3388-98-5Relevant academic research and scientific papers
Pyrrolo[1,2-a]quinoxalines: Insulin Mimetics that Exhibit Potent and Selective Inhibition against Protein Tyrosine Phosphatase 1B
García-Marín, Javier,Griera, Mercedes,Sánchez-Alonso, Patricia,Di Geronimo, Bruno,Mendicuti, Francisco,Rodríguez-Puyol, Manuel,Alajarín, Ramón,de Pascual-Teresa, Beatriz,Vaquero, Juan J.,Rodríguez-Puyol, Diego
supporting information, p. 1788 - 1801 (2020/09/15)
PTP1B dephosphorylates insulin receptor and substrates to modulate glucose metabolism. This enzyme is a validated therapeutic target for type 2 diabetes, but no current drug candidates have completed clinical trials. Pyrrolo[1,2-a]quinoxalines substituted at positions C1–C4 and/or C7–C8 were found to be nontoxic to cells and good inhibitors in the low- to sub-micromolar range, with the 4-benzyl derivative being the most potent inhibitor (0.24 μm). Some analogues bearing chlorine atoms at C7 and/or C8 kept potency and showed good selectivity compared to TCPTP (selectivity index '40). The most potent inhibitors behaved as insulin mimetics by increasing glucose uptake. The 4-benzyl derivative inhibited insulin receptor substrate 1 and AKT phosphorylation. Molecular docking and molecular dynamics simulations supported a putative binding mode for these compounds to the allosteric α3/α6/α7 pocket, but inconsistent results in enzyme inhibition kinetics were obtained due to the high tendency of these inhibitors to form stable aggregates. Computational calculations supported the druggability of inhibitors.
NBE-Controlled Palladium-Catalyzed Interannular Selective C-H Silylation: Access to Divergent Silicon-Containing 1,1′-Biaryl-2-Acetamides
Li, Wenguang,Chen, Wenqi,Zhou, Bang,Xu, Yankun,Deng, Guobo,Liang, Yun,Yang, Yuan
, p. 2718 - 2722 (2019/04/16)
A novel palladium-catalyzed interannular selective C-H silylation of 1,1′-biaryl-2-acetamides is described. The combination of palladium catalyst with copper oxidant enables meta- or ortho-selective C-H silylation by employing hexamethyldisilane as a trimethylsilyl source, which relies on the control of NBE derivatives as a switch, thus providing straightforward access to divergent silicon-containing 1,1′-biaryl-2-acetamides.
Iridium-catalyzed Asymmetric Hydrogenation of Polycyclic Pyrrolo/Indolo[1,2-a]quinoxalines and Phenanthridines
Hu, Shu-Bo,Zhai, Xiao-Yong,Shen, Hong-Qiang,Zhou, Yong-Gui
supporting information, p. 1334 - 1339 (2018/02/06)
Owing to the dehydrogenative rearomatization of hydrogenation product and poisoning effect of nitrogen atom, asymmetric hydrogenation of polycyclic nitrogen-containing heteroaromatics is still a great challenge. Herein, through in situ protection of hydro
Harnessing the pyrroloquinoxaline scaffold for FAAH and MAGL interaction: Definition of the structural determinants for enzyme inhibition
Brindisi, Margherita,Brogi, Simone,Maramai, Samuele,Grillo, Alessandro,Borrelli, Giuseppe,Butini, Stefania,Novellino, Ettore,Allarà, Marco,Ligresti, Alessia,Campiani, Giuseppe,Di Marzo, Vincenzo,Gemma, Sandra
, p. 64651 - 64664 (2016/07/23)
This paper describes the development of piperazine and 4-aminopiperidine carboxamides/carbamates supported on a pharmacogenic pyrroloquinoxaline scaffold as inhibitors of the endocannabinoid catabolizing enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). Structure-activity relationships and molecular modelling studies allowed the definition of the structural requirements for dual FAAH/MAGL inhibition and led to the identification of a small set of derivatives (compounds 5e, i, k, m) displaying a balanced inhibitory profile against both enzymes, with compound 5m being the frontrunner of the subset. Favorable calculated physico-chemical properties suggest further investigation for specific analogues.
Synthesis, analytical behaviour and biological evaluation of new 4-substituted pyrrolo[1,2-a]quinoxalines as antileishmanial agents
Guillon, Jean,Forfar, Isabelle,Mamani-Matsuda, Maria,Desplat, Vanessa,Saliege, Marion,Thiolat, Denis,Massip, Stephane,Tabourier, Anais,Leger, Jean-Michel,Dufaure, Benoit,Haumont, Gilbert,Jarry, Christian,Mossalayi, Djavad
, p. 194 - 210 (2008/02/01)
An original series of 4-substituted pyrrolo[1,2-a]quinoxaline derivatives, new structural analogues of Galipea species quinoline alkaloids, was synthesized from various substituted 2-nitroanilines via multistep heterocyclizations and tested for in vitro antiparasitic activity upon Leishmania amazonensis and Leishmania infantum strains. Structure-activity relationships enlighten the importance of the 4-substituted alkenyl side chain on the pyrrolo[1,2-a]quinoxaline moiety to modulate the antileishmanial activity.
