scaffolds. Libraries of 3,5,6-substituted 2-pyridone derivatives are generated by rapid microwave assisted solution phase methods using a one-pot, two-step protocol. The three-component condensation of CH-acidic carbonyl compounds, N,N-dimethylformamide dimethylacetal and methylene active nitriles, leads to 2-pyridones and fused analogues in moderate to good overall yields and high purities. The proposed mechanism of this novel multi-component reaction, structure elucidation of products and intermediates are discussed.
SYNTHESIS OF N-(2-PYRIDYL)CYANOACETAMIDES AND 4-AMINO-2H-PYRIDOPYRIMIDIN-2-ONES FROM ETHYL CYANOACETATE AND 2-AMINOPYRIDINE
Dorokhov, V. A.,Baranin, S. V.,Dib, A.,Bogdanov, V. S.,Yakovlev, I. P.,et al.
, p. 1918 - 1923 (2007/10/02)
The reaction of 2-aminopyridine and 2-aminopicolines with ethyl cyanoacetate under high pressures results in the formation of 4-amino-4H-pyridopyrimidin-2-ones.Depending on the structure of the initial pyridine base, heating of a mixture of the above reagents under low vacuum gives either the same products or their isomeric N-(2-pyridyl)cyanoacetamides.The mutual transformations of the synthesized isomers were studied; it was found that cyanoacetamides are readily cyclized by the action of alcoholic solution of HCl into pyridopyrimidin-2-ones, while the latter, during sublimation or heating in DMSO, undergo opening of the pyrimidine ring.
