26286-54-4Relevant academic research and scientific papers
Synthesis of indolo- And pyrrolo[1,2-: a] quinoxalinones through a palladium-catalyzed oxidative carbonylation of the C 2 position of indole
Chandrasekhar, Attoor,Sankararaman, Sethuraman
supporting information, p. 1612 - 1622 (2020/03/06)
A methodology that involves the Pd-catalyzed direct C(sp2)-H bond carbonylation of the C2 position of indole has been introduced for the synthesis of indolo[1,2-a]quinoxalin-6(5H)-ones. The methodology developed herein was used for the synthesis of pyrrolo[1,2-a]quinoxalin-4(5H)-ones. The reaction of N-substituted 2-(1H-indol-1-yl)anilines or 2-(1H-pyrrol-1-yl)anilines and carbon monoxide in the presence of Pd(OCOCF3)2 as a catalyst and Cu(OAc)2 as an oxidant in toluene at 80 °C forms the corresponding quinoxalinones as exclusive products in good yields. The catalytically active C-H activated intermediate Pd complex was isolated and characterized for the first time which on exposure to CO gas in toluene at 80 °C gave the corresponding quinoxalinone derivative. On the basis of isolation of the intermediate, a possible mechanism has been proposed for the C-H activated direct carbonylative annulation of 2-(5-methoxy-1H-indol-1-yl)-N,4-dimethylaniline.
KI-Mediated One-Pot Transition-Metal-Rree Synthesis of 4-Phenylpyrrolo[1,2-a]quinoxalines
Li, Shichen,Xie, Caixia,Chu, Xianglong,Dai, Zhen,Feng, Lei,Ma, Chen
supporting information, p. 4950 - 4956 (2020/08/10)
An efficient and eco-friendly method for the synthesis of pyrrolo[1,2-a]quinoxalines is presented. Compared to previous methods, this protocol is transition-metal-free and only potassium iodide is required. A series of substituted 4-phenylpyrrolo[1,2-a]quinoxalines are obtained in moderate to good yields.
Fragment-Based Discovery of a Qualified Hit Targeting the Latency-Associated Nuclear Antigen of the Oncogenic Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8
Kirsch, Philine,Jakob, Valentin,Oberhausen, Kevin,Stein, Saskia C.,Cucarro, Ivano,Schulz, Thomas F.,Empting, Martin
, p. 3924 - 3939 (2019/05/06)
The latency-associated nuclear antigen (LANA) is required for latent replication and persistence of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8. It acts via replicating and tethering the virus episome to the host chromatin and exerts other functions. We conceived a new approach for the discovery of antiviral drugs to inhibit the interaction between LANA and the viral genome. We applied a biophysical screening cascade and identified the first LANA binders from small, structurally diverse compound libraries. Starting from a fragment-sized scaffold, we generated optimized hits via fragment growing using a dedicated fluorescence-polarization-based assay as the structure-activity-relationship driver. We improved compound potency to the double-digit micromolar range. Importantly, we qualified the resulting hit through orthogonal methods employing EMSA, STD-NMR, and MST methodologies. This optimized hit provides an ideal starting point for subsequent hit-to-lead campaigns providing evident target-binding, suitable ligand efficiencies, and favorable physicochemical properties.
Optimization of Drug Candidates That Inhibit the D-Loop Activity of RAD51
Budke, Brian,Tueckmantel, Werner,Miles, Kelsey,Kozikowski, Alan P.,Connell, Philip P.
supporting information, p. 1031 - 1040 (2019/04/30)
RAD51 is the central protein in homologous recombination (HR) repair, where it first binds ssDNA and then catalyzes strand invasion via a D-loop intermediate. Additionally, RAD51 plays a role in faithful DNA replication by protecting stalled replication forks; this requires RAD51 to bind DNA but may not require the strand invasion activity of RAD51. We previously described a small-molecule inhibitor of RAD51 named RI(dl)-2 (RAD51 inhibitor of D-loop formation #2, hereafter called 2 h), which inhibits D-loop activity while sparing ssDNA binding. However, 2 h is limited in its ability to inhibit HR in vivo, preventing only about 50 % of total HR events in cells. We sought to improve upon this by performing a structure–activity relationship (SAR) campaign for more potent analogues of 2 h. Most compounds were prepared from 1-(2-aminophenyl)pyrroles by forming the quinoxaline moiety either by condensation with aldehydes, then dehydrogenation of the resulting 4,5-dihydro intermediates, or by condensation with N,N′-carbonyldiimidazole, chlorination, and installation of the 4-substituent through Suzuki–Miyaura coupling. Many analogues exhibited enhanced activity against human RAD51, but in several of these compounds the increased inhibition was due to the introduction of dsDNA intercalation activity. We developed a sensitive assay to measure dsDNA intercalation, and identified two analogues of 2 h that promote complete HR inhibition in cells while exerting minimal intercalation activity.
Fragment-Based Discovery of a Qualified Hit Targeting the Latency-Associated Nuclear Antigen of the Oncogenic Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8
Kirsch, Philine,Jakob, Valentin,Oberhausen, Kevin,Stein, Saskia C.,Cucarro, Ivano,Schulz, Thomas F.,Empting, Martin
, (2019/05/01)
The latency-associated nuclear antigen (LANA) is required for latent replication and persistence of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8. It acts via replicating and tethering the virus episome to the host chromatin and exerts other functions. We conceived a new approach for the discovery of antiviral drugs to inhibit the interaction between LANA and the viral genome. We applied a biophysical screening cascade and identified the first LANA binders from small, structurally diverse compound libraries. Starting from a fragment-sized scaffold, we generated optimized hits via fragment growing using a dedicated fluorescence-polarization-based assay as the structure-activity-relationship driver. We improved compound potency to the double-digit micromolar range. Importantly, we qualified the resulting hit through orthogonal methods employing EMSA, STD-NMR, and MST methodologies. This optimized hit provides an ideal starting point for subsequent hit-to-lead campaigns providing evident target-binding, suitable ligand efficiencies, and favorable physicochemical properties.
A catalytic intramolecular nitrene insertion into a copper(i)-N-heterocyclic carbene bond yielding fused nitrogen heterocycles
Fauché, Kévin,Nauton, Lionel,Jouffret, Laurent,Cisnetti, Federico,Gautier, Arnaud
supporting information, p. 2402 - 2405 (2017/02/23)
N-(2-Azidophenyl)azolium salts were easily prepared and reacted with copper(i) under conditions allowing the formation of NHC complexes. Under these conditions, the formation of benzimidazo-fused heterocycles occurred under catalytic, efficient and very mild conditions. This reaction is proposed to proceed via dinitrogen elimination and imido/nitrene-NHC cyclization.
Dimethyl Sulfoxide Involved One-Pot Synthesis of Quinoxaline Derivatives
Xie, Caixia,Zhang, Zeyuan,Li, Danyang,Gong, Jian,Han, Xushuang,Liu, Xuan,Ma, Chen
, p. 3491 - 3499 (2017/04/11)
An efficient, green, and novel method for the synthesis of N-heterocycle-fused quinoxalines is reported herein. Dimethyl sulfoxide was used as both a reactant and a solvent in this reaction. A wide range of products in moderate to excellent yields were obtained, including pyrrolo[1,2-a]quinoxalines, indolo[1,2-a]quinoxalines, 1H-pyrrolo[3,2-c]quinolines, and benzo[4,5]imidazo[1,2-c]quinazolines.
3-(Diphenylphosphino)propanoic acid: An efficient ligand for the Cu-catalyzed N-arylation of imidazoles and 1H-pyrazole with aryl halides
Liu, Ya-Shuai,Liu, Yan,Ma, Xiao-Wei,Liu, Ping,Xie, Jian-Wei,Dai, Bin
, p. 775 - 778 (2014/06/09)
3-(Diphenylphosphino)propanoic acid (L2) has proved to be an efficient ligand for the copper-catalyzed CN coupling reactions. N-arylation of imidazoles with aryl iodides catalyzed by CuCl/L2 was smoothly carried out in DMSO at 100 °C with a yield up to 98%. N-arylation of 1H-pyrazole with aryl iodides and bromides catalyzed by Cu(OAc)2/L2 in 1,4-dioxane also gave the corresponding products with yields of 40%-98%.
A facile one-step approach for the synthesis of uniform spherical Cu/Cu2O nano- and microparticles with high catalytic activity in the Buchwald-Hartwig amination reaction
Bhosale, Manohar A.,Bhanage, Bhalchandra M.
, p. 15122 - 15130 (2014/04/17)
In the present work, we have developed a rapid, one step, calcination-free protocol for the synthesis of uniform spherical Cu/Cu2O nano/microparticles (NMPs). The synthesis of Cu/Cu2O NMPs was achieved by microwave irradiation of copper acetate as a precursor and 1,4-butanediol as a solvent in a few minutes. The prepared Cu/Cu2O NMPs gave 100% yield of uniform spherical morphology. 1,4-Butanediol plays a crucial role in reactions such as a solvent, reactant, stabilizer and capping agent which control the crystal morphology. The resultant product was characterized with the help of different techniques such as XRD, FEG-SEM, EDS, TEM, FT-IR, TPR, DSC-TGA, XPS and BET surface area analysis. The results confirm that the Cu/Cu2O NMPs had good crystallinity and were essentially pure. This is a simple, faster, inexpensive and additive-free protocol for synthesis of nanocrystalline Cu/Cu2O compared to the conventional method. These Cu/Cu2O NMPs showed excellent catalytic activity in the Buchwald-Hartwig amination coupling reaction. Notably the reaction does not require any ligand source, and requires low catalyst loading, and low temperature with catalyst recyclability. the Partner Organisations 2014.
Synthesis of highly functionalized polycyclic quinoxaline derivatives using visible-light photoredox catalysis
He, Zhi,Bae, Minwoo,Wu, Jie,Jamison, Timothy F.
supporting information, p. 14451 - 14455 (2015/02/19)
A mild and facile method for preparing highly functionalized pyrrolo[1,2-a]quinoxalines and other nitrogenrich heterocycles, each containing a quinoxaline core or an analogue thereof, has been developed. The novel method features a visible-light-induced decarboxylative radical coupling of ortho-substituted arylisocyanides and radicals generated from phenyliodine(III) dicarboxylate reagents and exhibits excellent functional group compatibility. A wide range of quinoxaline heterocycles have been prepared. Finally, a telescoped preparation of these polycyclic compounds by integration of the in-line isocyanide formation and photochemical cyclization has been established in a three-step continuousflow system.
